Publications by authors named "Stefano Muzzarelli"

39 Publications

Predicting hospitalization and mortality in patients with heart failure: The BARDICHE-index.

Int J Cardiol 2017 Jan 9;227:901-907. Epub 2016 Nov 9.

Department of Cardiology, CARIM; Maastricht University Medical Centre + (MUMC+), Maastricht, The Netherlands; Department of Cardiology, University Hospital, Basel, Switzerland.

Background: Prediction of events in chronic heart failure (CHF) patients is still difficult and available scores are often complex to calculate. Therefore, we developed and validated a simple-to-use, multidimensional prognostic index for such patients.

Methods: A theoretical model was developed based on known prognostic factors of CHF that are easily obtainable: Body mass index (B), Age (A), Resting systolic blood pressure (R), Dyspnea (D), N-termInal pro brain natriuretic peptide (NT-proBNP) (I), Cockroft-Gault equation to estimate glomerular filtration rate (C), resting Heart rate (H), and Exercise performance using the 6-min walk test (E) (the BARDICHE-index). Scores were given for all components and added, the sum ranging from 1 (lowest value) to 25 points (maximal value), with estimated risk being highest in patients with highest scores. Scores were categorized into three groups: a low (≤8 points); medium (9-16 points), or high (>16 points) BARDICHE-score. The model was validated in a data set of 1811 patients from two prospective CHF-cohorts (median follow-up 887days). The primary outcome was 5-year all-cause survival. Secondary outcomes were 5-year survival without all-cause hospitalization and 5-year survival without CHF-related hospitalization.

Results: There were significant differences between BARDICHE-risk groups for mortality (hazard ratio=3.63 per BARDICHE-group, 95%-CI 3.10-4.25), mortality or all-cause hospitalization (HR=2.00 per BARDICHE-group, 95%-CI 1.83-2.19), and mortality or CHF-related hospitalization (HR=3.43 per BARDICHE-group, 95%-CI 3.01-3.92; all P<10-50). Outcome was predicted independently of left ventricular ejection fraction (LVEF) and gender.

Conclusions: The BARDICHE-index is a simple multidimensional prognostic tool for patients with CHF, independently of LVEF.
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http://dx.doi.org/10.1016/j.ijcard.2016.11.122DOI Listing
January 2017

Predictors of disagreement between prospectively ECG-triggered dual-source coronary computed tomography angiography and conventional coronary angiography.

Eur J Radiol 2016 Jun 22;85(6):1138-46. Epub 2016 Mar 22.

Division of Cardiology, Fondazione Cardiocentro Ticino, Via Tesserete 48, CH-6900 Lugano, Switzerland. Electronic address:

Aims: To identify causes of misinterpretation in second generation, dual-source coronary computed tomography angiography (CCTA).

Methods: A retrospective re-interpretation was performed on 100 consecutive CCTA studies, previously performed with a 2×128 slice dual-source CT. Results were compared with coronary angiography (CA). CCTA and CA images were interpreted by 2 independent readers. At CCTA vessel diameter, image quality, plaque characteristics and localization (bifurcation vs. non) were described for all segments. Finally, aortic contrast-to-noise ratio (CNR) and the total Agatston calcium score were quantified. Agreement between CCTA and CA was assessed with the Kappa statistic after categorizing the stenosis severity at significant (≥50%) and critical (≥70%) cut-offs, and independent predictors of disagreement were determined by multivariable logistic regression, including patient characteristics such as body mass index (BMI), heart rate (HR), age and gender.

Results: Per-segment sensitivity and specificity at ≥50% and ≥70% stenosis was of 83-95%, and 73-97%, respectively. There was a substantial agreement between CCTA and CA (kappa-50%=0.78, SE=0.03; kappa-70%=0.72, SE=0.03). Worse motion-related quality score, smaller vessel diameter, calcification within the segment of interest and LAD location were independent predictors of disagreement at 50% stenosis. The same factors, excluded LAD location, in addition to bifurcation-location of the coronary lesion predicted misdiagnosis at 70% stenosis. HR per se and BMI did not predict disagreement.

Conclusion: According to the literature a substantial agreement between CCTA and CA was found. However, discrepancies exist and are mainly related with motion-related degradation of image quality, specific vessel anatomy and plaque characteristics. Awareness of such potential limitations may help guiding interpretation of CCTA.
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http://dx.doi.org/10.1016/j.ejrad.2016.03.021DOI Listing
June 2016

An in-silico analysis of the effect of heart position and orientation on the ECG morphology and vectorcardiogram parameters in patients with heart failure and intraventricular conduction defects.

J Electrocardiol 2015 Jul-Aug;48(4):617-25. Epub 2015 May 8.

Center for Computational Medicine in Cardiology, Institute of Computational Science, Università della Svizzera italiana, Lugano, Switzerland; Division of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland.

Aim: The aim of this study was to investigate the influence of geometrical factors on the ECG morphology and vectorcardiogram (VCG) parameters.

Methods: Patient-tailored models based on five heart-failure patients with intraventricular conduction defects (IVCDs) were created. The heart was shifted up to 6 cm to the left, right, up, and down and rotated ±30° around the anteroposterior axis. Precordial electrodes were shifted 3 cm down.

Results: Geometry modifications strongly altered ECG notching/slurring and intrinsicoid deflection time. Maximum VCG parameter changes were small for QRS duration (-6% to +10%) and QRS-T angle (-6% to +3%), but considerable for QRS amplitude (-36% to +59%), QRS area (-37% to +42%), T-wave amplitude (-41% to +36%), and T-wave area (-42% to +33%).

Conclusion: The position of the heart with respect to the electrodes is an important factor determining notching/slurring and voltage-dependent parameters and therefore must be considered for accurate diagnosis of IVCDs.
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http://dx.doi.org/10.1016/j.jelectrocard.2015.05.004DOI Listing
March 2016

Fulminant lymphocytic myocarditis mimicking ST-elevation myocardial infarction.

Eur Heart J 2015 Sep 20;36(33):2227. Epub 2015 May 20.

Department of Cardiology, CardioCentroTicino, via Tesserete 48, Lugano 6900, Switzerland.

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http://dx.doi.org/10.1093/eurheartj/ehv166DOI Listing
September 2015

Low-intensity late gadolinium enhancement predominates in hypertrophic cardiomyopathy.

Clin Imaging 2015 May-Jun;39(3):432-6. Epub 2015 Jan 14.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Ave., M-391, San Francisco, CA 94143-0628.

Aim: Assess the extent of low- versus high-intensity late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM).

Methods: Low- versus high-intensity LGE indexed volumes in 19 HCM patients were compared to 23 myocardial infarction (MI) patients.

Results: Total, low-, and high-intensity LGE volumes in HCM vs. MI were 7.6ml/m(2), 4.7, and 2.4 vs. 11.2, 2.5, and 7.1, respectively. Total LGE volume did not differ (P=.13), though low- and high-intensity did (P=.05, .004). 67% versus 26% of all LGE was low-intensity in HCM versus MI (P<.001).

Conclusions: LGE in HCM is predominantly low-intensity, so a low threshold may be the most appropriate.
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http://dx.doi.org/10.1016/j.clinimag.2015.01.001DOI Listing
November 2015

Three-dimensional transesophageal echocardiography in degenerative mitral regurgitation.

J Am Soc Echocardiogr 2015 Apr 14;28(4):437-48. Epub 2015 Feb 14.

Dipartimento di Cardiologia, Fondazione Cardiocentro Ticino, Lugano, Switzerland.

The morphology of mitral valve (MV) prolapse and flail may be extremely variable, with dominant and secondary dynamic lesions. Any pathologic valve appears unique and different from any other. Three-dimensional (3D) transesophageal echocardiography is a powerful tool to evaluate the geometry, dynamics, and function of the MV apparatus and may be of enormous value in helping surgeons perform valve repair procedures. Indeed, in contrast to the surgical view, 3D transesophageal echocardiography can visualize MV prolapse and flail in motion and from different perspectives. The purpose of this special article is not to provide a comprehensive review of degenerative MV disease but rather to illustrate different types of mitral prolapse and flail as they appear from multiple 3D transesophageal echocardiographic perspectives using a series of clinical scenarios. Because in everyday practice, 3D transesophageal echocardiographic images of MV prolapse and flail are usually observed in motion, each scenario is accompanied by several videos. Finally, the authors provide for each scenario a brief description of the surgical techniques that are usually performed at their institution.
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http://dx.doi.org/10.1016/j.echo.2015.01.006DOI Listing
April 2015

Differential prognostic impact of resting heart rate in older compared with younger patients with chronic heart failure--insights from TIME-CHF.

J Card Fail 2015 Apr 7;21(4):347-54. Epub 2015 Jan 7.

Department of Cardiology, University Hospital, Basel, Switzerland; Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.

Background: There is little information regarding the prognostic role of resting heart rate (HR) in older compared with younger patients with chronic heart failure (HF).

Methods And Results: In patients enrolled in the Trial of Intensified Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) with sinus rhythm, effects of baseline HR (≥70 vs <70 beats/min [bpm]) on 18-month outcomes were compared between older (≥75 years; n = 186) and younger (<75 years; n = 141) patients. Older patients with lower (61 ± 6 bpm) and higher (83 ± 9 bpm) HR had similar left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and survival and HF hospitalization-free survival. In contrast, younger patients with higher HR (81 ± 7 bpm) had higher NT-proBNP and NYHA functional class, lower LVEF, and a higher risk of death (hazard ratio 4.01 [95% confidence interval (CI) 1.17 -13.69]; P = .02) and death or HF hospitalization (hazard ratio 2.35 [95% CI 1.01-5.50]; P = .04) than those with lower HR (62 ± 5 bpm), with the association between higher HR and survival remaining significant after adjustment for NYHA functional class, LVEF, and NT-proBNP.

Conclusions: In contrast to HF patients aged <75 years, we found no association between HR and worse outcomes in HF patients aged ≥75 years.
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http://dx.doi.org/10.1016/j.cardfail.2014.12.014DOI Listing
April 2015

Patient-specific modelling of cardiac electrophysiology in heart-failure patients.

Europace 2014 Nov;16 Suppl 4:iv56-iv61

Center for Computational Medicine in Cardiology, Faculty of Informatics, Università della Svizzera italiana, Via Giuseppe Buffi 13, 6904 Lugano, Switzerland Division of Cardiology, Fondazione Cardiocentro Ticino, 6904 Lugano, Switzerland.

Aims: Left-ventricular (LV) conduction disturbances are common in heart-failure patients and a left bundle-branch block (LBBB) electrocardiogram (ECG) type is often seen. The precise cause of this pattern is uncertain and is probably variable between patients, ranging from proximal interruption of the left bundle branch to diffuse distal conduction disease in the working myocardium. Using realistic numerical simulation methods and patient-tailored model anatomies, we investigated different hypotheses to explain the observed activation order on the LV endocardium, electrogram morphologies, and ECG features in two patients with heart failure and LBBB ECG.

Methods And Results: Ventricular electrical activity was simulated using reaction-diffusion models with patient-specific anatomies. From the simulated action potentials, ECGs and cardiac electrograms were computed by solving the bidomain equation. Model parameters such as earliest activation sites, tissue conductivity, and densities of ionic currents were tuned to reproduce the measured signals. Electrocardiogram morphology and activation order could be matched simultaneously. Local electrograms matched well at some sites, but overall the measured waveforms had deeper S-waves than the simulated waveforms.

Conclusion: Tuning a reaction-diffusion model of the human heart to reproduce measured ECGs and electrograms is feasible and may provide insights in individual disease characteristics that cannot be obtained by other means.
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http://dx.doi.org/10.1093/europace/euu257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217520PMC
November 2014

Late acute coronary syndrome 9 months after uneventful transcatheter aortic valve replacement.

Eur Heart J 2015 Feb 21;36(6):376. Epub 2014 Oct 21.

Cardiocentro Ticino, Lugano, Switzerland

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http://dx.doi.org/10.1093/eurheartj/ehu413DOI Listing
February 2015

Reduction of ST-elevation myocardial infarction in Canton Ticino (Switzerland) after smoking bans in enclosed public places--No Smoke Pub Study.

Eur J Public Health 2015 Apr 3;25(2):195-9. Epub 2014 Jun 3.

1 Department of Cardiology, Ospedale San Giovanni (EOC), Bellinzona, Switzerland.

Background: Second-hand smoke increases the risk of acute myocardial infarction. Canton Ticino (CT) first introduced a smoking ban in public places in 2007. This offered the opportunity to assess the long-term impact of a smoking ban on the incidence of ST-elevation myocardial infarctions (STEMI) compared with a population where the law was not yet implemented.

Methods: We assessed the incidence of STEMI hospitalizations per 100 000 inhabitants both during 3 years before and after the ban application in CT and in Canton Basel City (CBC), where this law was not yet applied. Data were obtained from the codified hospital registry (ICD-10 codes).

Results: In CT, the mean incidence of STEMI admissions during the 3 pre-ban years (123.7) was significantly higher than the incidence of admissions in each of the 3 post-ban years (92.9, 101.6 and 89.6 respectively; P <.024). Analysing population subsets, a post-ban reduction was observed among ≥65-year-old people of both sexes in each of the 3 post-ban years and in the <65-year age group during the first post-ban year (P = 0.02). Conversely, the mean incidence of STEMI hospitalizations in CBC (92.4) didn't change significantly in each of the 3 post-ban years (83.9, 83.3 and 79.5, P = NS) during the same period. However, a significant long-term reduction in STEMI admissions was observed in CBC among the male group with ≥65 years (P < 0.01).

Conclusion: Our work suggests a significant impact of the smoke-free policy on the number of annual STEMI. Specific population subsets (i.e. ≥65-year-old females) were particularly affected by the smoking ban, showing a significant reduction in STEMI hospitalizations.
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http://dx.doi.org/10.1093/eurpub/cku067DOI Listing
April 2015

3D TEE during catheter-based interventions.

JACC Cardiovasc Imaging 2014 Mar;7(3):292-308

Division of Cardiology, Cardiocentro Ticino, Lugano, Switzerland.

Guidance of catheter-based procedures is performed using fluoroscopy and 2-dimensional transesophageal echocardiography (TEE). Both of these imaging modalities have significant limitations. Because of its 3-dimensional (3D) nature, 3D TEE allows visualizing the entire scenario in which catheter-based procedures take place (including long segments of catheters, tips, and the devices) in a single 3D view. Despite these undeniable advantages, 3D TEE has not yet gained wide acceptance among most interventional cardiologists and echocardiographists. One reason for this reluctance is probably the absence of standardized approaches for obtaining 3D perspectives that provide the most comprehensive information for any single step of any specific procedure. Therefore, the purpose of this review is to describe what we believe to be the most useful 3D perspectives in the following catheter-based percutaneous interventions: transseptal puncture; patent foramen ovale/atrial septal defect closure; left atrial appendage occlusion; mitral valve repair; and closure of paravalvular leaks.
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http://dx.doi.org/10.1016/j.jcmg.2013.10.012DOI Listing
March 2014

Interaction between pulmonary hypertension and diastolic dysfunction in an elderly heart failure population.

J Card Fail 2014 Feb 18;20(2):98-104. Epub 2013 Dec 18.

Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands; Division of Cardiology, University Hospital Basel, Basel, Switzerland.

Background: Pulmonary hypertension due to left heart disease is very common. Our aim was to investigate the relationship of the severity of left ventricular diastolic dysfunction with precapillary and postcapillary pulmonary hypertension (PH) in an elderly heart failure (HF) population.

Methods And Results: A post hoc analysis of the Trial of Intensified Medical Therapy in Elderly Patients With Congestive Heart Failure data was done. Baseline transthoracic echocardiography was used to categorize diastolic function, estimate pulmonary artery pressure and pulmonary capillary wedge pressure, and calculate the transpulmonary pressure gradient (TPG). Among 392 HF patients, PH was present in 31% of patients with grade 1, in 37% of patients with grade 2, and in 65% of patients with grade 3 diastolic dysfunction; 54% of all HF patients with PH had a TPG >12 mm Hg, suggesting not only a postcapillary but also an additional precapillary component of PH. Survival was not related to the severity of diastolic dysfunction, but was worse in patients with PH (hazard ratio 1.63, 95% confidence interval 1.07-2.51; P = .024).

Conclusions: Our data indicate that HF patients with even mild diastolic dysfunction often have PH. Echocardiographic assessment suggest that the presence of PH might not simply be due to increased PCWP, but in part due to a precapillary component.
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http://dx.doi.org/10.1016/j.cardfail.2013.12.010DOI Listing
February 2014

Imaging-based right-atrial anatomy by computed tomography, magnetic resonance imaging, and three-dimensional transoesophageal echocardiography: correlations with anatomic specimens.

Eur Heart J Cardiovasc Imaging 2013 Dec 12;14(12):1123-31. Epub 2013 Sep 12.

Division of Cardiology, Fondazione Cardiocentro Ticino, Via Tesserete 48, CH-6900 Lugano, Switzerland.

Nowadays computed tomography, cardiac magnetic resonance imaging, and tridimensional transoesophageal echocardiography provide anatomic images of right-atrial structures with an impressive richness of anatomical details. It is therefore surprising that these techniques are not routinely used as complementary tools in teaching anatomy. This review aims to fill this gap showing the normal anatomy of right atrium as displayed by these sophisticated imaging techniques. A better understanding of right-atrial anatomy is crucial for the treatment of primary right-atrium electrical disorders as well as for catheter-based interventions for structural heart disease. The success of these procedures is, in fact, related to an accurate anatomical pre-procedural assessment. In this review, we describe the normal anatomy and variants of those right-atrial structures relevant for both ablationists and interventionalists.
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http://dx.doi.org/10.1093/ehjci/jet081DOI Listing
December 2013

Cardiovascular MR imaging after surgical correction of tetralogy of Fallot: approach based on understanding of surgical procedures.

Radiographics 2013 Jul-Aug;33(4):1037-52

Department of Radiology, University Hospital of California, Box 0628, 505 Parnassus Ave, Room L-325A, San Francisco, CA 94143-0252, USA.

Tetralogy of Fallot (TOF) is one of the most common congenital heart diseases for which patients are referred for postoperative magnetic resonance (MR) imaging evaluation. The most common surgical procedures for TOF repair include infundibulectomy, transannular pulmonary artery patch repair, and right ventricle-pulmonary artery conduit placement. In the past few decades, surgery has proved successful, but most patients require repeat imaging throughout their lives. MR imaging is now frequently used for morphologic and functional evaluation after TOF repair. The most common late postoperative sequelae and residual lesions include right ventricular outflow tract aneurysm and dyskinesis, conduit failure, pulmonary regurgitation, tricuspid regurgitation, right ventricular failure, residual main and branch pulmonary artery stenosis, branch pulmonary artery aneurysm, left pulmonary artery kinking, and residual or recurrent ventricular septal defect. The imaging approach for the evaluation of patients with repaired TOF should be guided by the surgical procedure used and the complications that are expected. Knowledge of the most common postoperative problems and their cardiovascular MR imaging appearances is essential for good radiology practice in this clinical setting.
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http://dx.doi.org/10.1148/rg.334115084DOI Listing
February 2014

Quality assessment of cardiovascular magnetic resonance in the setting of the European CMR registry: description and validation of standardized criteria.

J Cardiovasc Magn Reson 2013 Jun 20;15:55. Epub 2013 Jun 20.

Department of Cardiology, Center of Cardiac Magnetic Resonance (CRMC), University Hospital Lausanne, Lausanne, Switzerland.

Background: Cardiovascular magnetic resonance (CMR) has become an important diagnostic imaging modality in cardiovascular medicine. However, insufficient image quality may compromise its diagnostic accuracy. We aimed to describe and validate standardized criteria to evaluate a) cine steady-state free precession (SSFP), b) late gadolinium enhancement (LGE), and c) stress first-pass perfusion images. These criteria will serve for quality assessment in the setting of the Euro-CMR registry.

Methods: Thirty-five qualitative criteria were defined (scores 0-3) with lower scores indicating better image quality. In addition, quantitative parameters were measured yielding 2 additional quality criteria, i.e. signal-to-noise ratio (SNR) of non-infarcted myocardium (as a measure of correct signal nulling of healthy myocardium) for LGE and % signal increase during contrast medium first-pass for perfusion images. These qualitative and quantitative criteria were assessed in a total of 90 patients (60 patients scanned at our own institution at 1.5T (n=30) and 3T (n=30) and in 30 patients randomly chosen from the Euro-CMR registry examined at 1.5T). Analyses were performed by 2 SCMR level-3 experts, 1 trained study nurse, and 1 trained medical student.

Results: The global quality score was 6.7±4.6 (n=90, mean of 4 observers, maximum possible score 64), range 6.4-6.9 (p=0.76 between observers). It ranged from 4.0-4.3 for 1.5T (p=0.96 between observers), from 5.9-6.9 for 3T (p=0.33 between observers), and from 8.6-10.3 for the Euro-CMR cases (p=0.40 between observers). The inter- (n=4) and intra-observer (n=2) agreement for the global quality score, i.e. the percentage of assignments to the same quality tertile ranged from 80% to 88% and from 90% to 98%, respectively. The agreement for the quantitative assessment for LGE images (scores 0-2 for SNR <2, 2-5, >5, respectively) ranged from 78-84% for the entire population, and 70-93% at 1.5T, 64-88% at 3T, and 72-90% for the Euro-CMR cases. The agreement for perfusion images (scores 0-2 for %SI increase >200%, 100%-200%,<100%, respectively) ranged from 81-91% for the entire population, and 76-100% at 1.5T, 67-96% at 3T, and 62-90% for the Euro-CMR registry cases. The intra-class correlation coefficient for the global quality score was 0.83.

Conclusions: The described criteria for the assessment of CMR image quality are robust with a good inter- and intra-observer agreement. Further research is needed to define the impact of image quality on the diagnostic and prognostic yield of CMR studies.
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http://dx.doi.org/10.1186/1532-429X-15-55DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707748PMC
June 2013

Combined delivery of bone marrow-derived mononuclear cells in chronic ischemic heart disease: rationale and study design.

Clin Cardiol 2013 Aug 29;36(8):435-41. Epub 2013 May 29.

Division of Cardiology, Ticino Cardiac Center Foundation, Lugano, Switzerland; Cell Therapy Unit, Ticino Cardiac Center, Lugano, Switzerland.

Background: Treatment with bone marrow-derived mononuclear cells (BM-MNC) may improve left ventricular (LV) function in patients with chronic ischemic heart disease (IHD). Delivery method of the cell product may be crucial for efficacy.

Hypothesis: We aimed to demonstrate that the combination of intramyocardial and intracoronary injection of BM-MNC is safe and improves LV function in patients with chronic IHD.

Methods: After a safety/feasibility phase of 10 patients, 54 patients will be randomly assigned 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 either exclusively intramyocardial injection or a combination of intramyocardial and intracoronary injection of autologous BM-MNC. Left ventricular function as well as scar size, transmural extension, and regional wall-motion score will be assessed by cardiac magnetic resonance imaging studies at baseline and after 6 months. The primary endpoint is the change in global LV ejection fraction by cardiac magnetic resonance from 6 months to baseline.

Results: The results, it is hoped, will have important clinical impact and provide essential information to improve the design of future regenerative-medicine protocols in cardiology.

Conclusions: As cell delivery may play an important role in chronic IHD, we aim to demonstrate feasibility and efficacy of a combined cell-delivery approach in patients with decreased LV function.
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http://dx.doi.org/10.1002/clc.22148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649397PMC
August 2013

Safety and tolerability of intensified, N-terminal pro brain natriuretic peptide-guided compared with standard medical therapy in elderly patients with congestive heart failure: results from TIME-CHF.

Eur J Heart Fail 2013 Aug 10;15(8):910-8. Epub 2013 May 10.

Maastricht University Medical Center, CARIM, Maastricht, The Netherlands.

Aims: NT-proBNP-guided therapy results in intensification of medical heart failure (HF) therapy and is suggested to improve outcome. However, it is feared that an intensified, NT-proBNP-guided therapy carries a risk of adverse effects. Therefore, the safety and tolerability of NT-proBNP-guided therapy in the Trial of Intensified vs standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) was assessed.

Methods And Results: A total of 495 chronic HF patients, aged ≥60, with an LVEF ≤45%, NYHA class ≥II, randomized to NT-proBNP-guided or symptom-guided therapy and ≥1 month follow-up were included in the present safety analysis. All adverse events (AEs) were recorded during the 18-month trial period. A total of 5212 AEs were noted, 433 of them serious. NT-proBNP-guided therapy led to a higher up-titration of HF medication and was well tolerated, with a dropout rate (12% vs. 11%, P = 1.0) and AE profile [number of AEs/patient-year 4.7 (2.8-9.4) vs. 5.4 (2.7-11.4), P = 0.69; number of severe AEs/patient-year 0.7 (0-2.7) vs. 1.3 (0-3.9), P = 0.21] similar to that of symptom-guided therapy, although most subjects in both treatment groups (96% vs. 95%, P = 0.55) experienced at least one AE. Age and number of co-morbidities were associated with AEs and interacted with the safety profile of NT-proBNP-guided therapy: positive effects were more frequent in younger and less co-morbid patients whereas potential negative effects-although small and related to non-severe AEs only-were only seen in the older and more co-morbid patients.

Conclusions: NT-proBNP-guided therapy is safe in elderly and highly co-morbid HF patients. Trial registration ISRCTN43596477.
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http://dx.doi.org/10.1093/eurjhf/hft079DOI Listing
August 2013

Role of real-time three dimensional transoesophageal echocardiography as guidance imaging modality during catheter based edge-to-edge mitral valve repair.

Heart 2013 Aug 16;99(16):1204-15. Epub 2013 Feb 16.

Division of Cardiology, Fondazione Cardiocentro Ticino, Via Tesserete 48, CH-6900 Lugano, Switzerland.

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http://dx.doi.org/10.1136/heartjnl-2012-302527DOI Listing
August 2013

Cognitive impairment in heart failure: results from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) randomized trial.

Eur J Heart Fail 2013 Jun 5;15(6):699-707. Epub 2013 Feb 5.

Department of Neurology, Maastricht University Medical Centre, Maastricht, The Netherlands.

Aims: Up to 50% of patients with heart failure (HF) may suffer from severe cognitive impairment (SCI), but longitudinal studies are sparse, and effects of changes in HF severity on cognitive function are unknown. Therefore, we assessed the prevalence of SCI in HF patients, its relationship with HF severity, its effects on morbidity and mortality, and the relationship between changes in HF severity and cognitive function.

Methods And Results: We included 611 patients from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) and assessed cognitive function [Hodkinson Abbreviated Mental Test (AMT)] in relation to severity of HF (NYHA class, NT-proBNP) at baseline and 18 months (n = 382) and effects on hospitalization-free survival and mortality. SCI (i.e. AMT score ≤ 7) was present in 9.2% of patients at baseline, but only 20% of them had a diagnosis of dementia. Prevalence of SCI remained stable during follow-up. SCI was present at baseline more often in NYHA IV patients compared with NYHA II [odds ratio 2.94; 95% confidence interval (CI) 1.15-7.51, P = 0.025], but it was not related to NT-proBNP levels. SCI was related to higher mortality (hazard ratio 1.53, 95% CI 1.02-2.30, P = 0.04), but not hospitalization-free survival. Changes in HF severity were not significantly related to changes in cognitive function.

Conclusion: SCI is a frequent, but often unrecognized finding in HF patients, but the influence of HF severity and its changes on cognitive function were less than hypothesized. Trial registration ISRCTN43596477.
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http://dx.doi.org/10.1093/eurjhf/hft020DOI Listing
June 2013

Relationship between the resting heart rate and the extent of coronary artery disease as assessed by myocardial perfusion SPECT.

Swiss Med Wkly 2012 13;142:w13660. Epub 2012 Aug 13.

Department of Cardiology, University Hospital Basel, Switzerland.

Aim: Sustained elevation of resting heart rate (RHR) is thought to promote the initiation and progression of coronary artery disease (CAD). The aim of this paper is to test the hypothesis whether elevated RHR correlates with the presence and the extent of CAD in patients evaluated for CAD.

Methods And Results: The association between RHR and CAD findings and myocardial perfusion SPECT (MPS) was tested in 1,465 patients. Patients with atrial fibrillation, pacemaker rhythm and treatment with negative chonotropic drugs were excluded. Standard scores for MPS evaluation were used. CAD findings of myocardial ischaemia or scar were present in 408 patients (28%). The prevalence of CAD finding at MPS was not higher among patients with RHR above the median value of 79 bpm compared to patients with lower RHR (28% vs 28%; p = 1.00). The extent of myocardial ischaemia and scar did not increase with higher quartiles of RHR. In contrast, the presence of other established cardiovascular risk factors such as diabetes, male gender, more advanced age and presence of CAD symptoms such as angina and dyspnoea were independent predictors of CAD findings (p <0.05 for all).

Conclusion: Elevated RHR is not associated with the presence and the extent of CAD in patients evaluated for suspected but previously unknown CAD, suggesting that the impact of a higher RHR on mortality may be linked with other factors than only CAD itself.
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http://dx.doi.org/10.4414/smw.2012.13660DOI Listing
January 2013

[Cardiac magnetic resonance in acute myocarditis: a new non-invasive diagnostic gold standard?].

Rev Med Suisse 2012 May;8(343):1177-83

Service de cardiologie, CHUV, Lausanne.

Acute myocarditis was until recently one of the most difficult diagnoses in cardiology. The spectrum of signs and symptoms is very wide, the usual non-invasive tests lack specificity and the myocardial biopsy is only performed in a minority of cases to confirm the diagnosis. Due to its unique ability to directly image myocardial necrosis, fibrosis and oedema, cardiac magnetic resonance (CMR) is now considered the primary tool for noninvasive assessment of patients with suspected myocarditis. CMR is also useful for monitoring disease activity under treatment. Myocarditis has been associated with the development of dilated cardiomyopathy; CMR could play a role in the follow-up of such cases to detect the progression toward a dilatative phenotype. Precise mapping of myocardial lesions with cardiac MRI is invaluable to guide myocardial biopsy and increase its diagnostic yield by improving sensitivity.
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May 2012

Cost evaluation of cardiovascular magnetic resonance versus coronary angiography for the diagnostic work-up of coronary artery disease: application of the European Cardiovascular Magnetic Resonance registry data to the German, United Kingdom, Swiss, and United States health care systems.

J Cardiovasc Magn Reson 2012 Jun 14;14:35. Epub 2012 Jun 14.

Institute of Health Economics and Management (IEMS), University of Lausanne, Lausanne, Switzerland.

Background: Cardiovascular magnetic resonance (CMR) has favorable characteristics for diagnostic evaluation and risk stratification of patients with known or suspected CAD. CMR utilization in CAD detection is growing fast. However, data on its cost-effectiveness are scarce. The goal of this study is to compare the costs of two strategies for detection of significant coronary artery stenoses in patients with suspected coronary artery disease (CAD): 1) Performing CMR first to assess myocardial ischemia and/or infarct scar before referring positive patients (defined as presence of ischemia and/or infarct scar to coronary angiography (CXA) versus 2) a hypothetical CXA performed in all patients as a single test to detect CAD.

Methods: A subgroup of the European CMR pilot registry was used including 2,717 consecutive patients who underwent stress-CMR. From these patients, 21% were positive for CAD (ischemia and/or infarct scar), 73% negative, and 6% uncertain and underwent additional testing. The diagnostic costs were evaluated using invoicing costs of each test performed. Costs analysis was performed from a health care payer perspective in German, United Kingdom, Swiss, and United States health care settings.

Results: In the public sectors of the German, United Kingdom, and Swiss health care systems, cost savings from the CMR-driven strategy were 50%, 25% and 23%, respectively, versus outpatient CXA. If CXA was carried out as an inpatient procedure, cost savings were 46%, 50% and 48%, respectively. In the United States context, cost savings were 51% when compared with inpatient CXA, but higher for CMR by 8% versus outpatient CXA.

Conclusion: This analysis suggests that from an economic perspective, the use of CMR should be encouraged as a management option for patients with suspected CAD.
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http://dx.doi.org/10.1186/1532-429X-14-35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461475PMC
June 2012

Incidence, clinical predictors, and prognostic impact of worsening renal function in elderly patients with chronic heart failure on intensive medical therapy.

Am Heart J 2012 Mar;163(3):407-14, 414.e1

Cardiology Division, Kantonsspital St Gallen, St Gallen, Switzerland.

Background: Incidence, predictors, and prognostic impact of worsening renal function (WRF) in elderly patients with chronic heart failure (HF) undergoing intensive contemporary medical therapy are unknown.

Methods And Results: In 566 patients (age 77 ± 8 years) included in the TIME-CHF, serum creatinine (sCr) was repeatedly measured up to 6 months. Worsening renal function was classified as increase in sCr by 0.2 to 0.3 (WRFI), 0.3 to 0.5 (WRFII), or ≥0.5 mg/dL (WRFIII) within the first 6 months. Outcome events were assessed for 18 months.

Results: The incidence of WRF I, II, and III was 12%, 19%, and 22%, respectively. Worsening renal function III was associated with increased mortality (hazard ratio 1.98 [95% CI 1.27-3.07, P = .002] vs no WRF), whereas WRF I/II was not. History of renal failure, spironolactone treatment, higher baseline dose, and higher maximal increase in loop diuretic dose were independently associated with the occurrence of WRF III, whereas angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, and β-blocker use and allocation to N-terminal pro-B-type natriuretic peptide-guided management were not. Worsening renal function III was an independent predictor of death, death or hospitalization, and death or HF hospitalization also after adjusting for baseline characteristics.

Conclusions: One fifth of elderly patients with chronic HF experienced WRF III on 6-month intensive HF treatment. These patients had higher mortality, whereas patients with smaller sCr rises did not. Occurrence of WRF III was associated with high doses of loop diuretics and spironolactone use but not with other treatments.
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http://dx.doi.org/10.1016/j.ahj.2011.12.003DOI Listing
March 2012

Collateral flow measurement by phase-contrast magnetic resonance imaging for the assessment of systemic venous baffle patency after atrial switch repair for transposition of the great arteries.

J Thorac Imaging 2012 May;27(3):175-8

Department of Radiology, University Hospital of California, San Francisco, CA, USA.

Purpose: We aimed to describe and compare azygos vein flow patterns of patients with obstructed and unobstructed systemic venous baffle after atrial switch repair for d-transposition of the great arteries (TGA). We hypothesized that phase-contrast magnetic resonance imaging would enable characterization of retrograde collateral flow across the azygos vein in cases of systemic venous baffle obstruction.

Materials And Methods: This is a retrospective, cross-sectional study. Twelve patients with atrial switch repair for TGA were examined. Azygos flow index was measured with phase-contrast magnetic resonance imaging; comparison was made between patients with documented systemic venous baffle obstruction (n=3) and a control group of patients without baffle obstruction (n=9).

Results: Patients with systemic venous baffle obstruction had a distinctive azygos flow pattern that was retrograde and an increased amount of azygos flow compared with patients without obstruction [median (range), -436 (-455/-399) vs. 103 (51/125) mL/min/m2; P=0.01].

Conclusions: Patients with systemic venous baffle obstruction have a characteristic collateral flow across the azygos vein. Azygos vein flow measurement may be used for the assessment of baffle patency in patients after atrial switch repair for TGA. However, diagnostic accuracy needs to be tested in a larger population.
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http://dx.doi.org/10.1097/RTI.0b013e31823fb9a0DOI Listing
May 2012

Usefulness of cardiovascular magnetic resonance imaging to predict the need for intervention in patients with coarctation of the aorta.

Am J Cardiol 2012 Mar 22;109(6):861-5. Epub 2011 Dec 22.

Department of Radiology, University of California, San Francisco, School of Medicine, San Francisco, California, USA.

Cardiovascular magnetic resonance (CMR) imaging can predict hemodynamically significant coarctation of the aorta (CoA) with a high degree of discrimination. However, the ability of CMR to predict important clinical outcomes in this patient population is unknown. Therefore, we sought to define the ability of CMR to predict the need for surgical or transcatheter intervention in patients with CoA. We retrospectively reviewed the data from 133 consecutive patients who had undergone CMR for the evaluation of known or suspected CoA. The characteristics of the CMR-derived variables predicting the need for surgical or transcatheter intervention for CoA within 1 year were determined through logistic regression analysis. Therapeutic aortic intervention was performed in 41 (31%) of the 133 patients during the study period. The indexed minimum aortic cross-sectional area was the strongest predictor of subsequent intervention (area under the receiver operating characteristic curve 0.975) followed by heart rate-corrected deceleration time in the descending aorta (area under the receiver operating characteristic curve 0.951), and the percentage of flow increase (area under the receiver operating characteristic curve 0.867). The combination of the indexed minimum aortic cross-sectional area and rate-corrected deceleration time in the descending aorta provided the best predictive model (area under the receiver operating characteristic curve 0.986). In conclusion, CMR findings can predict the need for subsequent intervention in CoA. These findings reinforce the "gate-keeper role" of CMR to cardiac catheterization by providing valuable diagnostic and powerful prognostic information and could guide additional treatment of patients with CoA with the final intent of reducing the number of diagnostic catheterizations in such patients.
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http://dx.doi.org/10.1016/j.amjcard.2011.10.048DOI Listing
March 2012

Frequency and predictors of hyperkalemia in patients ≥60 years of age with heart failure undergoing intense medical therapy.

Am J Cardiol 2012 Mar 5;109(5):693-8. Epub 2011 Dec 5.

Department of Cardiology, University Hospital Basel, Switzerland.

Hyperkalemia is a concern in heart failure (HF), especially in older patients with co-morbidities. Previous studies addressing this issue have focused mainly on younger patients. This study was aimed at determining the frequency and predictors of hyperkalemia in older patients with HF undergoing intense medical therapy. Frequency and predictors of hyperkalemia were defined in patients (n = 566) participating in the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure, in which patients ≥60 years of age were randomized to a standard versus an intensified N-terminal brain natriuretic peptide-guided HF therapy. During an 18-month follow-up 76 patients (13.4%) had hyperkalemia (≥5.5 mmol/L) and 28 (4.9%) had severe hyperkalemia (≥6.0 mmol/L). Higher baseline serum potassium (odds ratio [OR] 2.92 per mmol/L), baseline creatinine (OR 1.11 per 10 μmol/L), gout (OR 2.56), New York Heart Association (NYHA) class (compared to NYHA class II, IV OR 3.08), higher dosage of spironolactone at baseline (OR 1.20 per 12.5 mg/day), and higher dose changes of spironolactone (compared to no dose change: 12.5 mg, OR 1.45; 25 mg, OR 2.52; >25 mg, OR 3.24) were independent predictors for development of hyperkalemia (p <0.05 for all comparisons). In conclusion, hyperkalemia is common in patients ≥60 years of age with HF undergoing intense medical therapy. Risk is increased in patients treated with spironolactone, in addition to patient-specific risk factors such as chronic kidney disease, higher serum potassium, advanced NYHA class, and gout. Careful surveillance of serum potassium and cautious use of spironolactone in patients at risk may help to decrease the incidence of potentially hazardous complications caused by hyperkalemia.
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http://dx.doi.org/10.1016/j.amjcard.2011.10.027DOI Listing
March 2012

End-of-life preferences of elderly patients with chronic heart failure.

Eur Heart J 2012 Mar 8;33(6):752-9. Epub 2011 Nov 8.

Department of Cardiology, University Hospital Basel, Basel, Switzerland.

Aims: Elderly heart failure (HF) patients are assumed to prefer improved quality of life over longevity, but sufficient data are lacking. Therefore, we assessed the willingness to trade survival time for quality-of-life (QoL) and the preferences for resuscitation.

Methods And Results: At baseline and after 12 and 18 months, 622 HF patients aged ≥60 years (77 ± 8 years, 74% NYHA-class ≥III) participating in the Trial of Intensified vs. standard Medical therapy in Elderly patients with Congestive Heart Failure had prospective evaluation of end-of-life preferences by answering trade-off questions (willingness to accept a shorter life span in return for living without symptoms) and preferences for resuscitation if necessary. The time trade-off question was answered by 555 patients (89%), 74% of whom were not willing to trade survival time for improved QoL. This proportion increased over time (Month 12: 85%, Month 18: 87%, P < 0.001). In multivariable analysis, willingness to trade survival time increased with age, female sex, a reduced Duke Activity Status Index, Geriatric Depression Score, and history of gout, exercise intolerance, constipation and oedema, but even combining these variables did not result in reliable prediction. Of 603 (97%) patients expressing their resuscitation preference, 51% wished resuscitation, 39% did not, and 10% were undecided, with little changes over time. In 430 patients resuscitation orders were known; they differed from patients' preferences 32% of the time. End-of-life preferences were not correlated to 18-month outcome.

Conclusion: Elderly HF patients are willing to address their end-of-life preferences. The majority prefers longevity over QoL and half wished resuscitation if necessary. Prediction of individual preferences was inaccurate.
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http://dx.doi.org/10.1093/eurheartj/ehr404DOI Listing
March 2012

Prediction of hemodynamic severity of coarctation by magnetic resonance imaging.

Am J Cardiol 2011 Nov 20;108(9):1335-40. Epub 2011 Aug 20.

Department of Radiology, University Hospital of California, San Francisco, California, USA.

A published formula containing minimal aortic cross-sectional area and the flow deceleration pattern in the descending aorta obtained by cardiovascular magnetic resonance predicts significant coarctation of the aorta (CoA). However, the existing formula is complicated to use in clinical practice and has not been externally validated. Consequently, its clinical utility has been limited. The aim of this study was to derive a simple and clinically practical algorithm to predict severe CoA from data obtained by cardiovascular magnetic resonance. Seventy-nine consecutive patients who underwent cardiovascular magnetic resonance and cardiac catheterization for the evaluation of native or recurrent CoA at Children's Hospital Boston (n = 30) and the University of California, San Francisco (n = 49), were retrospectively reviewed. The published formula derived from data obtained at Children's Hospital Boston was first validated from data obtained at the University of California, San Francisco. Next, pooled data from the 2 institutions were analyzed, and a refined model was created using logistic regression methods. Finally, recursive partitioning was used to develop a clinically practical prediction tree to predict transcatheter systolic pressure gradient ≥ 20 mm Hg. Severe CoA was present in 48 patients (61%). Indexed minimal aortic cross-sectional area and heart rate-corrected flow deceleration time in the descending aorta were independent predictors of CoA gradient ≥ 20 mm Hg (p <0.01 for both). A prediction tree combining these variables reached a sensitivity and specificity of 90% and 76%, respectively. In conclusion, the presented prediction tree on the basis of cutoff values is easy to use and may help guide the management of patients investigated for CoA.
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http://dx.doi.org/10.1016/j.amjcard.2011.06.051DOI Listing
November 2011

Diagnostic value of the flow profile in the distal descending aorta by phase-contrast magnetic resonance for predicting severe coarctation of the aorta.

J Magn Reson Imaging 2011 Jun;33(6):1440-6

Department of Radiology, University Hospital of California, San Francisco, California 94143-0628, USA.

Purpose: To compare aortic flow profiles at the level of the proximal descending (PDAo) and distal descending aorta (DDAo) in patients investigated for coarctation of the aorta (CoA), and compare their respective diagnostic value for predicting severe CoA. Diastolic flow decay in the PDAo predicts severe CoA, but flow measurements at this level are limited by flow turbulence, aliasing, and stent-related artifacts.

Materials And Methods: We studied 49 patients evaluated for CoA with phase contrast magnetic resonance imaging (PC-MRI). Parameters of diastolic flow decay in the PDAo and DDAo were compared. Their respective diagnostic value was compared with the standard reference of transcatheter peak gradient ≥20 mmHg.

Results: Flow measurement in the PDAo required repeated acquisition with adjustment of encoding velocity or location of the imaging plane in 69% of patients; measurement in the DDAo was achieved in single acquisition in all cases. Parameters of diastolic flow decay in the PDAo and DDAo, including rate-corrected (RC) deceleration time and RC flow deceleration yielded a good correlation (r = 0.78; P < 0.01, and r = 0.92; P < 0.01), and a similar diagnostic value for predicting severe CoA. The highest diagnostic accuracy was achieved by RC deceleration time at DDAo (sensitivity 85%, specificity 85%).

Conclusion: Characterization of aortic flow profiles at the DDAo offers a quick and reliable noninvasive means of assessing hemodynamically significant CoA.
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http://dx.doi.org/10.1002/jmri.22566DOI Listing
June 2011

Potential of delayed gadolinium enhancement magnetic resonance imaging for quantification of reverse remodeling of the peri-infarct zone in patients with ischemic cardiomyopathy treated with chronic vasodilator therapy: initial experience.

J Thorac Imaging 2012 Mar;27(2):121-4

Department of Radiology and Biomedical Imaging, University of California San Francisco, USA.

Purpose: The peri-infarct zone represents the morphologic substrate for reentry ventricular tachycardia after myocardial infarction, and its extent is a strong predictor of major cardiac events. Although delayed gadolinium enhancement magnetic resonance imaging (DGE-MRI) was shown to allow for detailed characterization of myocardial infarction by quantifying infarct core zone and peri-infarct zone volume, potentials of DGE-MRI for measuring changes in peri-infarct zone volume are unknown. Therefore, we aimed to assess changes in volume of the peri-infarct zone among patients with ischemic cardiomyopathy treated with chronic vasodilator therapy.

Materials And Methods: Core and peri-infarct zone volumes as assessed with DGE-MRI were measured in 5 patients at baseline and after 6 months treatment with sustained-release dipyridamole.

Results: Core zone volume remained stable during follow-up [median (range), 19 mL (9 to 42) vs. 16 mL (11 to 46); P=0.785]. The ratio between the peri-infarct zone and the core zone volume decreased significantly at 6 months compared with baseline [median (range), 0.22 (0.19 to 0.42) vs. 0.18 (0.09 to 0.32); P=0.043], and a trend toward reduction in peri-infarct zone volume was found [median (range), 5 mL (2 to 8) vs. 3 mL (2 to 6); P=0.059]. The peri-infarct zone volume decreased in all but 1 patient over the follow-up.

Conclusions: This initial experience suggests that reverse remodeling of the peri-infarct zone with reduction in peri-infarct zone volume may take place in patients with ischemic cardiomyopathy. Quantification of this process may be feasible with DGE-MRI, but further studies are needed to confirm this hypothesis and to further clarify the role of DGE-MRI for the assessment of changes in peri-infarct zone volume in patients with ischemic cardiomyopathy.
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http://dx.doi.org/10.1097/RTI.0b013e3182125fb8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3155017PMC
March 2012