Vassilios S. Vassiliou

Association between mid-wall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction

Background: Current guidelines only recommend the use of an implantable cardioverter defibrillator in patients with dilated cardiomyopathy for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF) <35%. However, registries of out-of-hospital cardiac arrests demonstrate that 70% to 80% of such patients have an LVEF >35%. Patients with an LVEF >35% also have low competing risks of death from nonsudden causes. Therefore, those at high risk of SCD may gain longevity from successful implantable cardioverter defibrillator therapy. We investigated whether late gadolinium enhancement (LGE) cardiovascular magnetic resonance identified patients with dilated cardiomyopathy without severe LV systolic dysfunction at high risk of SCD. Methods: We prospectively investigated the association between midwall LGE and the prespecified primary composite outcome of SCD or aborted SCD among consecutive referrals with dilated cardiomyopathy and an LVEF ≥40% to our center between January 2000 and December 2011 who did not have a preexisting indication for implantable cardioverter defibrillator implantation. Results: Of 399 patients (145 women, median age 50 years, median LVEF 50%, 25.3% with LGE) followed for a median of 4.6 years, 18 of 101 (17.8%) patients with LGE reached the prespecified end point, compared with 7 of 298 (2.3%) without (hazard ratio [HR], 9.2; 95% confidence interval [CI], 3.9–21.8; P<0.0001). Nine patients (8.9%) with LGE compared with 6 (2.0%) without (HR, 4.9; 95% CI, 1.8–13.5; P=0.002) died suddenly, whereas 10 patients (9.9%) with LGE compared with 1 patient (0.3%) without (HR, 34.8; 95% CI, 4.6–266.6; P<0.001) had aborted SCD. After adjustment, LGE predicted the composite end point (HR, 9.3; 95% CI, 3.9–22.3; P<0.0001), SCD (HR, 4.8; 95% CI, 1.7–13.8; P=0.003), and aborted SCD (HR, 35.9; 95% CI, 4.8–271.4; P<0.001). Estimated HRs for the primary end point for patients with an LGE extent of 0% to 2.5%, 2.5% to 5%, and >5% compared with those without LGE were 10.6 (95% CI, 3.9–29.4), 4.9 (95% CI, 1.3–18.9), and 11.8 (95% CI, 4.3–32.3), respectively. Conclusions: Midwall LGE identifies a group of patients with dilated cardiomyopathy and an LVEF ≥40% at increased risk of SCD and low risk of nonsudden death who may benefit from implantable cardioverter defibrillator implantation. Clinical Trial Registration: URL: http://clinicaltrials.gov. Unique identifier: NCT00930735.

Renal denervation in heart failure with preserved ejection fraction (RDT-PEF): a randomized controlled trial.

Heart failure with preserved ejection fraction (HFpEF) is associated with increased sympathetic nervous system (SNS) tone. Attenuating the SNS with renal denervation (RDT) might be helpful and there are no data currently in humans with HFpEF.

Tuberculous constrictive pericarditis

Introduction: Constrictive pericarditis is characterized by constriction of the heart secondary to pericardial inflammation. Cardiovascular magnetic resonance (CMR) imaging is useful imaging modality for addressing the challenges of confirming this diagnosis. It can be used to exclude other causes of right heart failure, such as pulmonary hypertension or myocardial infarction, determine whether the pericardium is causing constriction and differentiate it from restrictive cardiomyopathy, which also causes impaired cardiac filling. Case Presentation: A 77-year-old man from a country with high incidence of tuberculosis presented with severe dyspnea. Echocardiography revealed a small left ventricle with normal systolic and mildly impaired diastolic function. Left heart catheterization revealed non-obstructive coronary disease, not felt contributory to the dyspnea. Anatomy imaging with cardiovascular magnetic resonance imaging (CMR) showed global, severely thickened pericardium. Short tau inversion recovery (STIR) sequences for detection of oedema/ inflammation showed increased signal intensity and free breathing sequences confirmed septal flattening on inspiration. Late gadolinium imaging confirmed enhancement in the pericardium, with all findings suggestive of pericardial inflammation and constriction. Conclusions: CMRwith STIRsequences, free breathing sequences and late gadolinium imaging can prove extremely useful for diagnosing constrictive pericarditis.

T1 at 1.5T and 3T compared with conventional T2*at 1.5T for cardiac siderosis

BackgroundMyocardial black blood (BB) T2* relaxometry at 1.5T provides robust, reproducible and calibrated non-invasive assessment of cardiac iron burden. In vitro data has shown that like T2*, novel native Modified Look-Locker Inversion recovery (MOLLI) T1 shortens with increasing tissue iron. The relative merits of T1 and T2* are largely unexplored. We compared the established 1.5T BB T2* technique against native T1 values at 1.5T and 3T in iron overload patients and in normal volunteers.MethodsA total of 73 subjects (42 male) were recruited, comprising 20 healthy volunteers (controls) and 53 patients (thalassemia major 22, sickle cell disease 9, hereditary hemochromatosis 9, other iron overload conditions 13). Single mid-ventricular short axis slices were acquired for BB T2* at 1.5T and MOLLI T1 quantification at 1.5T and 3T.ResultsIn healthy volunteers, median T1 was 1014xa0ms (full range 939–1059xa0ms) at 1.5T and modestly increased to 1165ms (full range 1056–1224xa0ms) at 3T. All patients with significant cardiac iron overload (1.5Txa0T2* values <20xa0ms) had T1 values <939xa0ms at 1.5T, and <1056xa0ms at 3T. Associations between T2* and T1 were found to be moderate with y =377u2009·u2009x0.282 at 1.5T (R2u2009=u20090.717), and y =406u2009·u2009x0.294 at 3T (R2u2009=u20090.715). Measures of reproducibility of T1 appeared superior to T2*.ConclusionsT1 mapping at 1.5T and at 3T can identify individuals with significant iron loading as defined by the current gold standard T2* at 1.5T. However, there is significant scatter between results which may reflect measurement error, but it is also possible that T1 interacts with T2*, or is differentially sensitive to aspects of iron chemistry or other biology. Hurdles to clinical implementation of T1 include the lack of calibration against human myocardial iron concentration, no demonstrated relation to cardiac outcomes, and variation in absolute T1 values between scanners, which makes inter-centre comparisons difficult. The relative merits of T1 at 3T versus T2* at 3T require further consideration.

The Tpeak – Tend interval as an electrocardiographic risk marker of arrhythmic and mortality outcomes: a systematic review and meta-analysis

BACKGROUNDnThe Tpeak - Tend interval (the interval from the peak to the end of the T wave), an electrocardiographic marker reflecting transmural dispersion of repolarization, has been used to predict ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death in different clinical settings.nnnOBJECTIVEnThis systematic review and meta-analysis evaluated the significance of the Tpeak - Tend interval in predicting arrhythmic and/or mortality end points.nnnMETHODSnPubMed, Embase, Cochrane Library, and CINAHL Plus databases were searched through November 30,xa02016.nnnRESULTSnOf the 854 studies identified initially, 33 observational studies involving 155,856 patients were included in our meta-analysis. Tpeak - Tend interval prolongation (mean cutoff value 103.3 ± 17.4 ms) was a significant predictor of the arrhythmic or mortality outcomes (odds ratio [OR] 1.14; 95% confidence interval [CI] 1.11-1.17; P < .001). When different end points were analyzed, the ORs were as follows: VT/VF, 1.10 (95% CI 1.06-1.13; P < .0001); sudden cardiac death, 1.27 (95% CI 1.17-1.39; P < .0001); cardiovascular death, 1.40 (95% CI 1.19-1.64; P < .0001); and all-cause mortality, 4.56 (95% CI 0.62-33.68; P < .0001). Subgroup analysis for each disease revealed that the risk of VT/VF or death was highest for Brugada syndrome (OR 5.68; 95% CI 1.57-20.53; P < .01), followed by hypertension (OR 1.52; 95% CI 1.26-1.85; P < .0001), heart failure (OR 1.07; 95% CI 1.04-1.11; P < .0001), and ischemic heart disease (OR 1.06; 95% CI 1.02-1.10; P = 0.001).nnnCONCLUSIONnThe Tpeak - Tend interval is a useful risk stratification tool in different diseases and in the general population.

Midwall Fibrosis and 5-Year Outcome in Moderate and Severe Aortic Stenosis

Aortic stenosis (AS) is characterized by progressive narrowing of the valve and the hypertrophic response of the left ventricle (LV) that ensues [(1)][1]. Although initially adaptive, the hypertrophic response ultimately decompensates and patients transition from hypertrophy to heart failure,

Towards accurate and precise T 1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions

Mapping of the longitudinal relaxation time (T1) and extracellular volume (ECV) offers a means of identifying pathological changes in myocardial tissue, including diffuse changes that may be invisible to existing T1-weighted methods. This technique has recently shown strong clinical utility for pathologies such as Anderson-Fabry disease and amyloidosis and has generated clinical interest as a possible means of detecting small changes in diffuse fibrosis; however, scatter in T1 and ECV estimates offers challenges for detecting these changes, and bias limits comparisons between sites and vendors. There are several technical and physiological pitfalls that influence the accuracy (bias) and precision (repeatability) of T1 and ECV mapping methods. The goal of this review is to describe the most significant of these, and detail current solutions, in order to aid scientists and clinicians to maximise the utility of T1 mapping in their clinical or research setting. A detailed summary of technical and physiological factors, issues relating to contrast agents, and specific disease-related issues is provided, along with some considerations on the future directions of the field.

Cardiovascular magnetic resonance: Diagnostic utility and specific considerations in the pediatric population

Cardiovascular magnetic resonance is a non-invasive imaging modality which is emerging as important tool for the investigation and management of pediatric cardiovascular disease. In this review we describe the key technical and practical differences between scanning children and adults, and highlight some important considerations that must be taken into account for this patient population. Using case examples commonly seen in clinical practice, we discuss the important clinical applications of cardiovascular magnetic resonance, and briefly highlight key future developments in this field.

Magnetic resonance imaging phantoms for quality-control of myocardial T1 and ECV mapping: specific formulation, long-term stability and variation with heart rate and temperature

BackgroundMagnetic resonance imaging (MRI) phantoms are routinely used for quality assurance in MRI centres; however their long term stability for verification of myocardial T1/ extracellular volume fraction (ECV) mapping has never been investigated.MethodsNickel-chloride agarose gel phantoms were formulated in a reproducible laboratory procedure to mimic blood and myocardial T1 and T2 values, native and late after Gadolinium administration as used in T1/ECV mapping. The phantoms were imaged weekly with an 11 heart beat MOLLI sequence for T1 and long TR spin-echo sequences for T2, in a carefully controlled reproducible manner for 12xa0months.ResultsThere were only small relative changes seen in all the native and post gadolinium T1 values (up to 9.0xa0% maximal relative change in T1 values) or phantom ECV (up to 8.3xa0% maximal relative change of ECV, up to 2.2xa0% maximal absolute change in ECV) during this period. All native and post gadolinium T2 values remained stable over time with <2xa0% change.Temperature sensitivity testing showed MOLLI T1 values in the long T1 phantoms increasing by 23.9xa0ms per degree increase and short T1 phantoms increasing by 0.3xa0ms per degree increase. There was a small absolute increase in ECV of 0.069xa0% (~0.22xa0% relative increase in ECV) per degree increase.Variation in heart rate testing showed a 0.13xa0% absolute increase in ECV (~0.45xa0% relative increase in ECV) per 10 heart rate increase.ConclusionsThese are the first phantoms reported in the literature modeling T1 and T2 values for blood and myocardium specifically for the T1mapping/ECV mapping application, with stability tested rigorously over a 12xa0month period. This work has significant implications for the utility of such phantoms in improving the accuracy of serial scans for myocardial tissue characterisation by T1 mapping methods and in multicentre work.

Apixaban versus warfarin in atrial fibrillation.

To the Editor: In the article by Granger et al. describing the results of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study (Sept. 15 issue),1 it was disappointing that patients with atrial fibrillation who were treated with warfarin had an international normalized ratio (INR) within the therapeutic range only 62% of the time. This percentage is particularly low considering that such a range can be achieved 76% of the time among patients receiving warfarin in Europe.2 Therefore, the ARISTOTLE study was effectively comparing apixaban therapy with poorly controlled warfarin therapy. In the recently published registry from Europe,2 the rate of major bleeding was 2.6%, and the rate of thromboembolism was 1.4% per year, lower than the rates of 3.1% and 1.6%, respectively, that were seen in patients taking warfarin in the ARISTOTLE study and similar to the rates of 2.1% and 1.3% in those receiving apixaban. Thus, it is imperative that the authors provide the average time in the therapeutic INR range that was achieved by patients who had a complication and by those who did not. Second, a subgroup analysis including only patients with INR control at least 76% of the time should be provided. Only then can we decide whether apixaban is truly superior to warfarin or whether it should be considered only in patients with suboptimal INR control while receiving warfarin.