LV Mass Assessed by Echocardiography and CMR, Cardiovascular Outcomes, and Medical Practice

The authors investigated 3 important areas related to the clinical use of left ventricular mass (LVM): accuracy of assessments by echocardiography and cardiac magnetic resonance (CMR), the ability to predict cardiovascular outcomes, and the comparative value of different indexing methods. The recommended formula for echocardiographic estimation of LVM uses linear measurements and is based on the assumption of the left ventricle (LV) as a prolate ellipsoid of revolution. CMR permits a modeling of the LV free of cardiac geometric assumptions or acoustic window dependency, showing better accuracy and reproducibility. However, echocardiography has lower cost, easier availability, and better tolerability. From the MEDLINE database, 26 longitudinal echocardiographic studies and 5 CMR studies investigating LVM or LV hypertrophy as predictors of death or major cardiovascular outcomes were identified. LVM and LV hypertrophy were reliable cardiovascular risk predictors using both modalities. However, no study directly compared the methods for the ability to predict events, agreement in hypertrophy classification, or performance in cardiovascular risk reclassification. Indexing LVM to body surface area was the earliest normalization process used, but it seems to underestimate the prevalence of hypertrophy in obese and overweight subjects. Dividing LVM by height to the allometric power of 1.7 or 2.7 is the most promising normalization method in terms of practicality and usefulness from a clinical and scientific standpoint for scaling myocardial mass to body size. The measurement of LVM, calculation of LVM index, and classification for LV hypertrophy should be standardized by scientific societies across measurement techniques and adopted by clinicians in risk stratification and therapeutic decision making

Peroxynitrite Inhibits Glutamate Transporter Subtypes

The reuptake of glutamate in neurons and astrocytes terminates excitatory signals and prevents the persistence of excitotoxic levels of glutamate in the synaptic cleft. This process is inhibited by oxygen radicals and hydrogen peroxide (H2O2). Here we show that another biological oxidant, peroxynitrite (ONOO-), formed by combination of superoxide (O2-) and nitric oxide (NO), potently inhibits glutamate uptake by purified or recombinant high affinity glutamate transporters reconstituted in liposomes. ONOO- reduces selectively the Vmax of transport; its action is fast (reachingor = 90% within 20 s), dose-dependent (50% inhibition at 50 microM), persistent upon ONOO- (or by product) removal, and insensitive to the presence of the lipid antioxidant vitamin E in the liposomal membranes. Therefore, it likely depends on direct interaction of ONOO- with the glutamate transporters. Three distinct recombinant glutamate transporters from the rat brain, GLT1, GLAST, and EAAC1, exhibit identical sensitivity to ONOO . H2O2 also inhibits reconstituted transport, and its action matches that of ONOO- on all respects; however, this is observed only with 5-10 mM H202 and after prolonged exposure (10 min) in highly oxygenated buffer. NO, released from NO donors (up to 10 mM), does not modify reconstituted glutamate uptake, although in parallel conditions it promotes cGMP formation in synaptosomal cytosolic fraction. Overall, our results suggest that the glutamate transporters contain conserved sites in their structures conferring vulnerability to ONOO- and other oxidants

Cause-Specific Mortality in Patients During Long-Term Follow-Up After Atrial Switch for Transposition of the Great Arteries

Background Little is known about the cause of death (CoD) in patients with transposition of the great arteries palliated with a Mustard or Senning procedure. The aim was to describe the CoD for patients with the Mustard and Senning procedure during short- (20 years) follow-up after the operation. Methods and Results This is a retrospective, descriptive multicenter cohort study including all Nordic patients (Denmark, Finland, Norway, and Sweden) who underwent a Mustard or Senning procedure between 1967 and 2003. Patients who died within 30 days after the index operation were excluded. Among 968 patients with Mustard/Senning palliated transposition of the great arteries, 814 patients were eligible for the study, with a mean follow-up of 33.6 years. The estimated risk of all-cause mortality reached 36.0% after 43 years of follow-up, and the risk of death was highest among male patients as compared with female patients (P=0.004). The most common CoD was sudden cardiac death (SCD), followed by heart failure/heart transplantation accounting for 29% and 27%, respectively. During short-, mid-, and long-term follow-up, there was a change in CoD with SCD accounting for 23.7%, 46.6%, and 19.0% (P=0.002) and heart failure/heart transplantation 18.6%, 22.4%, and 46.6% (P=0.0005), respectively. Conclusions Among patients corrected with Mustard or Senning transposition of the great arteries, the most common CoD is SCD followed by heart failure/heart transplantation. The CoD changes as the patients age, with SCD as the most common cause in adolescence and heart failure as the dominant cause in adulthood. Furthermore, the risk of all-cause mortality, SCD, and death attributable to heart failure or heart transplantation was increased in men >10 years after the Mustard/Senning operation.Peer reviewe

Factors determining the magnitude of the pre-ejection leftward septal motion in left bundle branch block

AIMS: An abnormal large leftward septal motion prior to ejection is frequently observed in left bundle branch block (LBBB) patients. This motion has been proposed as a predictor of response to cardiac resynchronization therapy (CRT). Our goal was to investigate factors that influence its magnitude. METHODS AND RESULTS: Left (LVP) and right ventricular (RVP) pressures and left ventricular (LV) volume were measured in eight canines. After induction of LBBB, LVP and, hence, the transmural septal pressure (P(LV–RV) = LVP–RVP) increased more slowly (P < 0.01) during the phase when septum moved leftwards. A biventricular finite-element LBBB simulation model confirmed that the magnitude of septal leftward motion depended on reduced rise of P(LV–RV). The model showed that leftward septal motion was decreased with shorter activation delay, reduced global or right ventricular (RV) contractility, septal infarction, or when the septum was already displaced into the LV at end diastole by RV volume overload. Both experiments and simulations showed that pre-ejection septal hypercontraction occurs, in part, because the septum performs more of the work pushing blood towards the mitral valve leaflets to close them as the normal lateral wall contribution to this push is lost. CONCLUSIONS: Left bundle branch block lowers afterload against pre-ejection septal contraction, expressed as slowed rise of P(LV–RV), which is a main cause and determinant of the magnitude of leftward septal motion. The motion may be small or absent due to septal infarct, impaired global or RV contractility or RV volume overload, which should be kept in mind if this motion is to be used in evaluation of CRT response

Comparison of Electrocardiography Markers and Speckle Tracking Echocardiography for Assessment of Left Ventricular Myocardial Scar Burden in Patients With Previous Myocardial Infarction

Myocardial scar burden is an important prognostic factor after myocardial infarction. This cohort study compared assessment of left ventricle scar burden between pathological Q waves on electrocardiography (ECG), Selvester multiparametric ECG scoring system for scar burden, and global longitudinal strain (GLS) by speckle-tracking echocardiography 6 months after myocardial infarction. The scar burden was defined by late gadolinium enhancement cardiac magnetic resonance as fraction of total left ventricle tissue. ECG measures were presence of pathologic Q waves and Selvester scores. GLS was the average of peak strain from 16 left ventricle segments. In 34 patients aged 58 ± 10 years (mean ± SD), the scar burden was 19% (9, 26) (median [quartiles]) and 79% had scar burden >5%. Patients with scar burden >5% more frequently had pathologic Q waves (63% vs 14%) and had worse Selvester scores (5 [3, 7] vs 0 [0, 1]) and worse GLS (−16.6 ± 2.4% vs −19.9 ± 1.1%). Pathologic Q waves, Selvester scores, ejection fraction, and GLS related to scar burden in univariable analyses. Sensitivity and specificity for detecting scar burden >5% was 63% and 86% (pathologic Q waves), 89% and 86% (Selvester score), 81% and 86% (ejection fraction), 89% and 86% (GLS), and 96% and 71% (combination of Q waves, Selvester score, and GLS). In conclusion, Selvester score and GLS related to scars 6 months after myocardial infarction, and pathologic Q waves were only weakly associated with scar and GLS was associated with scar independently of ECG markers