Left atrial volume during stress is associated with increased risk of arrhythmias in patients with hypertrophic cardiomyopathy

Introduction: In patients affected by hypertrophic cardiomyopathy (HCM), left atrial volume index (LAVi) is associated with an increased risk of tachyarrhythmias and major clinical events. To date, the clinical meaning of LAVi measured during exercise (stress LAVi [sLAVi]) has not yet been investigated in HCM. This study sought to evaluate the correlation between LAVi/sLAVi and clinical outcome (risk of arrhythmias and heart failure [HF]) in patients with HCM. Methods and Results: We enrolled a total of 51 consecutive patients with HCM (39 men; mean age: 39.41 ± 17.9 years) who underwent standard and stress echocardiography, following a common protocol. During follow-up (median follow-up was 1.82 years), the following composite endpoints were collected: ARRHYT endpoint (atrial fibrillation, paroxysmal supraventricular tachycardia, nonsustained ventricular tachycardia (VT), sustained VT, ventricular fibrillation, syncope of likely cardiogenic nature, and sudden cardiac death) and HF endpoint (worsening of functional class and left ventricular ejection fraction, hospitalization, and death for end-stage HF). Eight patients were lost at follow-up. ARRHYT endpoint occurred in 13 (30.2%) patients (8, 18.6%, supraventricular and 10, 23.2%, ventricular arrhythmias), whereas HF endpoint occurred in 5 (11.6%) patients. sLAVi (mean value of 31.16 ± 10.15 mL/m2) performed better than rLAVi as a predictor of ARRHYT endpoint (Akaike Information Criterion: 48.37 vs. 50.37, if dichotomized according to the median values). A sLAVi value of 30 mL/m2 showed a predictive accuracy of 72.1% (C-statistics of 0.7346), with a high negative predictive value (87.5%). Conclusion: These findings encourage future studies on sLAVi, as a potential predictor of arrhythmias and adverse outcome in patients with HCM

P4408Quadruple imaging stress echocardiography as the new standard

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Stress echo 2020: The international stress echo study in ischemic and non-ischemic heart disease

Abstract Background Stress echocardiography (SE) has an established role in evidence-based guidelines, but recently its breadth and variety of applications have extended well beyond coronary artery disease (CAD). We lack a prospective research study of SE applications, in and beyond CAD, also considering a variety of signs in addition to regional wall motion abnormalities. Methods In a prospective, multicenter, international, observational study design, > 100 certified high-volume SE labs (initially from Italy, Brazil, Hungary, and Serbia) will be networked with an organized system of clinical, laboratory and imaging data collection at the time of physical or pharmacological SE, with structured follow-up information. The study is endorsed by the Italian Society of Cardiovascular Echography and organized in 10 subprojects focusing on: contractile reserve for prediction of cardiac resynchronization or medical therapy response; stress B-lines in heart failure; hypertrophic cardiomyopathy; heart failure with preserved ejection fraction; mitral regurgitation after either transcatheter or surgical aortic valve replacement; outdoor SE in extreme physiology; right ventricular contractile reserve in repaired Tetralogy of Fallot; suspected or initial pulmonary arterial hypertension; coronary flow velocity, left ventricular elastance reserve and B-lines in known or suspected CAD; identification of subclinical familial ..

Quasiprojectile breakup and isospin equilibration at Fermi energies: an indication of longer projectile-target contact times?

An investigation of the quasiprojectile breakup channel in semiperipheral and peripheral collisions of $^{58,64}$Ni+$^{58,64}$Ni at 32 and 52 MeV/nucleon is presented. Data have been acquired in the first experimental campaign of the INDRA-FAZIA apparatus in GANIL. The effect of isospin diffusion between projectile and target in the two asymmetric reactions has been highlighted by means of the isospin transport ratio technique, exploiting the neutron-to-proton ratio of the quasiprojectile reconstructed from the two breakup fragments. We found evidence that, for the same reaction centrality, a higher degree of relaxation of the initial isospin imbalance is achieved in the breakup channel with respect to the more populated binary output, possibly indicating the indirect selection of specific dynamical features. We have proposed an interpretation based on different average projectile-target contact times related to the two exit channels under investigation, with a longer interaction for the breakup channel. The time information has been extracted from AMD simulations of the studied systems coupled to GEMINI++: the model calculations support the hypothesis hereby presented

Usefulness of NT-pro BNP monitoring to identify echocardiographic responders following cardiac resynchronization therapy

<p>Abstract</p> <p>Background</p> <p>Cardiac resynchronization therapy (CRT) improves left ventricular (LV) volumes, mitral regurgitation (MR) severity and symptoms of patients with heart failure (HF). However, ≥ 30% of patients have no significant clinical or echocardiographic improvement following CRT. Reverse remodeling after CRT correlates with improved clinical outcomes. We hypothesized that in NT-pro BNP monitoring is accurate to identify responders following CRT.</p> <p>Methods</p> <p>42 consecutive patients (mean age 66 ± 12 years, male 68%) with HF undergoing CRT were prospectively enrolled. Responders at follow-up were defined by echocardiography (decrease in LV end systolic volume ≥ 15%). Echocardiography and NT-pro BNP measurement were performed at baseline and repeated 3 to 6 month after CRT.</p> <p>Results</p> <p>There was no significant difference between responders (n = 29, 69%) and non-responders (n = 13, 31%) regarding baseline NT-pro BNP level. Responders had significantly higher decrease in NT-pro BNP levels during follow-up than non-responders (absolute: -1428 ± 1333 pg.ml^-1vs. -61 ± 959 pg.ml^-1, p = 0.002; relative: -45 ± 28% vs. 2 ± 28%, p < 0.0001). A decrease of ≥ 15% in NT-pro BNP 3–6 months after CRT identifies echocardiographic responders with a sensitivity of 90% and a specificity of 77%.</p> <p>Conclusion</p> <p>NT-pro BNP monitoring can accurately identify echocardiographic responders after CRT.</p

Reverse left ventricular remodeling is more likely in non ischemic cardiomyopathy patients upgraded to biventricular stimulation after chronic right ventricular pacing

<p>Abstract</p> <p>Background</p> <p>Chronic right ventricular (RV) apical pacing may lead to left ventricular (LV) dyssynchrony and LV dysfunction. In heart failure due to RV pacing, upgrading to biventricular stimulation (CRT) can improve NYHA Class and LV function. A proportion of patients do not respond to upgrading. Aim was to assess whether etiology of LV dysfunction accounts for responses to CRT in RV-paced patients.</p> <p>Methods</p> <p>Sixty-two patients treated by CRT, under RV pacing from 50.2 ± 5.4 months, were studied. Cause of LV dysfunction was non-ischemic (NIC) in 28 and ischemic cardiomyopathy (IC) in 34 patients. Clinical and conventional echocardiographic parameters were available within 1 month before RV pacing, within 1 month before CRT and at 12 ± 2 months of follow-up (FU).</p> <p>Results</p> <p>Decreased LVEF (from 37.0 ± 8.8 to 25.6 ± 6.1%, p <0.001), increased LV end-systolic dimensions (LVESD) (from 48.1 ± 8.6 to 55.2 ± 7.9 mm, p <0.001) and worsened NYHA Class (from 1.9 ± 1.1 to 3.2 ± .6, p < 0.005) were found before CRT, compared to pre RV-pacing. After CRT, 44/62 patients showed a ≥ 1 NYHA Class improvement; >10% decrease in LVESD was observed in 24 patients: 5 with IC, 19 with NIC (p < .0.001). The association between cause of LV dysfunction with >10% decrease in LVESD remained highly significant (p < 0.001) adjusting for pre-CRT QRS duration, NYHA Class, LVEF, LVESD, treatment or RV pacing duration.</p> <p>Conclusions</p> <p>CRT improves functional class even after long-lasting pacing. Reverse remodeling is evident in a small population, more likely with NIC.</p

Duplication of 7q34 is specific to juvenile pilocytic astrocytomas and a hallmark of cerebellar and optic pathway tumours

BACKGROUND: Juvenile pilocytic astrocytomas (JPA), a subgroup of low-grade astrocytomas (LGA), are common, heterogeneous and poorly understood subset of brain tumours in children. Chromosomal 7q34 duplication leading to fusion genes formed between KIAA1549 and BRAF and subsequent constitutive activation of BRAF was recently identified in a proportion of LGA, and may be involved in their pathogenesis. Our aim was to investigate additional chromosomal unbalances in LGA and whether incidence of 7q34 duplication is associated with tumour type or location. METHODS AND RESULTS: Using Illumina-Human-Hap300-Duo and 610-Quad high-resolution-SNP-based arrays and quantitative PCR on genes of interest, we investigated 84 paediatric LGA. We demonstrate that 7q34 duplication is specific to sporadic JPA (35 of 53-66%) and does not occur in other LGA subtypes (0 of 27) or NFI-associated-JPA (0 of 4). We also establish that it is site specific as it occurs in the majority of cerebellar JPA (24 of 30-80%) followed by brainstem, hypothalamic/optic pathway JPA (10 of 16-62.5%) and is rare in hemispheric JPA (1 of 7-14%). The MAP-kinase pathway, assessed through ERK phosphorylation, was active in all tumours regardless of 7q34 duplication. Gain of function studies performed on hTERT-immortalised astrocytes show that overexpression of wild-type BRAF does not increase cell proliferation or baseline MAPK signalling even if it sensitises cells to EGFR stimulation. CONCLUSIONS AND INTERPRETATION: Our results suggest that variants of JPA might arise from a unique site-restricted progenitor cell where 7q34 duplication, a hallmark of this tumour-type in association to MAPK-kinase pathway activation, potentially plays a site-specific role in their pathogenesis. Importantly, gain of function abnormalities in components of MAP-Kinase signalling are potentially present in all JPA making this tumour amenable to therapeutic targeting of this pathway. British Journal of Cancer (2009) 101, 722-733. doi: 10.1038/sj.bjc.6605179 www.bjcancer.com Published online 14 July 2009 (C) 2009 Cancer Research U