Background— Low-flow low-gradient (LFLG) is sometimes observed in severe aortic stenosis (AS) despite normal ejection fraction, but its frequency and mechanisms are still debated. We aimed to describe the characteristics of patients with LFLG AS and assess the presence of longitudinal left ventricular dysfunction in these patients. Methods and Results— In a multicenter prospective study, 340 consecutive patients with severe AS and normal ejection fraction were studied. Longitudinal left ventricular function was assessed by 2D-strain and global afterload by valvulo-arterial impedance. Patients were classified according to flow and gradient: low flow was defined as a stroke volume index ≤35 mL/m 2 , low gradient as a mean gradient ≤40 mm Hg. Most patients (n=258, 75.9%) presented with high-gradient AS, and 82 patients (24.1%) with low-gradient AS. Among the latter, 52 (15.3%) presented with normal flow and low gradient and 30 (8.8%) with LFLG. As compared with normal flow and low gradient, patients with LFLG had more severe AS (aortic valve area=0.7±0.12 cm 2 versus 0.86±0.14 cm 2 ), higher valvulo-arterial impedance (5.5±1.1 versus 4±0.8 mm Hg/mL/m 2 ), and worse longitudinal left ventricular function (basal longitudinal strain=−11.6±3.4 versus −14.8±3%; P <0.001 for all). Conclusions— LFLG AS is observed in 9% of patients with severe AS and normal ejection fraction and is associated with high global afterload and reduced longitudinal systolic function. Patients with normal-flow low-gradient AS are more frequent and present with less severe AS, normal afterload, and less severe longitudinal dysfunction. Severe left ventricular longitudinal dysfunction is a new explanation to the concept of LFLG AS.
Heart failure- (HF) and arrhythmia-related complications are the main causes of morbidity and mortality in patients with nonischemic dilated cardiomyopathy (NIDCM). Cardiovascular magnetic resonance (CMR) imaging is a noninvasive tool for risk stratification based on fibrosis assessment. Diffuse interstitial fibrosis in NIDCM may be a limitation for fibrosis assessment through late gadolinium enhancement (LGE), which might be overcome through quantitative T1 and extracellular volume (ECV) assessment. T1 and ECV prognostic value for arrhythmia-related events remain poorly investigated. We asked whether T1 and ECV have a prognostic value in NIDCM patients. This prospective multicenter study analyzed 225 patients with NIDCM confirmed by CMR who were followed up for 2 years. CMR evaluation included LGE, native T1 mapping and ECV values. The primary endpoint was the occurrence of a major adverse cardiovascular event (MACE) which was divided in two groups: HF-related events and arrhythmia-related events. Optimal cutoffs for prediction of MACE occurrence were calculated for all CMR quantitative values. Fifty-eight patients (26%) developed a MACE during follow-up, 42 patients (19%) with HF-related events and 16 patients (7%) arrhythmia-related events. T1 Z-score (p = 0.008) and global ECV (p = 0.001) were associated with HF-related events occurrence, in addition to left ventricular ejection fraction (p < 0.001). ECV > 32.1% (optimal cutoff) remained the only CMR independent predictor of HF-related events occurrence (HR 2.15 [1.14–4.07], p = 0.018). In the arrhythmia-related events group, patients had increased native T1 Z-score and ECV values, with both T1 Z-score > 4.2 and ECV > 30.5% (optimal cutoffs) being independent predictors of arrhythmia-related events occurrence (respectively, HR 2.86 [1.06–7.68], p = 0.037 and HR 2.72 [1.01–7.36], p = 0.049). ECV was the sole independent predictive factor for both HF- and arrhythmia-related events in NIDCM patients. Native T1 was also an independent predictor in arrhythmia-related events occurrence. The addition of ECV and more importantly native T1 in the decision-making algorithm may improve arrhythmia risk stratification in NIDCM patients. Trial registration NCT02352129. Registered 2nd February 2015—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02352129
The explosion of novel anticancer therapies has meant emergence of cardiotoxicity signals including atrial fibrillation (AF). Reliable data concerning the liability of anticancer drugs in inducing AF are scarce. Using the World Health Organization individual case safety report database, VigiBase®, we aimed to determine the association between anticancer drugs and AF.A disproportionality analysis evaluating the multivariable-adjusted reporting odds ratios for AF with their 99.97% confidence intervals was performed for 176 U.S. Food and Drug Administration (FDA)- or European Medicines Agency (EMA)-labelled anticancer drugs in VigiBase®, followed by a descriptive analysis of AF cases for the anticancer drugs identified in VigiBase®. ClinicalTrial registration number: NCT03530215. A total of 11 757 AF cases associated with at least one anticancer drug were identified in VigiBase® of which 95.8% were deemed serious. Nineteen anticancer drugs were significantly associated with AF of which 14 (74%) are used in haematologic malignancies and 9 (45%) represented new AF associations not previously confirmed in literature including immunomodulating agents (lenalidomide, pomalidomide), several kinase inhibitors (nilotinib, ponatinib, midostaurin), antimetabolites (azacytidine, clofarabine), docetaxel (taxane), and obinutuzumab, an anti-CD20 monoclonal antibody.Although cancer malignancy itself may generate AF, we identified 19 anticancer drugs significantly associated with a significant increase in AF over-reporting. This pharmacovigilance study provides evidence that anticancer drugs themselves could represent independent risk factors for AF development. Dedicated prospective clinical trials are now required to confirm these 19 associations. This list of suspected anticancer drugs should be known by physicians when confronted to AF in cancer patients, particularly in case of haematologic malignancies.
Purpose: Levosimendan is a novel positive inotropic calcium sensitizer agent used in acute heart failure.Although its favorable effects on right ventricular dysfunction were suggested, they were not supported with objective evidence.In this prospective, randomized, double-blind study, the effect of levosimendan on the right ventricular systolic and diastolic function were evaluated by tissue Doppler comparing them with dobutamine in patients with ischemic heart failure.Methods: Patients having an acute heart failure attack with ischemic cardiomyopathy and LVEF<40% were included to the study.Patients were randomized to levosimendan (12-24 µg/kg loading, 0.1 µg/kg/min 24-hours IV infusion, n=30, mean age: 64±10, 63% male) and dobutamine groups (5-10 µg/kg/min 24-hours infusion, n=32, mean age: 66±8, 54% male).Before and 24 hours after treatment, E and S wave velocities from tricuspid lateral annulus by tissue Doppler and systolic pulmonary artery pressure (SPAP) were measured. Results:The values before and after treatment in both groups were shown in Table .There were no differences detected in E, S wave velocities, SPAP, age and gender between two groups before treatment (p>0.05).S and E wave velocities were increased in levosimendan group whereas they were unchanged in dobutamine group after the treatment.SPAP has shown significant reduction in both groups.However, these reduction is greater in levosimendan group (p=0.01).There was no significant relationship between S and E wave velocities and SPAP in both groups.Conclusions: Levosimendan improves right ventricular systolic and diastolic functions independent of its reduction of SPAP due to direct vasodilator effect on the pulmonary vascular bed.These results elucidate the favorable effects of levosimendan on right ventricular dysfunction.
Purpose: Idiopathic pulmonary arterial hypertension (IPAH) prognosis depends on the capability of the right ventricle (RV) to preserve its function in face of increased afterload.We hypothesize that, as for the left ventricle, right intra-ventricular (IVD) dyssynchrony may have a negative effect on the overloaded RV.The aim of the study was to assess right IVD by incorporating activation times of longitudinal deformation across all RV segments, representing the longitudinal deformation the major contribution to chamber contraction.Methods: Eighty patients with IPAH (52 female subjects), without right bundle branch block, were consecutively enrolled.All patients underwent WHO functional evaluation, 6-minutes walking test, right heart catheterization and a comprehensive echocardiographic examination within 24 hours from invasive procedure.RV longitudinal myocardial deformation was assessed by using 2D Speckle Tracking Echocardiography (2DSTE).We defined RV dyssynchrony, next called RV-SD4, as the standard deviation (SD) of the time-intervals between QRS onset and peak longitudinal systolic strain of mid and basal segments of the RV free wall and the inter-ventricular septum.Results: Patients with IPAH showed regional abnormalities of RV function in terms of time to peak of longitudinal systolic strain as expressed by RV-SD4.Multivariate regression analysis revealed that QRS duration, RV end-diastolic area and pulmonary vascular resistances (PVR) were independent predictors of RV-SD4 (r2 =0,36; p=,0.00001).Actuarial rates of patients who experienced clinical worsening (CW) were 25% at 6 months, 32% and 48% at 1 and 2 years respectively.Event-free survivors had better WHO functional class, 6-minutes walking distance, hemodynamic status, morphological and functional echocardiographic parameters.Multivariate analysis showed cardiac index (unit 0.5, HR 0.36, CI 95% 0.23-0.57),RV fractional area change (unit 5, HR 0.79, CI 95% 0.67-0,93) and RV-SD4 (unit 5, HR 1.06 CI 95% 1.00-1.13)as independent predictors of CW (x 2 =46.8, p=000001).The optimal ROC-derived RV-SD4 cut-off value as indicator of CW was ≥ 23 (Sensibility 92%, Specificity 67%).Conclusions: Our findings suggest that right intra-ventricular dyssynchrony can be accurately described by the 2DSTE derived measure RV-SD4.That index of RV dyssynchrony can help to distinguish non invasively those IPAH patients with a worse clinical and hemodynamic profile and could be considered among independent predictors of clinical worsening.
