Trimethylplatinum(IV) complexes of dithiocarbamato ligands: an experimental NMR study on the barrier to C-N bond rotation.

The trimethylplatinum(IV) complexes of a number of dithiocarbamato ligands have been prepared. The complexes are dimeric in the solid-state and in solution, with the ligands acting in both a bridging and chelating fashion. Restricted rotation about the ligand C-N bonds in solution leads to the formation of four rotomers. The kinetics of the restricted rotation were measured by a variety of dynamic NMR techniques in the slow and intermediate exchange regimes. Two distinct processes are observed, namely the independent rotation about each C-N bond and correlated rotation about both C-N bonds. The free energies of activation, which are strongly dependent on the nature of the ligand substituents, are in the range 65 – 88 kJ mol-1 at 298 K. The origins of the barrier to rotation and the effects of the N substituents are discussed. The X-ray structures of fac-[PtMe3(Me2NCS2)]2 (2) and fac-[PtMe3(Ph(H)NCS2)]2 , (6) are reported

Speckle-Tracking Echocardiography for Predicting Outcome in Chronic Aortic Regurgitation During Conservative Management and After Surgery

ObjectivesThe aim of this study was to test myocardial deformation imaging using speckle-tracking echocardiography for predicting outcomes in chronic aortic regurgitation.BackgroundIn chronic aortic regurgitation, left ventricular (LV) dysfunction must be detected early to allow timely surgery. Speckle-tracking echocardiography has been proposed for this purpose, but the clinical value of this method in aortic regurgitation has not been established.MethodsA longitudinal study was performed in 64 patients with moderate to severe aortic regurgitation. Thirty-five patients were managed conservatively with frequent clinical visits and sequential echocardiography and followed for an average of 19 ± 8 months, while 29 patients underwent surgery for the valve lesion and were followed for 6 months post-operatively. Baseline LV function by speckle-tracking and conventional echocardiography was compared with impaired outcome after surgery (defined as persisting symptoms or persisting LV dilation [LV end-diastolic volume index ≥87 ml/m2] or dysfunction [LV ejection fraction <50%]) and with disease progression during conservative management (defined as development of symptoms, increase in LV volume >15%, or decrease in LV ejection fraction >10%).ResultsReduced myocardial systolic strain, systolic strain rate, and early diastolic strain rate by speckle-tracking echocardiography was associated with disease progression during conservative management (−16.3% vs. −19.0%, p = 0.02; −1.04 vs. −1.19 s−1, p = 0.02; and 1.20 vs. 1.60 s−1, p = 0.002, respectively) and with impaired outcome after surgery (−11.5% vs. −15.6%, p = 0.01; −0.88 vs. −1.01 s−1, p = 0.04; and 0.98 vs. 1.33 s−1, p = 0.01, respectively). Conventional parameters of LV function and size (LV ejection fraction and LV end-diastolic volume index) were associated with outcome after surgery (p = 0.04 and p = 0.01, respectively) but not with outcome during conservative management (p = 0.57 and p = 0.39, respectively).ConclusionsSpeckle-tracking echocardiography is useful for the early detection of LV systolic and diastolic dysfunction in chronic aortic regurgitation

Prognostic implications of left ventricular global longitudinal strain in heart failure patients with narrow QRS complex treated with cardiac resynchronization therapy: a subanalysis of the randomized EchoCRT trial

Aim: Left ventricular (LV) global longitudinal strain (GLS) reflects LV systolic function and correlates inversely with the extent of LV myocardial scar and fibrosis. The present subanalysis of the Echocardiography Guided CRT trial investigated the prognostic value of LV GLS in patients with narrow QRS complex. Methods and results: Left ventricular (LV) global longitudinal strain (GLS) was measured on the apical 2-, 4- and 3-chamber views using speckle tracking analysis. Measurement of baseline LV GLS was feasible in 755 patients (374 with cardiac resynchronization therapy (CRT)-ON and 381 with CRT-OFF). The median value of LV GLS in the overall population was 7.9%, interquartile range 6.2–10.1%. After a mean follow-up period of 19.4 months, 95 patients in the CRT-OFF group and 111 in the CRT-ON group reached the combined primary endpoint of all-cause mortality and heart failure hospitalization. Each 1% absolute unit decrease in LV GLS was independently associated with 11% increase in the risk to reach the primary endpoint (Hazard ratio 1.11; 95% confidence interval 95% 1.04–1.17, P &lt; 0.001), after adjusting for ischaemic cardiomyopathy and randomization treatment among other clinically relevant variables. When categorizing patients according to quartiles of LV GLS, the primary endpoint occurred more frequently in patients in the lowest quartile (&lt;6.2%) treated with CRT-ON vs. CRT-OFF (45.6% vs. 28.7%, P = 0.009) whereas, no differences were observed in patients with LV GLS ≥6.2% treated with CRT-OFF vs. CRT-ON (23.7% vs. 24.5%, respectively; P  = 0.62). Conclusion: Low LV GLS is associated with poor outcome in heart failure patients with QRS width &lt;130 ms, independent of randomization to CRT or not. Importantly, in the group of patients with the lowest LV GLS quartile, CRT may have a detrimental effect on clinical outcomes

Prevalence and inter-relationship of different Doppler measures of dyssynchrony in patients with heart failure and prolonged QRS: a report from CARE-HF

Background: Cardiac resynchronisation therapy (CRT) improves mortality and morbidity in heart failure patients with wide QRS. Observational studies suggest that patients having more left ventricular dyssynchrony pre-implantation obtain greater benefit on ventricular function and symptoms with CRT.Aim: To provide an analysis of the prevalence and type of dyssynchrony in patients included in the CARE-HF trial.Methods: 100 patients 67 (58 to 71) years were examined with echocardiography including tissue doppler imaging before receiving a CRT-pacemaker. Atrio-ventricular dyssynchrony (LVFT/RR) was defined as left ventricular filling time <40% of the RR-interval. Inter-ventricular mechanical delay (IVMD) was measured as the difference in onset of Doppler-flow in the pulmonary and aortic outflow tracts >40 ms. Intraventricular (regional) dyssynchrony in a 16-segment model was expressed either as a delayed longitudinal contraction (DLC) during the postsystolic phase or by tissue synchronisation imaging (TSI) with a predefined time-difference in systolic maximal velocities >85 ms.Results: LVFT/RR was present in 34% and IVMD in 60% of patients while intra-ventricular dyssynchrony was present in 85% (DLC) and 86% (TSI) with a high agreement between the measures (Kappascore 0.86-1.00), indicating the methods being interchangeable. Patients with cardiomyopathy (53%) were more likely to have LVFT/RR <40% (45% vs. 21% (p= 0.02)) and more segments affected by intra-ventricular dyssynchrony 4(3, 5) vs. 3(1, 4), p = 0.002, compared to patients with ischemic heart disease.Conclusion: The prevalence of intra-ventricular dyssynchrony is high in patients with heart failure, wide QRS and depressed systolic function. Most important, TSI appears to be a fast and reliable method to identify patients with intra-ventricular dyssynchrony likely to benefit from CRT

Thromboembolism and bleeding in patients with atrial fibrillation and liver disease - a nationwide register-based cohort study:Thromboembolism and bleeding in liver disease

BackgroundBalancing the risk of thromboembolism and bleeding in patients with liver disease and atrial fibrillation/flutter is particularly challenging.PurposeTo examine the risks of thromboembolism and bleeding with use/non-use of oral anticoagulation (including vitamin K-antagonists and direct oral anticoagulants) in patients with liver disease and AF.MethodsDanish nationwide register-based cohort study of anticoagulant naive individuals with liver disease, incident atrial fibrillation/flutter, and a CHA2DS2-VASc-score≥1 (men) or ≥2 (women), alive 30 days after atrial fibrillation/flutter diagnosis. Thromboembolism was a composite of ischaemic stroke, transient ischaemic attack, or venous thromboembolism. Bleeding was a composite of gastrointestinal, intracerebral, or urogenital bleeding requiring hospitalisation, or epistaxis requiring emergency department visit or hospital admission. Cause-specific Cox-regression was used to estimate absolute risks and average risk ratios standardised to covariate distributions. Because of significant interactions with anticoagulants, results for thromboembolism were stratified for CHA2DS2-VASc-score, and results for bleeding were stratified for cirrhotic/non-cirrhotic liver disease.ResultsFour hundred and nine of 1,238 patients with liver disease and new atrial fibrillation/flutter initiated anticoagulants. Amongst patients with a CHA2DS2-VASc-score of 1-2 (2-3 for women), five-year thromboembolism incidence rates were low and similar in the anticoagulant (6.5%) versus no anticoagulant (5.5%) groups (average risk ratio 1.19 [95%CI, 0.22-2.16]). In patients with a CHA2DS2-VASc-score>2 (>3 for women), incidence rates were 16% versus 24% (average risk ratio 0.66 [95%CI, 0.45-0.87]). Bleeding risks appeared higher amongst patients with cirrhotic versus non-cirrhotic disease but were not significantly affected by anticoagulant status.ConclusionOral anticoagulant initiation in patients with liver disease, incident new atrial fibrillation/flutter, and a high CHA2DS2-VASc-score was associated with a reduced thromboembolism risk. Bleeding risk was not increased with anticoagulation, irrespective of the type of liver disease

Prognostic value of myocardial fibrosis in severe aortic stenosis:Study protocol for a prospective observational multi-center study (FIB-AS)

BACKGROUND: Adverse cardiac remodeling with a myocardial fibrosis as a key pathophysiologic component may be associated to worse survival in aortic stenosis (AS) patients. Therefore, with the application of advanced cardiac imaging we aim to investigate left ventricular myocardial fibrosis in severe AS patients undergoing aortic valve replacement (AVR) and determine its impact with post-intervention clinical outcomes. METHODS: In a prospective, observational, cohort study patients with severe AS scheduled either for surgical or transcatheter AVR will be recruited from two tertiary heart centers in Denmark and Lithuania. All patients will receive standard of care in accordance with the current guidelines and will undergo additional imaging testing before and after AVR: echocardiography with deformation analysis and cardiovascular magnetic resonance (CMR) with T1 parametric mapping. Those undergoing surgical AVR will also have a myocardial biopsy sampled at the time of a surgery for histological validation. Patients will be recruited over a 2-year period and followed up to 2 years to ascertain clinical outcomes. Follow-up CMR will be performed 12 months following AVR, and echocardiography with deformation analysis will be performed 3, 12, and 24 months following AVR. The study primary outcome is a composite of all-cause mortality and major adverse cardiovascular events. DISCUSSION: Despite continuous effort of research community there is still a lack of early predictors of left ventricular decompensation in AS, which could improve patient risk stratification and guide the optimal timing for aortic valve intervention, before irreversible left ventricular damage occurs. Advanced cardiac imaging and CMR derived markers of diffuse myocardial fibrosis could be utilized for this purpose. FIB-AS study is intended to invasively and non-invasively assess diffuse myocardial fibrosis in AS patients and investigate its prognostic significance in post-interventional outcomes. The results of the study will expand the current knowledge of cardiac remodeling in AS and will bring additional data on myocardial fibrosis and its clinical implications following AVR. ETHICS/DISSEMINATION: The study has full ethical approval and is actively recruiting patients. The results will be disseminated through scientific journals and conference presentations. TRIAL REGISTRATION: ClinicalTrials.govNCT03585933. Registered on 02 July 2018