scholarly journals Antiarrhythmic Effect of Sacubitril-Valsartan: Cause or Consequence of Clinical Improvement?

2019 ◽  
Vol 8 (6) ◽  
pp. 869 ◽  
Author(s):  
António Valentim Gonçalves ◽  
Tiago Pereira-da-Silva ◽  
Ana Galrinho ◽  
Pedro Rio ◽  
Luísa Moura Branco ◽  
...  

Sacubitril/Valsartan (LCZ696) reduced sudden cardiac death in the PARADIGM-HF trial. However, the mechanism by which LCZ696 reduces ventricular arrhythmias remains unclear. The aim of this study was to compare electrocardiographic (ECG) parameters and mechanical dispersion index, assessed by left ventricular (LV) global longitudinal strain (GLS), before and after LCZ696 therapy. We prospectively evaluated chronic Heart Failure (HF) patients with LV ejection fraction ≤40%, despite optimal medical and device therapy, in which LCZ696 therapy was started, while no additional HF treatment was expected to change. ECG and transthoracic echocardiographic data were gathered in the week before starting LCZ696 and at six months of therapy. A semiautomated analysis of LV GLS was performed and mechanical dispersion index was defined as the standard deviation from 16 time intervals corresponding to each LV segment. Of the 42 patients, 35 completed the six month follow-up, since two patients died and five discontinued treatment for adverse events. QTc interval (451.9 vs. 426.0 ms, p < 0.001), QRS duration (125.1 vs. 120.8 ms, p = 0.033) and mechanical dispersion index (88.4 vs. 78.1 ms, p = 0.036) were significantly reduced at six months. LCZ696 therapy is associated with a reduction in QTc interval, QRS duration and mechanical dispersion index as assessed by LV GLS.

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A A Valentim Goncalves ◽  
A Galrinho ◽  
T Pereira-Da-Silva ◽  
L Moura Branco ◽  
P Rio ◽  
...  

Abstract Introduction Sacubitril/Valsartan (LCZ696) significantly reduced sudden cardiac death in the PARADIGM-HF trial. However, there is little published data regarding the possible explanations for the antiarrhythmic effects found with LCZ696 therapy. Previous trials have shown that mechanical dispersion by strain echocardiography can predict arrhythmic events in Heart Failure (HF) patients. The aim of this study was to compare electrocardiographic (ECG) parameters and mechanical dispersion index with left ventricular (LV) global longitudinal strain (GLS) analysis before and after LCZ696 therapy. Methods Prospective evaluation of chronic HF patients with LV ejection fraction ≤ 40% despite optimized standard of care therapy, in which LCZ696 therapy was started and no additional HF treatment was expected to change. ECG and transthoracic echocardiographic data were gathered in the week before starting LCZ696 therapy and 6 months after therapy. A semiautomated analysis of LV GLS was made and mechanical dispersion index was defined as the standard deviation from the 16 time intervals corresponding to each LV segment. Results Of the 42 patients, 35 (83.3%) completed the 6 months of follow-up, since 2 (4.8%) patients died and 5 (11.9%) discontinued treatment for adverse events. Mean age was 58.6 ± 11.1 years. QTc interval (451.9 vs 426.0msec, p &lt; 0.001) and QRS interval (125.1 vs 120.8msec, p = 0.033) were reduced after 6 months of LCZ696 therapy. Mechanical dispersion index (88.4 vs 78.1msec, p = 0.036) was also significantly reduced after therapy. Conclusion LCZ696 therapy is associated with antiarrhythmic effects with a reduction in QTc and QRS intervals in ECG and a reduction in mechanical dispersion index as assessed by LV GLS. Abstract P1433 Figure.


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A I Scarlatescu ◽  
S Onciul ◽  
D Zamfir ◽  
A Pascal ◽  
M Dorobantu

Abstract Funding Acknowledgements This work was supported by CREDO Project - ID: 49182, financed through the SOP IEC -A2-0.2.2.1-2013-1 cofinanced by the ERDF. Background Left ventricule (LV) function plays an important role in the pathophysiology of decompensation after acute ST elevation myocardial infarction (STEMI). LV remodeling (LVR) after STEMI is associated with development of heart failure, predicting poor clinical outcome therefore its identification is of clinical importance to set up preventive strategies. Prediction of the left ventricular remodeling (LVR) after STEMI in patients treated by primary PCI is challenging. Purpose Finding an echocardiographic parameter that can predict left ventricular remodeling in time after STEMI. Materials and methods In this prospective study we included 30 consecutive patients, median age 60 (37-79), 76% male, with STEMI treated by primary PCI. We performed conventional 2D transthoracic echocardiography for all included patients. In addition to conventional parameters we measured LV global longitudinal strain (GLS) and LV mechanical dispersion using 2D speckle tracking imaging technique. For morphological and functional analysis of LV we used 3D echocardiography (volumes, LVEF) considering its superiority in assessment of LV. All measurements were performed at baseline (up to 7 days after STEMI) and at 5 year follow up. LVR was defined as an increase of over 15% of the LV end diastolic volume (LVEDV) in time, at 5 years after the STEMI. Results We obtained significant differences in time (up to 7 days after STEMI vs at 5 years) between 3D LVEF (46,48 vs 51,68, p = 0.002), LVEDV (97,12 vs 107,76, p = 0.000), 2D global strain (-11.76 vs - 14,1, p = 0.00), and mechanical dispersion (65,06 vs 57,66, p = 0.00) in all patients. LV remodeling at 5 years (15% increase in LVEDV) was observed in 36,6% of the included patients. At 5 years follow up, LVEDV mean value in the remodeling group was 130 ml and in the no remodeling group 90,21 ml (p = 0.002), 3D LVEF was 48,18 vs 54,42 (p = 0.05), global strain was - 12,33 vs -15,35 (p = 0.02) and LV mechanical dispersion 66,27 vs 55,55 (p = 0.05). Therefore patients with LV remodeling in time had lower LVEF, lower global strain and higher LV mechanical dispersion at baseline. Using ROC analysis we identified two cut off values, one of -11.55 for global LV strain measured at baseline (Sb 81.8%, Sp 77%, AUC 0.776, CI 95%, p = 0.022) and the other one of 63.7 for LV mechanical dispersion at admission (Sb 72,7%, Sp 62%, AUC 0.734, p 0.05) to discriminate between patients with or without LV adverse remodeling at 5 years after STEMI. We also found, using regression analysis, that GLS and LV mechanical dispersion are able to predict LV remodeling in time. Conclusion Global longitudinal strain and left ventricular mechanical dispersion measured in the acute phase can predict which patient is likely to undergo LV remodeling at 5 years after STEMI. GLS and LV dispersion could be used as predictors for future LV adverse remodeling after STEMI. Larger scale studies are needed to validate these findings.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Koziel ◽  
J Boidol ◽  
J Klys ◽  
K Miszalski-Jamka ◽  
Z Kalarus ◽  
...  

Abstract Background Myocarditis may be a challenging diagnosis because of diversity of clinical presentations. Thus, the clinical course and ventricular remodelling in this disease seems to be unpredictable. Aims To assess predictors of left ventricular remodelling in patients after active myocarditis. Methods Database from a high-volume, tertiary cardiology center was analysed to identify patients with active myocarditis, based on clinical presentation and ≥1 diagnostic criteria from different categories (including electrocardiography/ holter, elevated troponin T/I levels, functional or structural abnormalities on cardiac imaging or tissue characterization by cardiac magnetic resonance) between 2016 and 2019. Left ventricle global longitudinal strain (GLS), mechanical dispersion (standard deviation of time to peak longitudinal strain derived from all left ventricle segments in 3 apical views) were calculated. Response (left ventricular positive remodeling measured by transthoracic echocardiography) was defined as end-systolic volume (ESV) reduction ≥15% from a baseline value or end-diastolic volume (EDV) reduction ≥15%. Results 61 consecutive patients were enrolled. The median follow-up was 1.4 years (range: 0.3–4.0). During entire follow-up period mortality rate in patients was 1.6%. Multivariate Cox regression model including significant baseline differences as covariates reported that QRS durations (HR 1.31, 95% CI 1.17–1.57, P=0.049) and mechanical dispersion (HR 1.03, 95% CI 1.01–1.07, P=0.036) were independently associated with left ventricular positive remodelling with ESV reduction. Mechanical dispersion (HR 1.04, 95% CI 1.02–1.06, P=0.040) was independently associated with left ventricular positive remodelling with EDV reduction. Conclusions Mechanical dispersion and QRS duration are independent predictors of left ventricular remodelling in patients after active myocarditis. Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Juricic ◽  
O Petrovic ◽  
M Tesic ◽  
M Dobric ◽  
M Dikic ◽  
...  

Abstract Background Percutaneous coronary intervention of chronic total occlusion (PCI CTO) can reduce angina and the need for bypass surgery, however, it is still not clear how it effects the myocardial function. Conventional echocardiography is subjective and experience-dependent while tissue Doppler imaging together with strain imaging provides a more objective assessment of myocardial contractility. Purpose Our aim was to access the effectiveness of percutaneous coronary intervention (PCI) along with optimal medical therapy (OMT) on myocardial function. Methods We compared two groups of patients. The first group of patients underwent PCI CTO with OMT while the second group of patients only received OMT (control group). The echocardiographic exam was performed before randomization and after 24 months of follow-up. Doppler time intervals- isovolumetric relaxation time (IVRT), isovolumetric contraction time (IVCT) and ejection time (ET) were measured from mitral inflow and left ventricular outflow Doppler tracings. Myocardial performance index (MPI) is equal to the sum of the IVRT and IVCT divided by the ET. Velocity of early mitral filling wave (E) was measured and divided by average peak early diastolic annular velocity (e'). Peak longitudinal strain was assessed in 17 left ventricular segments. Time intervals from start Q/R on electrocardiogram to peak negative strain during the cardiac cycle were assessed. Mechanical dispersion was defined as the standard deviation of this time interval from 17 left ventricular segments, reflecting myocardial contraction heterogeneity Results Comparing the groups at follow up, there was no significant change in ejection fraction (EF), diastolic function, and mechanical dispersion, however, there was improvement in GLS and MPI (Table 1). Conclusion Global longitudinal strain as a parameter of systolic function and Myocardial performance index as a parametar of global systolic and diastolic function are sensitive markers that can detect subtle improvement in myocardial function after recanalisation of CTO. Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A A Valentim Goncalves ◽  
A Galrinho ◽  
T Pereira-Da-Silva ◽  
L Moura Branco ◽  
P Rio ◽  
...  

Abstract Introduction Myocardial work (MW) is a new transthoracic echocardiographic (TTE) parameter that enhances the information provided through left ventricular (LV) global longitudinal strain (GLS), allowing to investigate LV performance even in cases of changes in afterload. None is known about the effects of Sacubitril-Valsartan (LCZ696) therapy in MW parameters. Purpose Compare the changes in MW parameters between ischemic and non-ischemic segments after LCZ696 therapy. Methods The study was a prospective evaluation of chronic Heart Failure (HF) patients with optimized standard of care therapy and LV ejection fraction ≤40%, in which LCZ696 therapy was started and no other HF treatment was expected to change. A TTE study was performed before and 6 months after LCZ696 therapy, using the GE Vivid E95 ultrasound system. A semiautomated analysis of GLS was performed after two-dimensional images were acquired in the standard apical 4-, 3- and 2 chamber views. MW and related indices were estimated using custom software. Two groups were created according to the 17 segment model TTE study before LCZ696 therapy: G1 (ischemic group): dyskinesia/akinesia/hypokinesia segments in patients with ischemic HF etiology; G2 (non-ischemic group): normokinesia segments in patients with ischemic and all segments in patients with non-ischemic HF etiology; Results Of the 42 patients, 35 (83.3%) completed the six-months follow-up with LCZ696, since 2 patients (4.8%) died and 5 patients (11.9%) discontinued treatment for adverse events. Mean age was 58.6 ± 11.1 years, with ischemic etiology in 15 (42.9%), resulting in a total of 26.5% segments for G1. Baseline global MW index (GWI) had no statistical difference between G1 and G2 (566.1 VS 584.8mmHg%, p = 0.257), but baseline MW efficiency (GWE) were significantly lower in G1 (71.9 VS 78.8%, p &lt; 0.001). The table represents the mean values for MW parameters in G1 and G2 before and 6 months after LCZ696 therapy, with a significantly increase in GWI and GWE values in both groups. Despite no difference in the increase in GWE (p = 0.872), the increase in GWI were higher in G2 than G1 (p &lt; 0.001). Conclusion MW seems to be a new tool providing signs of reverse remodelling and better cardiac performance in ischemic and non-ischemic segments after LCZ696 therapy. Table 1 Time 0 6 months p GWI in ischemic segments (mmHg%) 566.1 ± 364.0 696.5 ± 445.2 &lt;0.001 GWE in ischemic segments (%) 71.9 ± 25.0 78.9 ± 19.1 0.009 GWI in non-ischemic segments (mmHg%) 584.8 ± 434.3 812.3 ± 442.0 &lt;0.001 GWE in non-ischemic segments (%) 78.8 ± 21.2 85.7 ± 15.8 0.004 MW data before and after six months of LCZ696 therapy


Open Heart ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. e001738
Author(s):  
Alessia Quattrone ◽  
Oyvind H Lie ◽  
Eirik Nestaas ◽  
Charlotte de Lange ◽  
Kirsti Try ◽  
...  

ObjectiveAdults operated for tetralogy of Fallot (TOF) have high risk of ventricular arrhythmias (VA). QRS duration >180 ms is an established risk factor for VA. We aimed to investigate heart function, prevalence of arrhythmias and sex differences in patients with TOF at long-term follow-up.MethodsWe included TOF-operated patients≥18 years from our centre’s registry. We reviewed medical records and the most recent echocardiographic exam. VA was recorded on ECGs, 24-hour Holter registrations and from implantable cardioverter defibrillator.ResultsWe included 148 patients (age 37±10 years). Left ventricular global longitudinal strain (LV GLS, −15.8±3.1% vs −18.8±3.2%, p=0.001) and right ventricular (RV) GLS (−15.8±3.9% vs −19.1±4.1%, p=0.001) were lower in men at all ages compared with women. Higher RV D1 (4.3±0.5 cm vs 4.6±0.6 cm, p=0.01), lower ejection fraction (55%±8% vs 50%±9%, p=0.02), lower RV GLS (−18.1±4.0 ms vs −16.1±4.8 ms, p=0.04) and N-terminal pro-brain natriuretic peptide (NT-proBNP) over reference range (n=27 (23%) vs n=8 (77%), p<0.001) were associated with higher incidence of VA. QRS duration was longer in men (151±30 ms vs 128±25 ms, p<0.001). No patients had QRS duration >180 ms. QRS duration did not differ in those with and without VA (143±32 ms vs 137±28 ms, p=0.06).ConclusionsOur results confirmed reduced RV function in adults operated for TOF. Male patients had impaired LV and RV function expressed by lower LV and RV GLS values at all ages. Reduced cardiac function and elevated NT-proBNP were associated with higher incidence of VA and may be important in risk assessment.


2021 ◽  
pp. neurintsurg-2020-017155
Author(s):  
Alexander M Kollikowski ◽  
Franziska Cattus ◽  
Julia Haag ◽  
Jörn Feick ◽  
Alexander G März ◽  
...  

BackgroundEvidence of the consequences of different prehospital pathways before mechanical thrombectomy (MT) in large vessel occlusion stroke is inconclusive. The aim of this study was to investigate the infarct extent and progression before and after MT in directly admitted (mothership) versus transferred (drip and ship) patients using the Alberta Stroke Program Early CT Score (ASPECTS).MethodsASPECTS of 535 consecutive large vessel occlusion stroke patients eligible for MT between 2015 to 2019 were retrospectively analyzed for differences in the extent of baseline, post-referral, and post-recanalization infarction between the mothership and drip and ship pathways. Time intervals and transport distances of both pathways were analyzed. Multiple linear regression was used to examine the association between infarct progression (baseline to post-recanalization ASPECTS decline), patient characteristics, and logistic key figures.ResultsASPECTS declined during transfer (9 (8–10) vs 7 (6-9), p<0.0001), resulting in lower ASPECTS at stroke center presentation (mothership 9 (7–10) vs drip and ship 7 (6–9), p<0.0001) and on follow-up imaging (mothership 7 (4–8) vs drip and ship 6 (3–7), p=0.001) compared with mothership patients. Infarct progression was significantly higher in transferred patients (points lost, mothership 2 (0–3) vs drip and ship 3 (2–6), p<0.0001). After multivariable adjustment, only interfacility transfer, preinterventional clinical stroke severity, the degree of angiographic recanalization, and the duration of the thrombectomy procedure remained predictors of infarct progression (R2=0.209, p<0.0001).ConclusionsInfarct progression and postinterventional infarct extent, as assessed by ASPECTS, varied between the drip and ship and mothership pathway, leading to more pronounced infarction in transferred patients. ASPECTS may serve as a radiological measure to monitor the benefit or harm of different prehospital pathways for MT.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Kupczynska ◽  
D Miskowiec ◽  
B Michalski ◽  
L Szyda ◽  
K Wierzbowska-Drabik ◽  
...  

Abstract Background Atrial fibrillation (AF) impairs mechanical function of the heart, especially atria and restoration of sinus rhythm (SR) leads to improvement of mechanics. The predicting role of changes in strain parameters for AF recurrence is not established yet. Purpose To analyse changes in left atrial (LA) and left ventricular (LV) mechanical function after conversion to SR and their prognostic values for AF recurrence during 24 months follow-up. Methods Prospective study involved 59 patients after successful electrical cardioversion (EC) because of nonvalvular AF (mean age 65±4 years, 47% female). Speckle tracking analysis (STE) was applied to calculate longitudinal strain of LV and LA before EC and within 24 hours after restoration of SR and additionally total left heart strain (TS) defined as a sum of absolute peak LV and LA strain. We calculated change in strain between AF and SR analyses expressed as delta (Δ). During follow-up we noticed AF recurrence in 42 (71%) patients, most of them (93%) during 1st year after EC. Median time of AF recurrence was 3 months. Results We noticed significant immediate post-EC improvement in peak LA longitudinal strain (PALS) and LV global longitudinal strain (LVGLS) (table). Unlike CHA2DS2-VASc score, strain parameters were predictors of AF recurrence. Every 1% increment in ΔLVGLS was related with 13% increase in AF recurrence risk (p=0.02) and every 1% increment in ΔPALS and ΔTS were related with 9% decrease in AF recurrence risk (p=0.007 and p=0.0014, respectively). Multivariate analysis revealed ΔTS as a strongest predictor with 9% decrease in AF risk per every 1% increment. The criterion of ΔTS ≤7.5% allows to predict AF recurrence with 81% sensitivity and 63% specificity. Conclusions Speckle tracking measurements are able to detect early mechanical changes in LA even within 24 hours of SR and these absolute changes in LVGLS as well as PALS can predict AF recurrence, with optimal stratification by novel parameter - TS. Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Boidol ◽  
M Koziel ◽  
K Miszalski-Jamka ◽  
J Klys ◽  
Z Kalarus ◽  
...  

Abstract Background The clinical course and ventricular remodeling in inflammatory myocardial disease could be unpredictable. No single functional parameter has been confirmed as a powerful predictor of clinical course and functional recovery assessment in patients with acute inflammatory myocardial disease. Purpose The aim of the study was to assess the mechanical properties of the myocardium in patients with active myocarditis at baseline and follow-up. Methods Database from a high volume, tertiary cardiology center was analysed to identify patients with active myocarditis, based on clinical presentation and ≥1 diagnostic criteria from different categories (including electrocardiography/holter, elevated troponin T/I levels, functional or structural abnormalities on cardiac imaging or tissue characterization by cardiac magnetic resonance) between 2016 and 2019. Conventional and speckle tracking echocardiography including global longitudinal strain (GLS) mechanical dispersion (MD) was completed at baseline and at 17±13 months follow-up. MD was calculated as a standard deviation of time to peak longitudinal strain derived from all left ventricle segments in 3 apical views. Results 61 consecutive patients [50 M, 11F, end-diastolic volume 212±84 ml, end-systolic volume 130±90ml, ejection fraction (EF) 42±16%] were enrolled. During the entire follow-up 1 patient died at early observation. Implantable cardioverter-defibrillator was implanted in 5 patients (primary prevention 4, secondary 1), cardiac resynchronization therapy pacemaker in 1 patient. Despite of significant global improvement (EF 42±16% vs 52±10%, p&lt;0.001) the limited regional improvement was noticed (GLS 14±6% vs 15±4%, p = NS; MD 47±18 ms vs 45±20 ms, p=NS) in all patients at 17±13 months follow-up. There was a strong negative association between GLS and MD at baseline (Figure 1), and slightly weaker at follow-up (R=0.47, Pearson's correlation). Moreover, the GLS correlated well the change of MD in each individual patient. Conclusions Mechanical dispersion and global longitudinal strain may serve as an additional markers of myocardial damage and potential predictive markers in non ischemic cardiomyopathy patients with proven inflammatory origin. Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Triantafyllou ◽  
R Monteiro ◽  
A Protonotarios ◽  
T Gossios ◽  
P Elliott ◽  
...  

Abstract Introduction Early detection of affected family relatives of patients with dilated cardiomyopathy (DCM) is essential in order to guide follow up, outcomes and initiate early treatment. Myocardial work analysis is a novel method which integrated strain imaging and blood pressure and has the potential to identify patients with subclinical disease. Purpose We analysed myocardial work in family relatives of DCM patients with positive genotype but negative phenotype in order to identify whether myocardial work can identify early changes. Methods Seventy-four family relatives of DCM patients attending for screening were examined. All individuals were asymptomatic with either positive (45/74, G+) or negative (29/74, G-) genotype and no echocardiographic evidence of left ventricular dilatation or systolic impairment. Non-invasive myocardial work analysis using two-dimensional (2D) speckle tracking echocardiography was analysed. Global longitudinal strain (GLS) was measured by the same vendor specific software used for myocardial work analysis. Left ventricular (LV) ejection fraction (EF) was measured with the Simpson's biplane method. The peak systolic arm cuff blood pressure (BP) measurement at the time of echocardiography was used for the myocardial work study. Results In total we included 74 individuals (37±15 years old, 50.7% women) with mean systolic and diastolic BP of 121.3±14 and 73.2±10 mmHg respectively, mean EF was 58±5% and mean GLS at 18.4±2.5%. G+ individuals had pathogenic and very likely pathogenic mutations in 8 different genes (TTN, BAG3, DSP, FLNC, LMNA, DMD, RBM20, TPM1). There was no difference in age, systemic hypertension, diabetes or medical treatment between the 2 groups. No significant difference was found among G+ and G- individuals in mean systolic and diastolic BP (121.2±14.7 vs 121.2±15.2 mmHg), mean EF (57.3±5 vs 59.1±4%), GLS (−18.2±1.5 vs −18.6±2.9%), mean global work index (1818±403 vs 1928±295 mmHg%) and global constructive work (2192±464 vs 2260±318 mmHg%). However, we found significant reduction of the global work efficiency (GWE) with a GWE of 94.4±2.7% in the G+ versus 95.9±1.6% in the G- individuals (p 0.02). Moreover, the global wasted work (GWW) was increased in the G+ with a GWW of 111±58 mmHg% versus 82±41 mmHg% in the G- individuals (p 0.03). Conclusion DCM gene carriers show, early on, decreased myocardial work efficiency and increased wasted work compared to unaffected family members, which appears to be earlier than other parameters such as EF and GLS. Myocardial work analysis could potentially recognize individuals showing early cardiac involvement and guide closer follow up and early initiation of treatment. Funding Acknowledgement Type of funding source: None


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