Change In Left Ventricular End-systolic Volume Research Articles

Mesenchymal stromal cells to treat patients with non-ischaemic heart failure: Results from SCIENCE II pilot study.

Allogeneic stem cell therapy is more logistically suitable compared with autologous cell therapy for large-scale patient treatment. We aim to investigate the clinical safety and efficacy profile of the allogeneic adipose tissue derived mesenchymal stromal cell product (CSCC_ASC) as an add-on therapy in patients with chronic non-ischaemic heart failure with reduced left ventricular ejection fraction (HFrEF)<40%. This is a single-centre investigator-initiated randomized phase I/II study with direct intra-myocardial injections of 100 million allogeneic CSCC_ASC. A total of 30 HFrEF patients with New York Heart Association (NYHA) class ≥II despite optimal anticongestive heart failure medication and plasma NT-proBNP>300pg/mL (>35pmol/L) were included and randomized 2:1 to CSCC_ASC or standard care. The primary endpoint left ventricular end systolic volume (LVESV) and other echo related parameters were analysed by an investigator blinded for treatment allocation. No difference in serious adverse events was observed between groups. LVESV decreased significantly from baseline to 6months follow-up in the ASC group (153.7±53.2mL and 128.7±45.6mL, P<0.001) and remained unchanged in the standard care group (180.4±39.4mL and 186.7±48.9mL, P=0.652). There was a significant difference between the groups in LVESV change (31.3±11.0mL, P=0.009). The difference from baseline to follow-up between the two groups in left ventricular end diastolic volume (LVEDV) was 18.7±12.4mL, P=0.146 and in left ventricular ejection fraction (LVEF) -7.8±2.1%, P=0.001. Considering the baseline values of LVESV, LVEDV and LVEF as covariates, the difference between groups for change from baseline to follow-up resulted in a P-value of 0.056, 0.076, and 0.738, respectively. NYHA class and self-reported health did also improve significantly in the ASC group compared with the standard care group (0.7±0.2, P=0.001 and -12.8±5.3, P=0.025; respectively). There was no difference in NT-proBNP (-371±455pmol/L, P=0.422) or in 6min walk test (12±31m, P=0.695) between groups. Intramyocardial injections of allogeneic CSCC_ASC in patients with chronic non-ischaemic HFrEF was safe and improved LVESV, LVEF, NYHA class, and self-reported health compared with standard care group.

Temporal Changes in Extracellular Vesicle Hemostatic Protein Composition Predict Favourable Left Ventricular Remodeling after Acute Myocardial Infarction.

The subset of plasma extracellular vesicles (EVs) that coprecipitate with low-density lipoprotein (LDL-EVs) carry coagulation and fibrinolysis pathway proteins as cargo. We investigated the association between LDL-EV hemostatic/fibrinolysis protein ratios and post-acute myocardial infarction (post-AMI) left ventricular (LV) remodeling which precedes heart failure. Protein concentrations of von Willebrand factor (VWF), SerpinC1 and plasminogen were determined in LDL-EVs extracted from plasma samples obtained at baseline (within 72 h post-AMI), 1 month and 6 months post-AMI from 198 patients. Patients were categorized as exhibiting adverse (n = 98) or reverse (n = 100) LV remodeling based on changes in LV end-systolic volume (increased or decreased ≥15) over a 6-month period. Multiple level longitudinal data analysis with structural equation (ML-SEM) model was used to assess predictive value for LV remodeling independent of baseline differences. At baseline, protein levels of VWF, SerpinC1 and plasminogen in LDL-EVs did not differ between patients with adverse versus reverse LV remodeling. At 1 month post-AMI, protein levels of VWF and SerpinC1 decreased whilst plasminogen increased in patients with adverse LV remodeling. In contrast, VWF and plasminogen decreased whilst SerpinC1 remained unchanged in patients with reverse LV remodeling. Overall, compared with patients with adverse LV remodeling, higher levels of SerpinC1 and VWF but lower levels of plasminogen resulted in higher ratios of VWF:Plasminogen and SerpinC1:Plasminogen at both 1 month and 6 months post-AMI in patients with reverse LV remodeling. More importantly, ratios VWF:Plasminogen (AUC = 0.674) and SerpinC1:Plasminogen (AUC = 0.712) displayed markedly better prognostic power than NT-proBNP (AUC = 0.384), troponin-I (AUC = 0.467) or troponin-T (AUC = 0.389) (p < 0.001) to predict reverse LV remodeling post-AMI. Temporal changes in the ratios of coagulation to fibrinolysis pathway proteins in LDL-EVs outperform current standard plasma biomarkers in predicting post-AMI reverse LV remodeling. Our findings may provide clinical cues to uncover the cellular mechanisms underpinning post-AMI reverse LV remodeling.

Cardiac resynchronization therapy outcomes with left ventricular lead concordant with latest mechanical activation: A meta-analysis.

For cardiac resynchronization therapy (CRT), image-guided approaches targeting left ventricular (LV) lead placement at the site of latest mechanical activation had inconsistent outcomes. We examined evidence for improved CRT outcomes when LV lead placement concordant with latest mechanical activation occurred. A review of EMBASE and PubMed was performed for randomized controlled trials or prospective observational studies from October 2008 through October 2020 comparing outcomes with concordant versus discordant LV lead placement. Meta-analyses were performed to assess the association between concordance and death, death or heart failure (HF) hospitalization,≥15% reduction in LV end systolic volume (LVESV), and changes in LVESV or ejection fraction (LVEF). From 5897 citations, nine publications (eight studies) with 1355 patients were selected; 975 with a concordant LV lead and 380 with a discordant lead. Mean age was 66-68 years, 82% were male, and 64% had ischemic cardiomyopathy. Meta-analyses demonstrated a statistically significant reduction in death/HF hospitalization at 2 years (OR 0.38; 95% CI 0.16, 0.92) and LVESV at 6 months (mean difference [MD] -13.4%; 95% CI -6.7%, -20.0%), and an increase in LVEF (MD 4.03; 95% CI 0.77, 7.30) with the concordant LV lead. There were trends toward decreased death at 2 years (OR 0.49; 95% CI 0.19, 1.23) and≥15% reduction in LVESV at 6 months (OR 3.81; 95% CI 0.24, 61.24) with concordant LV lead placement. A concordant LV lead was associated with better CRT outcomes. Further study of feasible methods to achieve LV lead concordance is needed.

Comparison between his-bundle pacing and biventricular pacing as cardiac resynchronization therapy for heart failure patients: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac resynchronization therapy (CRT) has demonstrated significant improvements in cardiovascular outcomes of selected heart failure patients. However, conventional biventricular CRT implantation can be challenging due to unfavorable coronary sinus anatomy, leads to lead instability, poor capture, and insufficient cardiac resynchronization. His-bundle pacing has gained interest as alternative strategy for patients underwent biventricular CRT implantation when coronary sinus lead implantation is unsuccesful or in non-responder cases. Purpose This study aims to compare the efficacy of his-bundle pacing and biventricular pacing in improving electrocardiographic, echocardiographic, and clinical parameters of heart failure patients that required resynchronization therapy. Methods A search for eligible studies was conducted until August 2021 on three databases (PubMed, ScienceDirect, ProQuest). Included studies were evaluated for risk of bias. Our primary outcomes of interest were mean difference in QRS duration, left ventricular ejection fraction (LVEF), and change in systolic blood pressure (SBP). We also investigated left ventricular activation time, left ventricular dyssynchrony index, left ventricular end-systolic volume (LVESV), New York Heart Association (NYHA) functional class, 6-minute walk test, quality of life, heart failure hospitalization and cardiovascular or all cause death. Review Manager (RevMan) 5.4 was utilized to compute mean differences. Results We identified five studies from 2010 to 2019, involving 95 heart failure patients underwent CRT implantation. Pooled analysis showed that his-bundle pacing resulted in significant narrowing of QRS duration compared to biventricular pacing [Mean Difference -23.17 ms (95% CI -36.10, -10.24; p=0.0004; I2=0.63)]. Left ventricular activation time and left ventricular dyssynchrony index were significantly improved in his bundle pacing. There were no significant differences of changes in LVEF, LVESV, and SBP. Clinical parameters such as NYHA functional class, 6-minute walk test, and quality of life were significantly improved in both pacing modality. No significant difference in heart failure hospitalization and cardiovascular or all cause mortality. Conclusion His-bundle pacing delivers better decrease of QRS duration, also reduction in left ventricular activation time and left ventricular dyssynchrony index compared to biventricular pacing. These suggests that his-bundle pacing is a reasonable alternative option for cardiac resynchronization therapy.

Aetiology of Heart Failure, Rather than Sex, Determines Reverse LV Remodelling Response to CRT.

Introduction: Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure with reduced ejection fraction (HFrEF). Women appear to respond differently to CRT, yet it remains unclear whether this is inherent to the female sex itself, or due to other patient characteristics. In this study, we aimed to investigate sex differences in response to CRT. Methods: This is a post-hoc analysis of a prospective, multicenter study (MARC) in the Netherlands, studying HFrEF patients with an indication for CRT according to the guidelines (n = 240). Primary outcome measures are left ventricular ejection fraction (LVEF) and left ventricular end systolic volume (LVESV) at 6 months follow-up. Results were validated in an independent retrospective Belgian cohort (n = 818). Results: In the MARC cohort 39% were women, and in the Belgian cohort 32% were women. In the MARC cohort, 70% of the women were responders (defined as >15% decrease in LVESV) at 6 months, compared to 55% of men (p = 0.040) (79% vs. 67% in the Belgian cohort, p = 0.002). Women showed a greater decrease in LVESV %, LVESV indexed to body surface area (BSA) %, and increase in LVEF (all p < 0.05). In regression analysis, after adjustment for BSA and etiology, female sex was no longer associated with change in LVESV % and LVESV indexed to BSA % and LVEF % (p > 0.05 for all). Results were comparable in the Belgian cohort. Conclusions: Women showed a greater echocardiographic response to CRT at 6 months follow-up. However, after adjustment for BSA and ischemic etiology, no differences were found in LV-function measures or survival, suggesting that non-ischemic etiology is responsible for greater response rates in women treated with CRT.

Abstract 13731: Randomized Trial of CMR Guidance for Cardiac Resynchronization Therapy: Findings in Nonischemic Cardiomyopathy From an Interim Analysis

Introduction: Cardiac resynchronization therapy (CRT) response rates in unselected cohorts are suboptimal. Cardiac magnetic resonance (CMR) provides high-quality imaging of strain and scar, and post-CRT CMR offers reliable assessment of left ventricular (LV) reverse remodeling. Hypothesis: Cardiac magnetic resonance (CMR) guidance for CRT will increase CRT response rates, particularly in nonischemic cardiomyopathy (NICM). Methods: Patients were randomized 1:1 to standard CRT or CMR guidance for CRT using circumferential strain from Displacement Encoding with Stimulated Echoes (DENSE) and scar (late gadolinium enhancement [LGE]) by CMR. The primary endpoint is the percent change in LV end-systolic volume (LVESV) calculated from CMRs before CRT and 6 months after CRT. A pre-specified interim analysis by cardiomyopathy type was performed after completion of enrollment of 45 of the projected 90 patients needed for adequate power. Results: Of 45 patients enrolled (age 65.9 +/- 10.3 years, 29% female), two patients did not undergo a CRT procedure, and the LV lead could not be placed in one patient. Of the remaining 42 patients, 26/42 had NICM and 21/42 were randomized to CMR guidance. In a linear regression model for the primary endpoint adjusted for baseline QRS duration (p=0.04) and cardiomyopathy type (p=0.01), a favorable trend for the intervention on response was noted (p=0.06). Box plots demonstrate a significant difference in the primary endpoint among NICM patients (p=0.03) and a favorable trend for QRS shortening (0.07) in NICM patients (Figure). In all patients (including ICM patients), the overall p-value for the intervention relative to the primary endpoint was 0.08. Conclusion: An interim analysis in CRT patients with NICM demonstrated a favorable effect of CMR guidance on LV reverse remodeling after CRT, as assessed with post-CRT CMRs. Enrollment is continuing to evaluate the effect of the intervention on the entire cohort and other endpoints.

Intracardiac conduction time as a predictor of cardiac resynchronization therapy response: Results of the BIO|SELECT pilot study.

BackgroundQuadripolar left ventricular (LV) leads are capable of sensing and pacing the left ventricle from 4 different electrodes, which may potentially improve patient response to cardiac resynchronization therapy (CRT).ObjectiveWe measured 3 different time intervals: right ventricular (RV)-sensed to LV-sensed during intrinsic rhythm (RVs-LVs), RV-paced to LV-sensed (RVp-LVs), and LV-paced to LV-sensed (LVp-LVs, between distal [LV1] and proximal pole on a quadripolar LV lead), and assessed their association with CRT response in terms of LV end-systolic volume (LVESV) and a composite benefit index (CBI) comprising LVESV, LV ejection fraction (LVEF), brain natriuretic peptide level, and NYHA class.MethodsA CRT-defibrillator system with quadripolar LV lead was implanted in 196 patients (mean age 69 years, mean LVEF 30%, left bundle-branch block [LBBB] 58%). Conduction intervals were measured before hospital discharge. At baseline and 7-month follow-up, echocardiographic and other components of CBI were determined.ResultsThe mean RVs-LV1s, RVp-LV1s, and LVp-LVs delays were 68 ± 38 ms, 132 ± 34 ms, and 99 ± 31 ms, respectively. From baseline to 7 months, LVESV decreased by 17.3% ± 28.6%. The RVs-LV1s interval correlated stronger with CBI (R2 = 0.12, P < .00001) than with LVESV change (R2 = 0.05, P = .006). In contrast, RVp-LV1s did not correlate and LVp-LVs correlated only weakly with CRT response. The subgroup of patients (44%) with LBBB and RVs-LV1s above the lower quartile (≥34 ms) showed the greatest response to CRT.ConclusionThe RVs-LVs interval during intrinsic rhythm is relevant for CRT success, whereas RVp-LVs and LVp-LVs intervals did not predict CRT response.

Clinical outcomes of upgrade to versus de novo cardiac resynchronization therapy in mild heart failure patients with atrioventricular block

BackgroundIndication for de novo cardiac resynchronization therapy (CRT) has been recommended in mild heart failure (HF) patients with left ventricular (LV) ejection fraction (LVEF) <50% and atrioventricular block (AVB). In contrast, the indication of CRT upgrade from right ventricular pacing (RVP) has been limited to severe HF patients with LVEF≤35% and AVB. This study examined LV volumetric responses and clinical outcomes in mild HF patients with AVB who underwent CRT upgrade, compared with those of de novo CRT patients. MethodsThis retrospective study focused on patients with CRT due to AVB, mild HF at New York Heart Association class II and LVEF<50%. A total of 58 patients were divided into two groups: (1) 27 patients with CRT upgrade from RVP>40% (Upgrade group, UG), and (2) 31 patients with de novo CRT implantation (De novo group, DG). The echocardiographic assessment was performed at baseline and six months after CRT. The study endpoint was a combined endpoint with total mortality, HF hospitalization, or ventricular tachyarrhythmia events. ResultsAt six months after CRT, the LV end-systolic volume (LVESV) was significantly reduced in both groups (from 144.3±39.4 mL to 111.1±33.5 mL in UG, p<0.01; from 134.5±36.6 mL to 123.5±45.6 mL in DG, p<0.05); however, a significant improvement in LVEF was obtained in UG but not in DG (from 31.7±6.8% to 39.7±8.5% in UG, p<0.01; from 34.2±7.3% to 36.0±9.7% in DG, p=0.15). Consequently, the changes in LVESV and LVEF were significantly greater in UG than in DG. During the follow-up of 989 days, the survival rate for the composite events were similar between both groups (p=0.18). ConclusionsLV reverse remodeling was significantly greater in UG than DG, and the incidence of clinical composite events at mid-term follow-up was equivalent between UG and DG. CRT upgrade could be an acceptable indication in mild HF patients dependent on RVP.

Evaluation of the long-term effectiveness of cardiac resynchronization therapy

Aim. To determine quantitative criteria for assessing the therapeutic benefits and the most informative time frames after cardiac resynchronization therapy (CRT) to assess its long-term effectiveness (1, 2, 3 years of follow-up) based on retrospective analysis. To assess the CRT effectiveness, parameters of left ventricular (LV) reverse remodeling and signs characterizing the clinical CRT response were considered.Material and methods. This single-center, retrospective, non-randomized study included data from 278 patients with implanted CRT devices. Quantitative criteria for assessing CRT effectiveness were determined using a two-step cluster analysis of patients 1, 2, and 3 years after CRT by LV reverse remodeling parameters.Results. In the dataset with satisfactory division accuracy, after the first year, two clusters were identified, which are conventionally named as “non-responders” and “responders”. Two and three years after therapy, patients were classified into three clusters: “non-responders”, “responders” and “super-responders”. For the obtained clusters, we found cutoff values for LV reverse remodeling parameters, which can be used as criteria for response to therapy.The study identified the most informative time frames for assessing the postoperative CRT effectiveness 1, 2, 3 years after the surgery. At the same time, the clinical response to therapy is manifested earlier in comparison with the reverse LV remodeling.Despite the high divisibility of patients into responders and non-responders, predictive models of CRT effectiveness created using the available data from standard diagnostic protocols for heart failure patients have insufficient accuracy to be used for making decisions on therapy appropriateness. This circumstance indicates the need to receive additional data to improve the forecasting quality.Conclusion. The study revealed a period for assessing the clinical response and changes in LV reverse remodeling after CRT surgery, which is important for the optimal choice of postoperative therapy. It has been shown that in most cases, one year after surgery is sufficient to assess the clinical response, and the process of LV reverse remodeling can last up to two years on average.When assessing the CRT effectiveness by reverse remodeling, along with a change in LV end-systolic volume (ESV), it is necessary to take into account LV end-diastolic volume (EDV) changes. The change in LV ejection fraction showed a significantly lower value among the analyzed parameters in assessing the CRT effectiveness. Based on the cluster classification of patients, a dividing rule was established for responders and non-responders in the first and second years after surgery with an accuracy of 97%: a decrease in LV ESV and EDV by 9% or more compared to preoperative values.

Segment length in cine (SLICE) strain analysis: a practical approach to estimate potential benefit from cardiac resynchronization therapy

BackgroundSegment length in cine (SLICE) strain analysis on standard cardiovascular magnetic resonance (CMR) cine images was recently validated against gold standard myocardial tagging. The present study aims to explore predictive value of SLICE for cardiac resynchronization therapy (CRT) response.Methods and resultsFifty-seven patients with heart failure and left bundle branch block (LBBB) were prospectively enrolled in this multi-center study and underwent CMR examination before CRT implantation. Circumferential strains of the septal and lateral wall were measured by SLICE on short-axis cine images. In addition, timing and strain pattern parameters were assessed. After twelve months, CRT response was quantified by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). In contrast to timing parameters, strain pattern parameters being systolic rebound stretch of the septum (SRSsep), systolic stretch index (SSIsep-lat), and internal stretch factor (ISFsep-lat) all correlated significantly with LVESV change (R − 0.56; R − 0.53; and R − 0.58, respectively). Of all strain parameters, end-systolic septal strain (ESSsep) showed strongest correlation with LVESV change (R − 0.63). Multivariable analysis showed ESSsep to be independently related to LVESV change together with age and QRSAREA.ConclusionThe practicable SLICE strain technique may help the clinician to estimate potential benefit from CRT by analyzing standard CMR cine images without the need for commercial software. Of all strain parameters, end-systolic septal strain (ESSsep) demonstrates the strongest correlation with reverse remodeling after CRT. This parameter may be of special interest in patients with non-strict LBBB morphology for whom CRT benefit is doubted.

Rationale and methods of a randomized trial evaluating the effect of neprilysin inhibition on left ventricular remodelling.

AimsIn patients at high risk of heart failure following myocardial infarction (MI) as a result of residual left ventricular systolic dysfunction (LVSD), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan may result in a greater attenuation of adverse left ventricular (LV) remodelling than renin angiotensin aldosterone system inhibition alone, due to increased levels of substrates for neprilysin with vasodilatory, anti‐hypertrophic, anti‐fibrotic, and sympatholytic effects.MethodsWe designed a randomized, double‐blinded, active‐comparator trial to examine the effect of sacubitril/valsartan to the current standard of care in reducing adverse LV remodelling in patients with asymptomatic LVSD following MI. Eligible patients were ≥3 months following MI, had an LV ejection fraction ≤40% as measured by echocardiography, were New York Heart Association functional classification I, tolerant of an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker at equivalent dose of ramipril 2.5 mg twice daily or greater, and taking a beta‐blocker unless contraindicated or intolerant. Patients were randomized to sacubitril/valsartan (target dose 97/103 mg twice daily) or valsartan (target dose 160 mg twice daily). The primary endpoint will be change in LV end‐systolic volume indexed for body surface area measured using cardiac magnetic resonance imaging over 52 weeks from randomization. Secondary endpoints include other magnetic resonance imaging‐based metrics of LV remodelling, biomarkers associated with LV remodelling and neurohumoral activation, and change in patient well‐being assessed using a patient global assessment questionnaire.ConclusionsThis trial will investigate the effect of neprilysin inhibition on LV remodelling and the neurohumoral actions of sacubitril/valsartan in patients with asymptomatic LVSD following MI.

Sodium glucose cotransporter-2 inhibitor was associated with an improvement in left ventricular systolic function in patients with type 2 diabetes mellitus with impaired left ventricular systolic function.

AimsRecent studies indicated that sodium glucose cotransporter‐2 inhibitors (SGLT2i) reduced heart failure hospitalization in patients with type 2 diabetes mellitus (T2DM). However, whether SGTL2i can improve left ventricular (LV) systolic and diastolic function remained unclear. This study aimed to compare the change in echocardiographic parameters in T2DM patients receiving SGLT2i with a different baseline LV ejection fraction (LVEF). The change in echocardiographic parameters was also compared between T2DM patients treated with SGLT2i and those treated with dipeptidyl peptidase‐4 inhibitor (DPP4i).Methods and resultsThis multicentre cohort study consecutively enrolled 665, 119, and 132 T2DM patients treated with SGLT2i with a preserved (≥50%), moderately reduced (40–50%), and reduced baseline LVEF (<40%), respectively, with paired baseline and post‐treatment echocardiographic data available between 1 June 2016 and 31 May 2018. There were 212 patients treated with DPP4i with paired baseline and post‐treatment echocardiographic data available at the same time. For those patients treated with DPP4i, 45 patients had impaired baseline LVEF of <50%. Echocardiographic parameters, including LVEF, LV end‐diastolic volume, LV end‐systolic volume (LVESV), and LV diastolic function, were analysed at baseline and after treatment. After a median SGLT2i treatment period of 230 days, patients with reduced LVEF were associated with an improvement in LVEF from 29.4 ± 7.4% to 42.2 ± 15.2% (P < 0.0001) and decrease in LVESV from 133.2 ± 49.2 to 117.4 ± 60.1 mL (P = 0.0002). Patients with moderately reduced LVEF were associated with an improvement in LVEF from 44.8 ± 2.9% to 49.7 ± 12.4% (P < 0.0001) and decrease in LVESV from 90.7 ± 31.1 to 80.0 ± 36.2 mL (P = 0.0017). Patients with preserved LVEF did not show an improvement in LVEF and LVESV after SGLT2i treatment. There were no significant changes of LV end‐diastolic volume, LV diastolic function, and LV wall thickness in three study groups after SGLT2i treatment. In contrast, patients with impaired baseline LVEF (<50%) did not show any change in LVEF and LVESV after DPP4i treatment.ConclusionsSodium glucose cotransporter‐2 inhibitor was associated with an improvement in LV systolic function in patients with T2DM with reduced and moderately reduced LVEF. In contrast, DPP4i treatment was not associated with any improvement in LVEF among patients with impaired LVEF.

Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial

Elamipretide, a novel mitochondrial modulating agent, improves myocardial energetics; however, it is unknown whether this mechanistic benefit translates into improved cardiac structure and function in heart failure (HF) with reduced ejection fraction (HFrEF). The objective of this study was to evaluate the effects of multiple subcutaneous doses of elamipretide on left ventricular end systolic volume (LVESV) as assessed by cardiac magnetic resonance imaging. We randomized 71 patients with HFrEF (LVEF ≤ 40%) in a double-blind, placebo-controlled trial in a 1:1:1 ratio to receive placebo, 4 mg or 40 mg elamipretide once daily for 28 consecutive days. The mean age (standard deviation) of the study population was 65 ± 10 years, 24% were females, and the mean EF was 31% ± 7%. The change in LVESV from baseline to week 4 was not significantly different between elamipretide 4 mg (89.4 mL to 85 mL; difference, -4.4 mL) or 40 mg (77.9 mL to 76.6 mL; difference, -1.2 mL) compared with placebo (77.7 mL to 74.6 mL; difference, -3.8 mL) (4 mg vs placebo: difference of means, -0.3; 95% CI, -4.6 to 4.0; P = 0.90; and 40 mg vs placebo: difference of means, 2.3; 95% CI, -1.9 to 6.5; P = 0.28). Also, no significant differences in change in LVESV and LVEF were observed between placebo and either of the elamipretide groups. Rates of any study drug-related adverse events were similar in the 3 groups. Elamipretide was well tolerated but did not improve LVESV at 4 weeks in patients with stable HFrEF compared with placebo.

Passive leg raising combined with echocardiography could evaluate volume responsiveness in patients with septic shock

To assess the value of passive leg raising (PLR) combined with echocardiography in predicting volume responsiveness in patients with septic shock. Thirty septic shock patients with spontaneous respiration admitted to intensive care unit (ICU) of Tianjin First Center Hospital from July 2016 to August 2018 were enrolled. PLR and volume expansion (VE) were performed successively. The hemodynamic parameters including left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), stroke volume (SV) and left ventricular ejection fraction (LVEF) before PLR (baseline level), after PLR, immediately after VE were examined by echocardiography, and the central venous pressure (CVP) was monitored. The patients with increase in SV after VE (ΔSV) ≥ 15% were served as reaction group, while ΔSV < 15% were served as non-reaction group. The changes in LVEDV, LVESV, SV, LVEF and CVP at baseline level, after PLR and after VE were compared between the two groups. Pearson correlation method was used to analyze the correlation between ΔSV, increase in LVEF (ΔLVEF) after PLR and ΔSV, and ΔLVEF after VE. Receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of ΔSV and ΔLVEF after PLR for volume responsiveness. PLR and VE were successfully performed in 30 patients, of which 23 patients (76.7%) were enrolled in the reaction group, and 7 patients (23.3%) in the non-reaction group. Compared with baseline levels, LVEDV, SV, and LVEF in the reaction group were significantly increased after PLR [LVEDV (mL): 83.5±9.6 vs. 77.1±6.2, SV (mL): 48.5±5.6 vs. 43.2±4.9, LVEF: 0.58±0.04 vs. 0.56±0.06, all P < 0.05], and CVP was significantly increased after VE [cmH2O (1 cmH2O = 0.098 kPa): 7.4±3.3 vs. 4.6±0.7, P < 0.01], however, there was no significant change in LVESV. In the non-reaction group, SV and LVEF were significantly increased after PLR as compared with those at baseline levels [SV (mL): 42.7±3.7 vs. 40.6±3.1, LVEF: 0.52±0.05 vs. 0.50±0.05, both P < 0.05], while LVEDV and CVP were significantly increased after VE as compared with those at baseline levels [LVEDV (mL): 84.4±4.1 vs. 80.6±5.9, CVP (cmH2O): 10.6±3.5 vs. 7.6±0.5, both P < 0.05], however, there was no significant change in LVESV. Pearson correlation analysis showed that ΔSV and ΔLVEF after PLR were positively correlated with ΔSV and ΔLVEF after VE (r1 = 0.86, r2 = 0.65, both P < 0.01). ROC curve analysis showed that the area under ROC curve (AUC) of PLR-induced ΔSV and ΔLVEF for predicting volume responsiveness was 0.85 and 0.66 respectively. When the cut-off value of ΔSV after PLR was 10.6%, the sensitivity was 78.2%, the specificity was 82.3%; when the cut-off value of ΔLVEF after PLR was 3.6%, the sensitivity was 78.2%, and the specificity was 73.2%. ΔSV and ΔLVEF measured by PLR combined with echocardiography can be used to evaluate the volume responsiveness in patients with septic shock and can guide fluid therapy.

Left ventricular remodelling and change in left ventricular global longitudinal strain after cardiac resynchronization therapy: prognostic implications.

Cardiac resynchronization therapy (CRT) can reduce left ventricular end-systolic volume (LVESV), and a decrease of ≥15% is defined as a response. CRT can also improve LV global longitudinal strain (GLS). Changes in LVESV and LV GLS are individually associated with outcome post-CRT. We investigated LVESV and LV GLS changes and prognostic implications of improvement in LVESV and/or LV GLS, compared with no improvement in either parameter. Baseline and 6-month echocardiograms were analysed from CRT recipients with heart failure. LV reverse remodelling was defined as a ≥15% reduction in LVESV at 6 months post-CRT. A ≥5% absolute improvement in LV GLS was defined as a change in LV GLS. A total of 1185 patients were included (mean age 65 ± 10 years, 73% male), and those with an improvement in LVESV and LV GLS (n = 131, 11.1%) had significantly lower mortality compared with other groups. On multivariable analysis, an improvement in both LVESV and LV GLS [hazard ratio (HR): 0.47; 95% confidence interval (CI): 0.31-0.71; P < 0.001] or an improvement in either LVESV or LV GLS (HR: 0.57; 95% CI: 0.47-0.71; P < 0.001) were independently associated with better prognosis, compared with no improvement in either parameter. Either a reduction in LVESV and/or an improvement in LV GLS at 6 months post-CRT are independently associated with improved long-term prognosis, compared with no change in both LVESV and LV GLS. This supports the use of LV GLS as a meaningful parameter in defining CRT response.

Sleep Apnea Evolution and Left Ventricular Recovery After Percutaneous Coronary Intervention for Myocardial Infarction.

Sleep apnea is often newly diagnosed in patients presenting with ST-segment elevation myocardial infarction (STEMI). We assessed longitudinal changes in apnea-hypopnea index (AHI) and sleep apnea phenotype after STEMI and determined its association with changes in the left ventricular ejection fraction (LVEF). A total of 101 eligible patients with STEMI underwent consecutive sleep studies and echocardiographic studies within 5 days of admission and at 6-month follow-up. Sleep apnea (AHI ≥ 15 events/h) was further divided into obstructive sleep apnea (OSA) or central sleep apnea (CSA). Both AHI (mean difference -6.4 events/h, 95% confidence interval [CI] -9.6 to 3.3, P < .001) and LVEF (mean difference 2.6%, 95% CI 1.3 to 4.0, P < .001) improved from baseline to 6 months. The improvement in AHI was associated with an increase in LVEF (β = -.47, 95% CI -.86 to -.07, P = .023) and a decrease in left ventricular end-systolic volume (LVESV) (β = .25, 95% CI .07 to .43, P = .007). Of the patients with OSA at baseline (46%), resolution of OSA was seen in 48% at 6 months. Of those with CSA at baseline (12%), conversion to OSA was seen in 83%. In contrast, among those with no sleep apnea (42%) at baseline, the diagnosis remained the same in 93% at 6 months. Concurrent changes in AHI, LVEF, and LVESV were seen after STEMI. Sleep studies performed on admission are reliable in excluding sleep apnea. However, patients with OSA or CSA on admission warrant re-evaluation due to evolution of the sleep apnea phenotype.

Взаимосвязь уровня половых гормонов у мужчин с ответом на сердечную ресинхронизирующую терапию

To study the relationship between levels of sex hormones and effectiveness of cardiac resynchronisation therapy (CRT) in men with chronic heart failure (CHF). The best response to CRT (mean time, 38 [19,0;53,7] months) was identifed by a maximum decrease in left ventricular end-systolic volume (LVESV) in 58 men (mean age, 54.8±9.6) with CHF (61% IHD). Based on testosterone (TES) level, patients were divided into group 1 (n=28; 48%) - TES < median value (13.8 nmol/l) and group 2 (n=30; 52%) - TES > median value. Exercise tolerance (ET), echocardiography (EchoCG) parameters, plasma levels of NTproBNP, interleukin (IL) - 1β, IL-6, IL-10, tumor necrosis factor α (TNF-α), С-reactive peptide (CRP), galectin-3 (Gal-3), matrix metalloprotease-9 (ММР-9), tissue inhibitors of metalloproteinases TIMP-1, TIMP-4, and the indexes MMP-9/TIMP-1 and MMP-9/TIMP-4 were evaluated in dynamics. Levels of TES, progesterone (PGN), dehydroepiandrosterone sulphate (DHEAS), and estradiol (Е2) were measured at baseline. Based on LVESV changes, non-responders (LVESV decrease by 15% but 30%) were identifed. In group 2, atrial fibrillation (р=0.064) and radiofrequency ablation of atrioventricular connection (р=0.014) were observed more frequently; incidence of diabetes mellitus was lower (р=0.017); QRS was smaller (р=0.001); ET was higher both at baseline (р=0.022) and in dynamics (р=0.018); numbers of responders and super-responders were greater (р=0.007); levels of PGN (р=0.028), Il-1β (р=0.020), IL-10 (р=0.013), TNF- α (р=0.006) were higher; and Е2/TES was lower (р=0.004). While EchoCG parameters did not differ at baseline, group 2 showed a tendency towards greater changes in LVESV (р=0.069) and LV end systolic dimension (р=0.087), and a greater increase in LV ejection fraction (р=0.007). In dynamics: In group 1, a decrease in NT-proBNP was observed (р=0.015); in group 2, decreases in IL-1β (р=0.001), IL-6 (р=0.015), IL-10 (р=0.001), TNF-α (р=0.001), TIMP-1 (р=0.046), and Gal-3 (р=0.051) were observed. Levels of sex hormones were correlated with EchoCG parameters, biomarkers of immune inflammation, fibrosis, and NTproBNP. The ROC analysis showed that a TES level not lower than 13.8 nmol/l was a predictor for a positive response to CRT with a sensitivity of 63.4% and specifcity of 76.5% (AUC=0.687; р=0.026). High levels of TES and PGN were associated with beter effectivity of CRT, higher ET, greater proportions of responders and super-responders, and reduced immune inflammation activity and fibrosis. A level of TES not lower than 13.8 nmol/l was a predictor for a positive response to CRT.

Comparison of strain parameters in dyssynchronous heart failure between speckle tracking echocardiography vendor systems

BackgroundAlthough mechanical dyssynchrony parameters derived by speckle tracking echocardiography (STE) may predict response to cardiac resynchronization therapy (CRT), comparability of parameters derived with different STE vendors is unknown.MethodsIn the MARC study, echocardiographic images of heart failure patients obtained before CRT implantation were prospectively analysed with vendor specific STE software (GE EchoPac and Philips QLAB) and vendor-independent software (TomTec 2DCPA). Response was defined as change in left ventricular (LV) end-systolic volume between examination before and six-months after CRT implantation. Basic longitudinal strain and mechanical dyssynchrony parameters (septal to lateral wall delay (SL-delay), septal systolic rebound stretch (SRSsept), and systolic stretch index (SSI)) were obtained from either separate septal and lateral walls, or total LV apical four chamber. Septal strain patterns were categorized in three types. The coefficient of variation and intra-class correlation coefficient (ICC) were analysed. Dyssynchrony parameters were associated with CRT response using univariate regression analysis and C-statistics.ResultsTwo-hundred eleven patients were analysed. GE-cohort (n = 123): age 68 years (interquartile range (IQR): 61–73), 67% male, QRS-duration 177 ms (IQR: 160–192), LV ejection fraction: 26 ± 7%. Philips-cohort (n = 88): age 67 years (IQR: 59–74), 60% male, QRS-duration: 179 ms (IQR: 166–193), LV ejection fraction: 27 ± 8. LV derived peak strain was comparable in the GE- (GE: -7.3 ± 3.1%, TomTec: −6.4 ± 2.8%, ICC: 0.723) and Philips-cohort (Philips: −7.7 ± 2.7%, TomTec: −7.7 ± 3.3%, ICC: 0.749). SL-delay showed low ICC values (GE vs. TomTec: 0.078 and Philips vs. TomTec: 0.025). ICC’s of SRSsept and SSI were higher but only weak (GE vs. TomTec: SRSsept: 0.470, SSI: 0.467) (Philips vs. QLAB: SRSsept: 0.419, SSI: 0.421). Comparability of septal strain patterns was low (Cohen’s kappa, GE vs. TomTec: 0.221 and Philips vs. TomTec: 0.279). Septal strain patterns, SRSsept and SSI were associated with changes in LV end-systolic volume for all vendors. SRSsept and SSI had relative varying C-statistic values (range: 0.530–0.705) and different cut-off values between vendors.ConclusionsAlthough global longitudinal strain analysis showed fair comparability, assessment of dyssynchrony parameters was vendor specific and not applicable outside the context of the implemented platform. While the standardization taskforce took an important step for global peak strain, further standardization of STE is still warranted.

Impact of Left Ventricular vs Biventricular Pacing on Reverse Remodelling: Insights From the Evaluation of Resynchronization Therapy for Heart Failure (EARTH) Trial

BackgroundStudies comparing biventricular (BiV) cardiac resynchronization therapy (CRT) and left ventricular (LV) pacing alone have yielded conflicting results. We recently reported the results of the Greater Evaluation of Resynchronization Therapy for Heart Failure (GREATER-EARTH) trial demonstrating similar clinical benefits of BiV and LV-CRT on exercise tolerance. We report the prespecified secondary outcomes of the GREATER-EARTH trial, comparing the impact of BiV vs LV-CRT on structural and biochemical cardiac remodelling. MethodsPatients with a LV ejection fraction (LVEF) ≤ 35% and a QRS duration ≥ 120 ms were randomized to BiV-CRT or LV-CRT for a 6-month period, followed by crossover. The primary end point was a change in LV end-systolic volume (LVESV). Secondary end points included changes in LVEF, right ventricular (RV) dimensions and function, mitral regurgitation (MR), indices of diastolic function, systolic pulmonary artery pressure (sPAP), and disease-specific biomarkers. ResultsOne hundred twenty patients (60.9 ± 8.8 years; 75.0% men; LVEF, 24.4% ± 6.3%) were enrolled. A similar reduction in LVESV was observed, from a baseline of 162.4 ± 57.2 mL to 130.4 ± 63.4 mL with BiV pacing and 130.3 ± 59.9 mL with LV pacing (P = 0.679, BiV pacing vs LV pacing). Improvements in LVEF, RV remodelling, and N-terminal pro b-type natriuretic peptide were similar between groups. BiV pacing yielded superior outcomes with respect to LV diastolic function, indexed left atrial volume, degree of MR, and sPAP (all P < 0.05), together with decreased N-terminal propeptide of type III collagen with LV-CRT. ConclusionsIn this randomized double-blind crossover trial, BiV and LV pacing resulted in similar improvements in the primary LV remodelling end point (LVESV). Analyses of secondary end points revealed advantages of BiV pacing over LV pacing on several other features of cardiac remodelling, providing mechanistic insights to support the main finding of the GREATER-EARTH trial.

Effect of High Thoracic Sympathetic Nerve Block on Serum Collagen Biomarkers in Patients with Chronic Heart Failure

Objectives: The impact of high thoracic sympathetic block (HTSB) on myocardial fibrosis in chronic heart failure (HF) is unclear. Myocardial collagen synthesis can be assessed by measuring circulating biomarkers. We observed the effect of HTSB on serum collagen biomarkers in HF. Methods: Forty-four patients were randomized to a control and a HTSB group. They received routine medications. Repeated epidural injections were given to the HTSB group for 4 weeks. Echocardiography and measurements of serum carboxy-terminal propeptide of procollagen type I (PICP) and amino-terminal propeptide of procollagen type III (PIIINP) were performed at baseline and 4 weeks later. Results: There were significant reductions in left atrial diameter, left ventricular (LV) diameter and volume, LV weight index (LVWI) and serum PICP and PIIINP levels in the HTSB group (p < 0.05). The changes in LV end-systolic volume and ejection fraction (LVEF) were greater in the HTSB group than in the control group (p < 0.05). In the HTSB group, the decreases in PICP and PIIINP were correlated with the decrease in LVWI (PICP: r = 0.695, p = 0.000; PIIINP: r = 0.642, p = 0.001), and the decrease in PICP was negatively associated with the rise in LVEF (r = -0.813, p = 0.000). Conclusion: HTSB reduces myocardial fibrosis in HF, which may accompany the improvement of LV hypertrophy and dysfunction.