Increase In LVEF Research Articles

Modulation of p300 acetylation to protect against doxorubicin-induced cardiotoxicity

Abstract Background Doxorubicin (DOX) is a widely-used anti-neoplastic agent, but the most common adverse reaction to its use is cardiotoxicity(1). DOX acts by producing reactive oxygen species (ROSs) that cause DNA damage(1,2), which activates various proteins, including the tumour suppressor p53 and the acetyltransferase p300. When activated, p300 acetylates and increases the activity of p53 which leads to increased apoptotic activity(3). Cardiotoxicity results because the heart has limited mechanisms to dispose of ROSs(4), and because cardiomyocytes have a low turnover rate(5). Purpose We examined the p300 inhibitor Theracurmin (THR)(6,7) as a candidate to prevent DOX cardiotoxicity using an in-vivo mouse model, and sought to elucidate the underlying molecular mechanisms using in-vitro studies. Methods C57BL/6 mice were pre-treated with THR or vehicle (as control), then administered DOX or vehicle. Cardiac function was evaluated by echocardiography and cardiac catheterization. In vitro studies used cardiac fibroblasts (FBs) and cardiac endothelial cells (ECs) pre-treated with THR, then with DOX, as in the animal studies. Western blotting and rt-qPCR was used to quantify protein and mRNA levels of genes in the p53-p300 pathway or related to apoptosis, oxidative stress, and cell cycle control. Results DOX-treated mice showed significant decreases in left ventricular (LV) ejection fraction (LVEF, p=0.0004), fractional shortening (FS, p=0.0012), and a significant increase in end-systolic volume (ESV, p=0.0004). We also showed a significant decrease in anterior (LVAW;d, p=0.005) and posterior (LVPW;d, p=0.005) wall thickness of the LV in these mice. However, when mice were pre-treated with THR prior to DOX administration, we saw significant increases in LVEF (p=0.045) and LVPW;d (p=0.015), and a significant decrease in ESV (p=0.0047) compared to those that were not pre-treated. In-vitro analyses demonstrated a significant increase in cleaved caspase 3 protein expression in DOX-treated ECs (p=0.007), that was not prevented by THR pre-treatment. In DOX-treated FBs, we saw a reduction in AKT mRNA (p=0.017) and increases in BAX 9p=0.008), P21 (p=0.0001), and GADD45 (0.037) mRNA expression. In DOX-treated ECs, we also saw significant increases in BAX (p=0.015) and P21 (p=0.011) mRNA expression. These changes in mRNA expression were not reversed with THR pre-treatment in either cell type. Conclusion THR pre-treatment successfully mitigated functional deficits and structural deficits associated with DOX cardiotoxicity. In-vitro studies show that THR pre-treatment was not sufficient to significantly prevent changes in key molecular targets associated with apoptosis. Further studies are required to elucidate the mechanism behind the observed functional changes.Abstract OverviewAbstract Results

Effect of Hyperketonemia on Myocardial Function in Patients with Heart Failure and Type 2 Diabetes.

We examined the effect of increased plasma ketones on left ventricular (LV) function, myocardial glucose uptake (MGU), and myocardial blood flow (MBF) in type 2 diabetes (T2DM) patients with heart failure (HF). Three groups (I,II,III) of T2DM (12 per group) with LV ejection fraction ≤50% received incremental infusions of β-OH-B for 3-6 hours to raise plasma β-OH-B concentration throughout the physiologic (Groups I and II) and pharmacologic (Group III) range. Cardiac MRI was performed at baseline and after each β-OH-B infusion to provide measures of cardiac function. On a separate day, Group II also received NaHCO3 infusion, thus serving as their own control for time, volume, and pH. Additionally, Group II underwent positron emission tomography study with 18F-fluoro-2-deoxyglucose to examine effect of hyperketonemia on MGU. Groups I, II, III achieved plasma β-OH-B levels of 0.7±0.3, 1.6±0.2, 3.2±0.2 mmol/L, respectively. Cardiac output, LVEF, and stroke volume increased significantly during β-OH-B infusion in Groups II (CO, 4.54 to 5.30; EF, 39.9 to 43.8; SV, 70.3 to 80.0) and III (CO, 5.93 to 7.16; EF, 41.1 to 47.5; SV, 89.0 to 108.4) and did not change with NaHCO3 infusion in Group II. The increase in LVEF was greatest in Group III (p<0.001 vs Group II). MGU and MBF were not altered by β-OH-B. In T2DM patients with LVEF≤50%, increased plasma β-OH-B significantly increased LV function dose-dependently. Since MGU did not change, the myocardial benefit of β-OH-B resulted from providing an additional fuel for the heart without inhibiting MGU.

Efficacy, Safety and Mechanistic Impact of a Heart Failure Guideline-Directed Medical Therapy Clinic

BackgroundAlthough clinical evidence supports rapid institution of guideline-directed medical therapy (GDMT) for heart failure (HF), in actual practice, there remain large gaps in adherence to guideline recommendations. Recent data support safety and efficacy of rapid GDMT implementation; however, rapid GDMT deployment within a general cardiology environment remains unexplored. ObjectivesThe purpose of this study was to evaluate the efficacy and safety of a GDMT clinic within a general cardiology practice relative to usual care, the impact on prescription of GDMT, HF symptoms, N-terminal pro–B-type natriuretic peptide concentrations and echocardiographic parameters of remodeling. MethodsIndividuals with HF with an abnormal ejection fraction (<50%) referred to the GDMT clinic underwent rapid GDMT titration with close monitoring of clinical data. Rates of GDMT prescription were compared with a matched reference group. Patients underwent echocardiography at baseline and after GDMT clinic completion. ResultsA total of 114 persons were treated in GDMT clinic. The mean age was 67.6 ± 14.6 years, and 32 (28%) were women. Among those referred, 100 (87.7%) had no contraindications for 4-drug GDMT. From baseline to clinic completion (median 15.8 weeks [Q1-Q3: 10.7-23.0 weeks]), patients without medication contraindications experienced significant increases in 4-drug GDMT use (from 21% to 88%; P < 0.001); of 4-drug GDMT recipients, 92% received angiotensin receptor neprilysin inhibitor. GDMT clinic participants achieved higher medication doses than those in usual care, with greater achievement of ≥50% target dose of angiotensin receptor neprilysin inhibitor (52% vs 8%), beta-blocker (78% vs 6.2%), mineralocorticoid receptor antagonist (98% vs 15.6%), and sodium-glucose cotransporter 2 inhibitors (92% vs 6.2%). Target doses of all 4 drugs were reached in nearly 1 in 4 participants. HF symptoms improved (94% to 75% NYHA functional class II/III; P < 0.001) and N-terminal pro–B-type natriuretic peptide concentration decreased (median 587 to 534 ng/L; P = 0.03) despite loop diuretic reduction. Additionally, we observed an absolute 6% LVEF increase (from 37% [Q1-Q3: 31%-41%] to 43% [Q1-Q3: 38%-53%]; P < 0.001) and substantial decrease in moderate or severe mitral regurgitation. GDMT titration was well-tolerated. ConclusionsRapid GDMT implementation via an outpatient GDMT clinic was effective, safe, and associated with improvement in key clinical parameters. The more widespread role of GDMT clinics to improve HF care warrants further study.

Cost-Effectiveness Ratio Analysis of LBBaP Versus BVP in Heart Failure Patients With LBBB.

For the initial treatment strategy for patients with cardiac resynchronization therapy (CRT) indications, whether to choose left bundle branch area pacing (LBBaP) or biventricular pacing (BVP) remains controversial. We aimed to investigate the cost-effectiveness ratio (CER) of LBBaP and BVP in heart failure (HF) patients with left bundle branch block (LBBB). This observational study included HF patients with LBBB who underwent successful LBBaP or BVP. The primary outcomes were echocardiographic response (left ventricular ejection fraction [LVEF] increase ≥5%), LVEF improvement, hospitalization costs, and CER (CER = cost/echocardiographic response rate). Secondary outcomes included other echocardiographic parameters, New York Heart Association (NYHA), N-terminal pro-B-type natriuretic peptide (NT-proBNP), pacemaker parameters, complications, ventricular arrhythmia (VA) events, HF hospitalization (HFH), and all-cause mortality. A total of 130 patients (85 LBBaP and 45 BVP) were included (65.6 ± 10.0 years, 70.77% men). The median follow-up period was 16(12,30), months. Compared with BVP, the LBBaP group showed a greater increase in LVEF (20.2%±11.8% vs. 10.5%±13.9%; p<0.001), higher echocardiographic response rate (86.1% vs. 57.8%; p<0.001), and lower hospitalization costs [$9707.7 (7751.2, 18,088.5) vs. $20,046.1 (18,840.1, 22,447.3); p<0.0001]. The CER was 112.7 and 346.8 in LBBaP and BVP, respectively. The incremental cost-effectiveness ratio (ICER = △cost/△echocardiographic response rate) was $-365.3/per 1% increase in effectiveness. LBBaP improved cardiac function more significantly than BVP. There were no significant differences in clinical outcomes. LBBaP-CRT is more cost-effective than BVP, offering greater LVEF improvement, higher echocardiographic response rates, lower hospitalization costs, and more significantly improved cardiac function. These findings need large randomized clinical trials for further confirmation.

Difference in Cardiac Response after Transcatheter Aortic Valve Implantation according to Flow and Gradient Pattern.

In patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS), data on the differences in subsequent cardiac structure and function among stratified groups with flow gradient patterns through the aortic valve are insufficient. In this large multicenter study, 4,523 patients undergoing TAVI for severe AS between 2013 and 2019 were divided into 3 groups according to the following criteria: (1) high-gradient AS (HG-AS) (mean pressure gradient [MPG] ≥40 mmHg), (2) classical low-flow low-gradient AS (cLFLG-AS) (MPG <40 mmHg, left ventricular [LV] ejection fraction [LVEF] <50%), and (3) paradoxical low-flow low-gradient AS (pLFLG-AS) (MPG <40 mmHg, LVEF ≥50% but stroke volume index [SVi] <35 mL/m2). Echocardiography was performed at baseline, post-procedure, and 1 year post-TAVI. 3,697, 507, and 319 patients had HG-AS, cLFLG-AS, and pLFLG-AS, respectively. After adjusting for clinical factors, cLFLG-AS and pLFLG-AS had an approximately 1.5-fold higher 2-year all-cause mortality compared with HG-AS. During 1 year following TAVI, compared with HG-AS, cLFLG-AS showed greater reduction of LV systolic diameter (LVDs) and LV diastolic diameter (LVDd) and greater increase of LVEF (p<0.001 for all), and changes in LV mass index (LVMi) and SVi were comparable (p=0.915 and p=0.821, respectively). However, pLFLG-AS demonstrated less reduction of LVDs and LVDd (p=0.039 and p=0.001, respectively), less improvement of LVEF and LVMi (p=0.045 and p<0.001, respectively), and comparable change in SVi (p=0.364). During 1 year post-TAVI, compared with HG-AS, cLFLG-AS achieves smaller LV diameters, greater increase in LVEF, and comparable regression of LVMi, whereas pLFLG-AS does not.

Harmonizing Heartbeats: The Mosaic of Cardiac Resynchronization Therapy Responders-A Comprehensive Exploration of Diverse Criteria and Predictors.

Background: Heart failure (HF) remains a challenging healthcare issue necessitating innovative therapies like cardiac resynchronization-defibrillation therapy (CRT-D). However, the definition of a CRT-D response lacks uniformity, impeding effective clinical evaluation. This study explores diverse CRT-D responder definitions encompassing functional, echocardiographic and laboratory criteria. Materials & Methods: A single-center study involving 132 CRT-D patients scrutinized responder criteria including NYHA stage, LVEF increase and proBNP decrease. Statistical analyses such as Kaplan-Meier curves and Cox hazard regression were employed to evaluate responder characteristics and survival outcomes. Results: Responder rates varied across criteria, revealing nuanced patient profiles. CRT-D responders defined by NYHA decrease, LVEF increase or proBNP decrease exhibit improved survival rates after 2 and 3 years (p < 0.050). Young age, absence of recent myocardial infarction and normal right ventricular echocardiographic parameters emerge as predictors for positive response. In part, drug-based HF therapy correlates with increased responder rates. Cox regression identified LVEF ≥ 5% and proBNP decrease ≥ 25% as independent predictors of extended survival. Conclusions: CRT-D responder definitions exhibit considerable variability, emphasizing the need for a nuanced patient-centered approach. Factors like right ventricular function, drug therapy, atrial fibrillation and renal function influence responses. This study enriches our understanding of CRT-D response and contributes to the foundation for personalized HF management.

The effectiveness of cardiac contractility modulation: results of two-year follow-up

Aim. To evaluate the survival and dynamics of clinical and instrumental data in patients with chronic heart failure (CHF), atrial fibrillation (AF) and cardiac contractility modulation (CCM).Methods. There were included 54 patients (40 men, median age 59.7 [56.6; 63.9] years) with signs of CHF II (n=27, 50%) functional class and III (n=27, 50%) NYHA functional class, significantly decreased left ventricular ejection fraction (LVEF=30 [24,7; 35,5]%), LV dilatation and paroxysmal (n=27, 50%) or permanent (n=27, 50%) AF. In all patients, devices for CCM were implanted. The dynamics of clinical and instrumental parameters were assessed in 2, 6, 12 and 24 months after implantation. The actual survival patients with CCM was compared with the predicted survival calculated using the Seattle model of heart failure and MAGGIC risk score.Results. In 14 (28%) of patients CCM resulted in significantly increased clinical, echocardiographic parameters (increase in LVEF by 15 [11; 20]%, decrease in end-systolic volume by 68,5[37.5;104.5] ml and end-diastolic volume by 44 [30,100] мл), increase in walking distance during 6-minute walking test and decrease of NT-proBNP. The only factor significant for maximal response was non-ischemic etiology of CHF (χ2=4.54, p=0.034). During 2 years 21 (42%) patients died. The all-cause mortality in patients with CCM to the first year of observation was 16%, two-year all-cause mortality - 40%. These figures turned out to be significantly higher than predicted according to the Seattle model (χ2=10.93, p=0.001). The predicted and actual risk of death at 12-month follow-up turned out to be comparable when assessing survival parameters according to the MAGGIC scale. (χ2=2.24, p=0.134).Conclusion. CCM therapy in some patients with CHF of non-ischemic etiology can lead to an improvement of all clinical and instrumental characteristics. At the same time, there is no effect of CCM on the prognosis of patients with CHF. This fact may suggest the need of additional studies with increased number of cases.

Leadless ultrasound-based cardiac resynchronization system in heart failure results from the SOLVE-CRT randomised sub-study and the primary population patient cohort

Abstract Background Despite the well-established role of CRT in heart failure, major limitations of CRT include an occasional incidence of unsuccessful coronary sinus (CS) lead placement, one third non-responders in conventional CRT patients and higher complications risk in CRT upgrade procedures. The WiSE® CRT System (EBR Systems, Inc) is designed to overcome these limitations. Prior non-randomized studies with the WiSE System have shown high implant success rates and improvement in LV remodeling and heart failure symptoms. Objectives The pivotal SOLVE-CRT study is comprised of two parts: a randomized part and the subsequent single-arm part enrolled during the pandemic. The primary safety endpoint is freedom from Type I (device &amp; procedure-related) complications through 6 months and primary efficacy endpoint is the mean relative (%) change in left ventricular end systolic volume (LVESV) from baseline to 6 months. Method Between Jan. 2018 and Mar. 2020 the randomized part enrolled 108 participants for three indications: non-responders (NR), previously untreated, including acute and chronic lead failures (PU), and high-risk upgrades (HRU). All underwent device implantation and were then randomized in 1:1 ratio to Treatment (system turned ON) or Control (system turned OFF) groups. In the single arm, 75 participants had been enrolled within two indications: PU and HRU. The efficacy analysis of the entire randomised cohort included 99 participants (PU, HRU, NR). For the primary indication sub-population, 57 participants (PU, HRU) were analysed. Results Randomized Group: Results were available for 91 of the 99 patients. Significant improvements were seen between the Treatment and Control groups with a mean reduction in LVESV (-14.6% vs -5.2%, p=0.005), mean reduction in LVEDV (-8.1% vs -3.0%, p=0.027), mean increase in LVEF (5.4% vs 2.4%, p=0.048) and mean reduction in QRS (-41.9ms vs -1.7ms, p=0.001). Primary Indication Sub-Population Group: The primary indication sub-population also saw significant improvements between Treatment and Control group with a mean reduction in LVESV (-18.2% vs -3.1%, p=0.002), mean reduction in LVEDV (-11.6% vs -2.1%, p=0.004), mean increase in LVEF (5.7% vs 1.1%, p=0.025) and mean reduction in QRS (-38.0ms vs -3.1ms, p&amp;lt;0.001). Conclusion This pivotal SOLVE-CRT trial demonstrates that leadless, ultrasound-based endocardial pacing for heart failure is feasible and efficacious showing evidence of left ventricular remodelling and electrical response after 6 month in the primary population as well as in the sub-study group. Picture 1: Efficacy entire randomised population Picture 2: Efficacy primary indications population

Deep septal pacing for pacemaker-induced cardiomyopathy

Abstract Background Conventional right ventricular pacing can impair left ventricular function and cause heart failure, known as pacing induced cardiomyopathy (PICM). Upgrade to cardiac resynchronization therapy (CRT) is the most common treatment for PICM. Recently, left bundle branch area pacing (LBBAP) has emerged as a potential alternative both to conventional RV pacing and to CRT. In Deep septal pacing (DSP), a simplified alternative to LBBAP, the lead is inserted deep in the septum, does not reach the subendocardial area, but is still able to achieve narrower paced QRS than during conventional pacing. Purpose The aim of this study was to assess the effect of DSP in a cohort of patients with PICM. Methods We included consecutive patients diagnosed with PICM who were referred to our unit between January 2020 and January 2022 for a device upgrade. The aim was to upgrade patients to DSP. In the absence of terminal R wave in V1, the procedure was considered successful if a paced QRS duration ≤140 ms was obtained. Clinical and device follow-up were performed one and 6 months after the procedure, and echocardiography at 6 months. The study was approved by the Clinical Research Ethics Committee and all patients signed informed consent. Results Fifteen patients were recruited during the study period. One patient was excluded because a QRS ≤ 140 ms could not be achieved, and 2 other patients because a terminal R wave in paced QRS in V1 was obtained. The characteristics of the 12 included cases are detailed in Table 1. The mean LVEF was 33% (SD 4%) and the mean percentage of RV pacing was 99% (SD 1%). All patients had symptomatic heart failure. Non stylet-driven electrodes were used in 8 of the 12 patients. Acute threshold was &amp;lt; 1V - 0’4 ms in all, and remained stable during follow-up. No procedure-related complications or lead dislodgements were detected. The mean paced QRS duration with RV pacing was 172 ms (SD 14 ms) whereas after the upgrade it was 130 ms (SD 7 ms). As compared to RV pacing, DSP was associated with a significant reduction in paced QRS duration (mean difference 41 ms, p&amp;lt;0.001). As shown in Table 1, after DSP all patients except one (11/12, 92%) experienced an increase in LVEF of at least 10%; five patients (42%) achieved an LVEF&amp;gt;50%. The mean LVEF after the upgrade was 46% (SD 9%). The mean improvement in LVEF with DSP was 13% (SD 10%). Conclusions In patients with PICM, deep septal pacing achieves narrower QRS as compared to RV pacing and is associated with a significant improvement in LVEF. Deep septal pacing might be an effective and simpler alternative to biventricular or left bundle branch pacing in patients with PICM.Table 1

Impact of non-typical LBBB on CRT response

Abstract Introduction Cardiac resynchronization therapy (CRT) benefits have been established in patients with heart failure and reduced left ventricular ejection fraction (HFrEF) who have a broad QRS and remain symptomatic despite optimized medical therapy. Responders typically are female, with LBBB and broader QRS. It remains uncertain to what extent do patients with non-LBBB QRS complex morphology respond to CRT and also if there are differences among various types of intraventricular conduction delays. Purpose To evaluate the impact of non-typical left bundle branch block (LBBB) on reverser remodeling and clinical events. Methods Single center, observational, retrospective study including patients (pts) who implanted CRT in the context of HFrEF, from 2015 to 2020. Evaluation of QRS morphology analysis was conducted. CRT response was defined by a reduction of LVESV≥15% or an increase in LVEF≥10%. Predictors of CRT response were evaluated with Chi-square and Mann- Whitney analysis. Impact on reverse remodeling and clinical outcomes was performed with Kaplan-Meyer analysis. Results A total of 361 pts were included for analysis, of which 184 had non-typical LBBB. Pts had a mean age of 71±9years old, the majority of pts were female (61%), and almost half were ischemic (47.8%). EGC evaluation prior to CRT implantation, revealed an atypical LBBB in 83 (45.1%) pts, typical RBBB in 23 (12.5%) pts, atypical RBBB 94.(9%) pts and nonspecific intraventricular conduction delay in 69 (37.5%) pts. During a mean time of follow-up of 2.9 ±2.4years, 33 pts (18%) had hospitalizations due to HF and 68 (37%) died. In this cohort, 78 pts (42.4%) were deemed as responders, who presented a better clinical outcome when compared to non-responders (p &amp;lt; 0.001, HR 2.629 [95% CI 1.635-4.225]. There was no difference among the four types of intraventricular conduction analyzed in respect to degree of CRT response – figure 1. Regarding clinical events during follow-up, there was once again no significant difference among the different patterns of non-typical LBBB– figure 2. In this subset population we found no independent predictors of CRT response, although non-responders were significantly older than responders (72±8 vs 69±10 years-old (p=0.016). Conclusion Although pts with non-typical LBBB morphology display a lower therapy response to CRT than reported for LBBB pts, the rate of response is not negligible and represents a protective factor for clinical outcomes. Different types of intraventricular conduction delay present no difference regarding long- term prognosis or reverse remodeling.Survival according to CRT response

Echocardiographic follow-up after AV node ablation combined with left bundle branch area pacing for patients with symptomatic atrial fibrillation

Abstract Background AV node ablation combined with permanent pacing is an established therapy for rate control in patients with symptomatic atrial fibrillation (AF) refractory or intolerant to pharmacological rate or rhythm control and not eligible for rhythm control by left atrial catheter ablation. The threshold for performing this so-called "pace-and-ablate" strategy has decreased since the introduction of conduction system pacing, and especially left bundle branch area pacing (LBBAP). Purpose To investigate the change of the left-ventricular (LV) ejection fraction (EF) and left-atrial volume index (LAVI) in patients with symptomatic AF, twelve months after LBBAP and AV-node ablation. Methods Consecutive patients with symptomatic AF intolerant or refractory to pharmacological rate and symptom control and deemed not eligible for left atrial catheter ablation were included. At baseline, the EHRA score was noted and the LVEF and LAVI were measured echocardiographically. Patients were subdivided in a normal baseline LV ejection fraction (LVEF &amp;gt;50%) or diminished baseline LVEF (LVEF &amp;lt;50%) group. After LBBAP, patients underwent AV node ablation in the same procedure or four weeks later. After twelve months, the LVEF and LAVI were reassessed in the entire cohort and the two subgroups. Results Twenty-two patients (68% female, mean age 79±4 years) scheduled for pace-and-ablate therapy were prospectively included. Three (14%) had paroxysmal, sixteen patients (72%) had persistent AF and three patients (14%) long-standing persistent AF. An EHRA class IIb or higher was found in eighteen patients (82%). At baseline, the mean LVEF was 51 ± 7%, the mean LVEDD 47 ± 6 mm and LAVI 54 ± 18 ml/m2. Twelve patients (55%) had a preserved LVEF, whereas ten patients (45%) had an LVEF &amp;lt;50%, fig. 1. After twelve months, the overall ejection fraction increased to 54 ± 5% (p=0.016), fig. 2A. This was mostly attributed to the increase in LVEF to 51 ± 5% in the subgroup with a reduced baseline LVEF (p=0.009 compared to baseline 44 ± 5%), fig. 2A. The LVEF was unaffected in the other group (57 ± 3% vs. 57 ± 4%, p=0.63), fig. 2A. The LAVI was not significantly reduced in the overall cohort or the subgroups (54 ± 18 ml/m2 to 51 ± 19 ml/m2, p=0.16), fig 2B. Conclusion AV node ablation combined with LBBAP results in a significant improvement in LVEF at twelve months follow-up. This is mainly driven by an improvement in LVEF in those patients with a diminished LVEF at baseline. The data suggests that the therapy can reverse a tachycardiomyopathy without inducing a pacing-induced cardiomyopathy. No significant reduction in LAVI was found.Baseline characteristicsChanges in LVEF (A) and LAVI (B)

Symptom-to-balloon time and risk of ventricular arrhythmias in patients with STEMI undergoing percutaneous coronary intervention: The VERY-STEMI study

BackgroundVentricular arrhythmias (VAs) mainly occur in the early post-myocardial infarction (MI) period. However, studies examining the association between total myocardial ischemia time interval and the risk of new-onset VAs during a long-term follow-up are scarce. MethodsThis study (symptom-to-balloon time and VEntricular aRrhYthmias in patients with STEMI, VERY-STEMI study) was a multicenter, observational cohort and real-world study, which included patients with ST-segment elevation MI (STEMI) undergoing percutaneous coronary intervention (PCI). The primary endpoint was cumulative new-onset VAs during follow-up. The secondary endpoints were the major adverse cardiovascular events (MACE) and changes in left ventricular ejection fraction (ΔLVEF, %). ResultsA total of 517 patients with STEMI were included and 236 primary endpoint events occurred. After multivariable adjustments, compared to patients with S2BT of 24 h-7d, those with S2BT ≤ 24 h and S2BT > 7d had a lower risk of primary endpoint. RCS showed an inverted U-shaped relationship between S2BT and the primary endpoint, with an S2BT of 68.4 h at the inflection point. Patients with S2BT ≤ 24 h were associated with a lower risk of MACE and a 4.44 increase in LVEF, while there was no significant difference in MACE and LVEF change between the S2BT > 7d group and S2BT of 24 h-7d group. ConclusionsS2BT of 24 h-7d in STEMI patients was associated with a higher risk of VAs during follow-up. There was an inverted U-shaped relationship between S2BT and VAs, with the highest risk at an S2BT of 68.4 h.

Dynamics of the left ventricular ejection fraction after revascularization in patients with heart failure with preserved ejection fraction, association with the TRAIL protein

Aim. To study the association of dynamics of the ejection fraction (EF) of the left ventricle (LV) with the development of adverse cardiovascular events within 12 months after revascularization in patients with chronic heart failure with preserved LV EF (HFpEF), and to determine the value of TNF-related apoptosis-inducing ligand (TRAIL) in predicting changes of LVEF. Materials and methods. 52 patients with HFpEF hospitalized for coronary artery bypass grafting (CABG) were included in the prospective study. The levels of plasma NTproBNP (before CABG) and TRAIL protein (before CABG and 10 days after CABG) were determined. Echocardiography was performed for these patients at the time of enrollment in the study and after 12 months of follow-up. The patients were divided into 2 groups: group 1 (n=23) included patients with increased LVEF, group 2 (n=29) – with unchanged or reduced LVEF. The development of a combined endpoint (cardiovascular death, decompensated of HF, repeat unplanned revascularization) was studied. Results. LVEF before CABG was comparable in the studied groups. The frequency of the combined endpoint was 0 in the first group and 17.2% in the second group (p=0.02). There was an inverse correlation between change of LVEF one year after revascularization and the dynamics of the TRAIL protein in the perioperative period (r=-0.45, p=0.049). The area under the ROC for perioperative TRAIL changes and changes in LVEF during a follow-up was 0.79 (95% confidence interval 0.6–0.985; p=0.018). Conclusion. The increase of LVEF 12 months after CABG in patients with HFpEF is associated with a rarer development of cardiovascular events. The changes of LVEF after CABG can be predicted based on the analysis of the perioperative changes of the TRAIL protein.

Long-term effects of enhanced external counterpulsation in the management of patients with coronary artery disease complicated by heart failure: data from the EXCEL study

Aim. To study the long-term effect of complex therapy with enhanced external counterpulsation (EECP) on exercise tolerance, quality of life, and systolic cardiac function in patients with stable coronary artery disease (CAD) complicated by heart failure (HF).Material and methods. Open randomized study EXCEL (NCT05913778) included 118 patients with verified stable CAD complicated by NYHA class II-III HF with reduced or mildly reduced ejection fraction (EF). The patients were randomized into group 1 (n=59) who received optimal therapy and EECP (35 hours, 2 courses per year) or group 2 (n=59), who recived optimal drug therapy and EECP (35 hours, 1 course per year). All patients underwent a 6-minute walk test (6MWT) at baseline, 12, 24 and 36 months, the assessment of clinical status, Minnesota Living with Heart Failure Questionnaire (MLHFQ), N-terminal pro-brain natriuretic peptide (NTproBNP) levels, LVEF and clinical outcomes.Results. In both groups, we revealed an improvement of HF class (average HF class after 36 months decreased in the 1st group from 2,40 to 1,86 (p&lt;0,001), and in the 2nd group from 2,37 to 2,17 (p&lt;0,001)) and clinical status of patients. A significant increase in 6MWT distance after 24 months was revealed in both groups — in group 1 by 59,4% (95% confidence interval (CI) 36,9-76,8), and in group 2 — by 34,3% (95% CI 26,7-40,1). The proportions of patients with an increase in 6MWD distance &gt;20% in groups 1 and 2 after 36 months were 100% (n=59) and 79,7% (n=47) (p&lt;0,001), respectively. There was a significant decrease in the MLHFQ score after 36 months in the 1st group by 43,8% (95% CI 40,5-47,1), and in the 2nd group by 30,0% (95% CI 26,4-33,6), NT-proBNP decrease, as well as an increase in LVEF. There were no deaths in group 1, while in group 2, mortality was 3,4%.Conclusion. A 36-month follow-up of patients with CAD complicated by HF receiving EECP revealed stable improvements in exercise tolerance, quality of life, systolic cardiac function, more pronounced in the group with 2 courses of EECP per year, as well as a decrease in the incidence of adverse outcomes.

Determinants and effects of microvascular obstruction on serial change in left ventricular diastolic function after reperfused acute myocardial infarction.

Although left ventricular (LV) diastolic dysfunction is more related to functional capacity after acute myocardial infarction (AMI), the determinants of LV diastolic functional change after reperfused AMI remain unknown. This study aimed to investigate the effects of microvascular obstruction (MVO) on mid-term changes in LV diastolic function after reperfused AMI. In a cohort of 72 AMI patients who underwent successful revascularization, echocardiography and cardiovascular magnetic resonance imaging were repeated at 9-month intervals. The late gadolinium enhancement (LGE) amount, segmental extracellular volume fraction, global LV, and left atrial (LA) phasic functions, along with mitral inflow and tissue Doppler measurements, were repeated. Among the included patients, 31 (43%) patients had MVO. During the 9-month interval, LV ejection fraction (EF) and LV global longitudinal strain (GLS) were significantly improved in accordance with a decrease in LGE amount (from 18.2 to 10.3 g, p < 0.001) and LV mass. The deceleration time (DT) of early mitral inflow (188.6 ms-226.3 ms, p < 0.001) and LV elastance index (Ed; 0.133 1/ml-0.127 1/ml, p = 0.049) were significantly improved, but not in conventional diastolic functional indexes. Their improvements occurred in both groups; however, the degree was less prominent in patients with MVO. The degree of decrease in LGE amount and increase in LVEF was significantly correlated with improvement in LV-Ed or LA phasic function, but not with conventional diastolic functional indexes. In patients with reperfused AMI, DT of early mitral inflow, phasic LA function, and LV-Ed were more sensitive diastolic functional indexes. The degree of their improvement was less prominent in patients with MVO.

Effect of empagliflozin on left ventricular volumes in type 2 diabetes or prediabetes heart failure patients with reduced ejection fraction

Objective Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as empagliflozin are antidiabetic drugs that have recently been reported to have cardio-protective action; however, their effect on cardiac structure and function in heart failure with reduced ejection fraction (HFrEF) has not yet been determined. This study evaluates the efficacy of empagliflozin on left ventricular (LV) volumes in type 2 diabetes or prediabetes patients with HFrEF. Methods This randomised, double-blind, trial study was conducted on 104 patients with type 2 diabetes or prediabetes with HFrEF referred to Imam Khomeini and Golestan hospitals in Ahvaz, Iran. The patients were randomised to receive empagliflozin (10 mg once daily) in addition to standard treatments of HFrEF or receive only standard treatments (control group) for six months. During the six months of follow-up, changes in LV volumes, LVEF, hospitalisation for heart failure (HF) were evaluated. Results Empagliflozin reduced LVEDVI and LVESVI by 10.0 and 8.0 mL/m2 (p < 0.0001). Furthermore, a significant increase in LVEF was observed in the empagliflozin group (p < 0.0001) without any significant change in the control group (p = 0.389). The hospitalisation rate was lower in the empagliflozin group than the control group (3.8% vs. 23.1%; p = 0.008). Conclusions Empagliflozin is effective in reducing LV volumes and hospitalisation rate in patients with type 2 diabetes and prediabetes and HFrEF. Therefore, treatment with empagliflozin for six months was associated with a significant reduction in adverse cardiovascular outcomes in these patients.

Myocardial analysis from routine 4D cardiac-CT to predict reverse remodeling and clinical outcomes after transcatheter aortic valve implantation

PurposeOur study aimed to determine whether 4D cardiac computed tomography (4DCCT) based quantitative myocardial analysis may improve risk stratification and can predict reverse remodeling (RRM) and mortality after transcatheter aortic valve implantation (TAVI). MethodsConsecutive patients undergoing clinically indicated 4DCCT prior to TAVI were prospectively enrolled. 4DCCT-derived left- (LV) and right ventricular (RV), and left atrial (LA) dimensions, mass, ejection fraction (EF) and myocardial strain were evaluated to predict RRM and survival. RRM was defined by either relative increase in LVEF by 5% or relative decline in LV end diastolic diameter (LVEDD) by 5% assessed by transthoracic echocardiography prior TAVI, at discharge, and at 12-month follow-up compared to baseline prior to TAVI. ResultsAmong 608 patients included in this study (55 % males, age 81 ± 6.6 years), RRM was observed in 279 (54 %) of 519 patients at discharge and in 218 (48 %) of 453 patients at 12-month echocardiography. While no CCT based measurements predicted RRM at discharge, CCT based LV mass index and LVEF independently predicted RRM at 12-month (ORadj = 1.012; 95 %CI:1.001–1.024; p = 0.046 and ORadj = 0.969; 95 %CI:0.943–0.996; p = 0.024, respectively). The most pronounced changes in LVEF and LVEDD were observed in patients with impaired LV function at baseline. In multivariable analysis age (HRadj = 1.037; 95 %CI:1.005–1.070; p = 0.022) and CCT-based LVEF (HRadj = 0.972; 95 %CI:0.945–0.999; p = 0.048) and LAEF (HRadj = 0.982; 95 %CI:0.968–0.996; p = 0.011) independently predicted survival. ConclusionComprehensive myocardial functional information derived from routine 4DCCT in patients with severe aortic stenosis undergoing TAVI could predict reverse remodeling and clinical outcomes at 12-month following TAVI.

Effects of balloon pulmonary valvuloplasty on longitudinal changes in right ventricular strain and strain rate in pediatric pulmonary stenosis.

Balloon Pulmonary Valvuloplasty (BPV) is a procedure for Pulmonary Stenosis (PS) treatment. In this study, right ventricle (RV) performance was determined through 2D-Speckle Tracking Echocardiography (2D-STE). The study involved 25 diagnosed children with PS undergoing BPV and 25 normal children. They were examined using 2D-STE and Linear Mixed Model (LMM) approach was used to determine changes in Pulmonary Valve Peak Gradient (PVPG), Tricuspid Annular Plane Systolic Excursion (TAPSE), strain and Strain Rate (SR) for RV, and Ejection Fraction for Left Ventricle (LVEF). Notable differences were found between two groups in TAPSE (P=0.001), global strain (P=0.001), apical septal strain (P=0.024), middle septal strain (P=0.001), basal septal strain (P=0.001), apical lateral SR (P=0.001), middle lateral SR (P=0.007), basal lateral SR (P=0.001), and apical septal SR (P=0.001). Post-BPV, there was an increase in LVEF (P=0.001) and TAPSE (P=0.001) but PVPG decreased (P=0.001). Following BPV, an increase was observed in apical lateral strain (P=0.004), middle septal strain (P=0.001), apical septal strain (P=0.003), middle septal strain (P=0.001), basal septal strain (P=0.048), apical septal SR (P=0.025), and middle septal SR (P=0.023). Gender was remarkably correlated with mean changes in basal lateral strain (P=0.019), middle septal strain (P=0.037), and middle septal SR (P=0.020). Age of PS children was related to mean change in basal septal strain (P=0.031) and basal septal SR (P=0.018). Strain and SR in RV improved post-BPV in children with PS. The gender and age of the children revealed remarkable effects on RV strain and SR changes after BPV.

Long-term outcomes and reverse remodelling in recently diagnosed unexplained left ventricular systolic dysfunction.

In patients with recently diagnosed non-ischaemic LV systolic dysfunction, left ventricular reverse remodelling (LVRR) and favourable prognosis has been documented in studies with short-term follow-up. The aim of our study was to assess the long-term clinical course and stability of LVRR in these patients. We prospectively studied 133 patients (37 women; 55 [interquartile range 46, 61] years) with recently diagnosed unexplained LV systolic dysfunction, with heart failure symptoms lasting <6months and LV ejection fraction <40% persisting after at least 1week of therapy. All patients underwent endomyocardial biopsy (EMB) at the time of diagnosis and serial echocardiographic and clinical follow-up over 5years. LVRR was defined as the combined presence of (1) LVEF≥50% or increase in LVEF≥10% points and (2) decrease in LV end-diastolic diameter index (LVEDDi)≥10% or (3) LVEDDi≤33mm/m2. LVRR was observed in 46% patients at 1year, in 60% at 2years and 50% at 5years. Additionally, 2% of patients underwent heart transplantation and 12% experienced heart failure hospitalization. During 5-year follow-up, 23 (17%) of the study cohort died. In multivariate analysis, independent predictors of mortality were baseline right atrial size (OR 1.097, CI 1.007-1.196), logBNP level (OR 2.02, CI 1.14-3.56), and PR interval (OR 1.02, CI 1.006-1.035) (P<0.05 for all). The number of macrophages on EMB was associated with overall survival in univariate analysis only. LVRR at 1year of follow-up was associated with a lower rate of mortality and heart failure hospitalization (P=0.025). In multivariate analysis, independent predictors of LVRR were left ventricular end-diastolic volume index (OR 0.97, CI 0.946-0.988), LVEF (OR 0.89, CI 0.83-0.96), and diastolic blood pressure (OR 1.04, CI 1.01-1.08) (P<0.05 for all). LVRR occurs in over half of patients with recent onset unexplained LV systolic dysfunction during first 2years of optimally guided heart failure therapy and then remains relatively stable during 5-year follow-up. Normalization of adverse LV remodelling corresponds to a low rate of mortality and heart failure hospitalizations during long-term follow-up.

Delayed Trastuzumab-induced Cardiotoxicity Leading to Severe Left Ventricular Dysfunction.

An 81-year-old woman presented to our hospital with dyspnea. She had been treated with trastuzumab for nine years. Chest radiography revealed pleural effusion. Transthoracic echocardiography revealed dyskinesis of the interventricular septum (IVS). Cardiac magnetic resonance imaging revealed increased native T1 values at the interventricular septum and apex, indicating myocardial edema or fibrosis in these areas. A transthoracic echocardiogram after half a year revealed an increase in LVEF from 25% to 48%. Serial transthoracic echocardiography and cardiac magnetic resonance imaging were useful for evaluating the cardiac structure and function in the present case of delayed trastuzumab-induced myocardial injury.