Treatment Of Ischemic Heart Failure Research Articles

Ultrasound-targeted microbubble destruction rapidly improves left ventricular function in rats with ischemic cardiac dysfunction

BackgroundPrevious studies have demonstrated the efficacy of ultrasound-targeted microbubble destruction (UTMD) in the treatment of ischemic heart failure (HF). The purpose of this study was to explore the mechanism by which UTMD improves ischemic HF. MethodsAn ischemic heart failure model was established using Sprague-Dawley rats. Rats were randomly divided into 7 groups: sham group, HF group, HF + MB group, HF + ultrasound (US) group, HF + UTMD group, HF + UTMD+LY294002 group, and HF + LY294002 group. Serum BNP level and echocardiographic parameters were measured to evaluate cardiac function. PI3K/Akt/eNOS signaling pathway protein levels were detected by immunohistochemistry (IHC) and western blotting. The concentrations of nitrous oxide (NO) and ATP were detected by ELISA, and hematoxylin and eosin (HE) staining was used to evaluate myocardial tissue. ResultsUTMD rapidly improved ejection fraction (EF) (HF: 37.16 ± 1.21% vs. HF + UTMD: 46.31 ± 3.00%, P < 0.01) and fractional shortening (FS) (HF: 18.53 ± 0.58% vs. HF + UTMD: 24.05 ± 1.84%, P < 0.01) in rats with ischemic HF. UTMD activated the PI3K/AKT/eNOS signaling pathway (HF vs. HF + UTMD, P < 0.01) and promoted the release of NO and ATP (HF vs. HF + UTMD, both, P < 0.05). Inhibition of the PI3K/AKT/eNOS signaling pathway by LY294002 worsened EF (HF: 37.16 ± 1.21% vs. HF + LY294002: 32.73 ± 3.05%, P < 0.05), and the release of NO and ATP by UTMD (HF + UTMD vs. HF + UTMD+LY294002, P < 0.05). ConclusionsUTMD can rapidly improve cardiac function in ischemic HF by activating the PI3K/Akt/eNOS signaling pathway and promoting the release of NO and ATP.

A Personalized Cell-Based Therapy for Ischemic Heart Failure With Reduced Ejection Fraction: Safety and Feasibility Outcomes of the Roll-In Cohort of the CardiAMP Cell Therapy Trial and Review of Similar Trials.

CardiAMP Cell Therapy for Heart Failure trial is a prospective, multicenter, randomized, controlled, double-blinded trial that has been granted breakthrough designation by the United States Food and Drug Administration. This trial evaluates clinical outcomes of intramyocardial delivery of a high dose of autologous bone marrow mononuclear cells in chronic postmyocardial infarction heart failure patients. This trial represents the first attempt to personalize marrow-derived cell-based therapy for the treatment of ischemic heart failure with reduced ejection fraction. The roll-in cohort of 10 patients demonstrated improvements in 6-minute walk distance at 6 months (+47.8 m, P = 0.01), 12 months (+46.4 m, P = 0.06), and 24 months (+31 m), and improvements in New York Heart Association class at 3 months (P = 0.015) and 6 months (P = 0.037). Four patients were reduced to New York Heart Association class I at 24 months and Minnesota Living with Heart Failure Questionnaire score was improved in 6 of 10 patients at 24 months. The improved clinical outcomes demonstrated in CardiAMP are consistent with previous clinical trials including the Transendocardial Autologous Cells in Ischemic Heart Failure (TAC-HFT) trial, Prospective Randomized Trial of Direct Endomyocardial Implantation of Bone Marrow Cells for Treatment of Severe Coronary Artery Diseases (PROTECT-CAD), and REGENERATE-Ischemic Heart Disease trial.

Treatment of ischemic heart failure through ultrasound-targeted microbubble destruction and it's mechanism

Abstract Background The cavitation effect mediated by ultrasonic-targeted microbubble destruction (UTMD) can regulate the microenvironment and circulation of ischemic myocardium. The UTMD cavitation effect can rapidly enhance blood perfusion and improve cardiac function in patients with ischemic heart failure. However, the internal mechanism of this treatment has yet to be reported. Objective The objective of this study was to explore the underlying mechanism of UTMD-mediated cavitation effect to rapidly improve cardiac function in rats with ischemic heart failure. Methods In the first part of the study, the ischemic heart failure model was induced by ligation of the left anterior descending branch coronary in Sprague-Dawley rats, the rats were randomly divided into 7 groups: sham group, HF group, HF+MB(microbubble) group, HF+US(ultrasound) group, HF+UTMD group, HF+UTMD+LY294002(PI3K inhibitor) group, and HF+LY294002 group. Serum BNP level and echocardiographic parameters were measured to evaluate cardiac function. Thereafter, SD rats were treated with UTMD by specific ultrasonic parameters and microbubble concentration, cardiac function should be reassessed after treatment. Finally, the myocardial tissues were extracted for Western Blot and immunohistochemical analysis to detect the protein expression of the PI3K/Akt/eNOS signaling pathway, and the contents of serum nitric oxide(NO) and myocardial ATP were detected by Elisa. Results The application of UTMD resulted in significant improvements in ejection fraction (EF) and fractional shortening (FS) in rats with ischemic heart failure, as compared to the HF group (EF: 37.16 ± 1.21% vs. HF+UTMD: 46.31 ± 3.00%, P=0.0057; FS: 18.53 ± 0.58% vs. HF+UTMD: 24.05 ± 1.84%, P=0.0089). Additionally, UTMD treatment led to the activation of the PI3K/Akt/eNOS signaling pathway (HF vs. HF+UTMD, P &amp;lt; 0.01), and promoted the production of NO and ATP (HF vs. HF+UTMD, both, P&amp;lt; 0.05). However, when a PI3K inhibitor was used, the cardiac protective effects of UTMD treatment were largely eliminated. EF and FS deteriorated significantly (EF: HF+UTMD+LY294002: 42.84±2.88% vs. HF+LY294002: 32.73±3.05%, P&amp;lt;0.0001; FS: HF+UTMD+LY294002: 21.94±1.69% vs. HF+LY294002: 16.36±1.76%, P&amp;lt;0.0001), and the production of NO and ATP decreased significantly (HF+UTMD+LY294002 vs. HF+LY294002, both, P&amp;lt; 0.05). Conclusion The UTMD-mediated cavitation effect can rapidly improve the cardiac function of ischemic heart failure rats by activating PI3K/Akt/eNOS signaling pathway and promoting the release of NO and ATP.

Identification of immune-related genes for the diagnosis of ischemic heart failure based on bioinformatics

The role of immune cells in the pathogenesis of ischemic heart failure (IHF) is well-established. However, identifying key genes in patients with IHF remains a challenge. We obtained two IHF datasets from the GEO database (GSE76701 and GSE21610), and identified four potential diagnostic candidate genes for IHF by using bioinformatics and machine learning algorithms, namely RNASE2, MFAP4, CHRDL1, and KCNN3. We constructed nomogram and validated the diagnostic value of these genes on additional GEO datasets (GSE57338). The results showed that these four genes had high diagnostic value (area under the curve value of 0.961). Furthermore, our immune infiltration analysis revealed the presence of three dysregulated immune cells in IHF, namely macrophages M2, monocytes, and Tcells gamma delta. We also explored the potential molecular mechanisms of IHF. These findings provide new insights into the pathogenesis, diagnosis, and treatment of IHF.

Influence and risk factors of postoperative infection after surgery for ischemic cardiomyopathy.

Studies on postoperative infection (POI) after surgery for ischemic cardiomyopathy are still lacking. This study aimed to investigate the risk factors of POI and its influence on clinical outcomes in patients undergoing ischemic cardiomyopathy surgery. The Surgical Treatment for Ischemic Heart Failure (STICH) trial randomized patients with ischemic cardiomyopathy [coronary artery disease (CAD) with left ventricular ejection fraction ≤35%] to surgical and medical therapy. In this study, a post hoc analysis of the STICH trial was performed to assess the risk factors and clinical outcomes of POI in those undergoing coronary artery bypass graft (CABG). Patients were divided according to whether POI developed during hospitalization or within 30 days from operation. Of the 2,136 patients randomized, 1,460 patients undergoing CABG per-protocol was included, with a POI rate of 10.2% (149/1,460). By multivariable analysis, POI was significantly related to patients' age, body mass index, depression, chronic renal insufficiency, Duke CAD Index, and mitral valve procedure. Compared to patients without POI, patients with POI had significantly longer durations of intubation, CCU/ICU and hospital stay, and higher rates of re-operation, in-hospital death and failed discharge within 30 days postoperatively. In addition, these patients had significantly higher risks of all-cause death, cardiovascular death, heart failure death, and all-cause hospitalization during long-term follow-up. However, the influence of POI on all-cause death was mainly found during the first year after operation, and the influence was not significant for patients surviving for more than 1 year. POI was prevalent after surgery for ischemic cardiomyopathy and was closely related to short-term and long-term clinical outcomes, and the effect of POI mainly occurred within the first postoperative year. This study first reported and clarified the relationship between POI and long-term prognosis and the predictors for POI after surgery for ischemic cardiomyopathy worldwide, which may have certain guiding significance for clinical practice. https://www.clinicaltrials.gov, identifier (NCT00023595).

AATS 2023: Left ventricular restoration with scar exclusion in the surgical treatment for ischemic heart failure

ObjectivePost-infarction myocardial scar as detected by cardiac magnetic resonance (CMR) is associated with adverse left ventricular (LV) remodeling and negatively affects the prognosis. We sought to analyze the impact of left ventricular restoration (LVR) with asynergic scar exclusion on long-term outcomes for patients with ischemic heart failure (IHF). MethodsFrom January 2005, 134 consecutive patients with IHF underwent scar-exclusive LVR. Among the 131 survivors, 108 patients had paired late gadolinium enhancement (LGE)-CMR preoperatively and one year after, and represent the study population. Patients were divided into two groups according to whether their post-LVR residual percentage of scarred LV perimeter was <35% (%Scar <35; n = 55) or more (%Scar ≥35; n = 53). We compared the two groups, by looking at LGE-CMR outcomes, and at long-term survival and cardiac event (hospitalization for cardiac causes)-free survival. ResultsPostoperative LV end-systolic volume index decreased significantly and ejection fraction increased with significant increase in stroke volume index (P < 0.05 for both). LV diastolic function of the left atrial volume index was significantly improved in patients with residual %Scar <35 than in those with %Scar ≥35 (P interaction = 0.005). Median survival in patients with residual %Scar <35 and ≥ 35 were 8.3 (4.5–12.2) years and 6.8 (1.8–11.8) years respectively (P = 0.106). Median cardiac event-free survival in patients with %Scar <35 and ≥ 35 were 8.0 (3.9–12.1) years and 4.8 (0.8–8.8) years respectively (P < 0.001). ConclusionsScar-exclusive LVR yielded sustainable improvement in LV function and favorable long-term survival regardless of the extent of residual scar. The LVR should be performed to attain scar exclusion in the surgical treatment for IHF, which in turn might protectively affect LV diastolic function and cardiac event-free survival.

Understanding the role of coronary artery revascularization in patients with left ventricular dysfunction and multivessel disease.

Coronary artery disease (CAD) is the most common cause of heart failure with reduced ejection fraction (HFrEF). Advances and innovations in medical therapy have been shown to play a crucial role in improving the prognosis of patients with CAD and HFrEF; however, mortality rate in these patients remains high, and the role of surgical and/or percutaneous revascularization strategy is still debated. The Surgical Treatment for Ischemic Heart Failure (STICH) trial and the Revascularization for Ischemic Ventricular Dysfunction (REVIVED) trial have attempted to provide an answer to this issue. Nevertheless, the results of these two trials have generated further uncertainties. Their findings do not provide a definitive answer about the ideal clinical phenotype for surgical or percutaneous coronary revascularization and dispute the historical dogma on myocardial viability and the theory of myocardial hibernation, raising new questions about the proper selection of patients who are candidates for coronary revascularization. The aim of this review is to provide an overview on the actual available evidence of coronary artery revascularization in patients with CAD and left ventricular dysfunction and to suggest new insights on the proper selection and management strategies in this high-risk clinical setting.

MiR-155 regulates macrophage polarization and alleviates myocardial fibrosis through paracrine secretion of transforming growth factor-beta 1 in ischemic heart failure

This study investigated the mechanism underlying miR-155 in ischemic heart failure. The left ventricular ejection fraction (LVEF) in rats was detected by color Doppler echocardiography. After the myocardial tissues were stained with Masson and Sirius red respectively, TGF-β expression was detected by immunohistochemical staining. Additionally, rat cardiomyocytes were transfected with miR-155 inhibitor, miR-155 mimic, TGF-β agonist or TGF-β inhibitor followed by analysis of levels of miR-155 and TGF-β by real time quantitative PCR. M1 polarization index of lipopolysaccharides (LPS) and M2 type polarization indexes of IL-4, IL-10, and TGF-β were examined by western blot. Among the three groups of rats, the LVEF of rats in model group was the lowest (p &lt; 0.05) but it was elevated in miR-155 group, whilst the accumulated collagen fibers and hyperplasia in the myocardium were reduced upon miR-155 treatment. Of note, the myocardial tissue of modeled rats had the highest TGF-β level, but miR-155 overexpression or inhibitor dramatically decreased TGF-β level as well as protein expressions of LPS, IL-4, IL-10, and TGF-β, with the lowest level in miR-155 group. Interestingly, TGF-β agonist treatment resulted in a decrease in LPS while IL-4, IL-10, and TGF-β inhibitor caused opposite outcome. miR-155 can regulate the level of macrophage polarization and paracrine TGF-β and overexpressed miR-155 abrogates the effect of TGF-β on cardiac fibers, alleviating the myocardial ischemic in heart failure. TGF-β can also affect the biological function of LPS. miR-155 might become a target for the treatment of ischemic heart failure and myocardial fibrosis.

Myocardial Revascularization in Patients With Ischemic Cardiomyopathy: For Whom and How.

Background Myocardial revascularization has been advocated to improve myocardial function and prognosis in ischemic cardiomyopathy (ICM). We discuss the evidence for revascularization in patients with ICM and the role of ischemia and viability detection in guiding treatment. Methods and Results We searched for randomized controlled trials evaluating the prognostic impact of revascularization in ICM and the value of viability imaging for patient management. Out of 1397 publications, 4 randomized controlled trials were included, enrolling 2480 patients. Three trials (HEART [Heart Failure Revascularisation Trial], STICH [Surgical Treatment for Ischemic Heart Failure], and REVIVED [REVascularization for Ischemic VEntricular Dysfunction]-BCIS2) randomized patients to revascularization or optimal medical therapy. HEART was stopped prematurely without showing any significant difference between treatment strategies. STICH showed a 16% lower mortality with bypass surgery compared with optimal medical therapy at a median follow-up of 9.8 years. However, neither the presence/extent of left ventricle viability nor ischemia interacted with treatment outcomes. REVIVED-BCIS2 showed no difference in the primary end point between percutaneous revascularization or optimal medical therapy. PARR-2 (Positron Emission Tomography and Recovery Following Revascularization) randomized patients to imaging-guided revascularization versus standard care, with neutral results overall. Information regarding the consistency of patient management with viability testing results was available in ≈65% of patients (n=1623). No difference in survival was revealed according to adherence or no adherence to viability imaging. Conclusions In ICM, the largest randomized controlled trial, STICH, suggests that surgical revascularization improves patients' prognosis at long-term follow-up, whereas evidence supports no benefit of percutaneous coronary intervention. Data from randomized controlled trials do not support myocardial ischemia or viability testing for treatment guidance. We propose an algorithm for the workup of patients with ICM considering clinical presentation, imaging results, and surgical risk.

Surgical or percutaneous coronary revascularization for heart failure: an in silico model using routinely collected health data to emulate a clinical trial.

The choice of revascularization with coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) in people with ischaemic left ventricular dysfunction is not guided by high-quality evidence. A trial of CABG vs. PCI in people with heart failure (HF) was modelled in silico using routinely collected healthcare data. The in silico trial cohort was selected by matching the target trial cohort, identified from Hospital Episode Statistics in England, with individual patient data from the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Allocation to CABG vs. complex PCI demonstrated random variation across administrative regions in England and was a valid statistical instrument. The primary outcome was 5-year all-cause mortality or cardiovascular hospitalization. Instrumental variable analysis (IVA) was used for the primary analysis. Results were expressed as average treatment effects (ATEs) with 95 confidence intervals (CIs). The target population included 13 519 HF patients undergoing CABG or complex PCI between April 2009 and March 2015. After matching, the emulated trial cohort included 2046 patients. The unadjusted primary outcome rate was 51.1 in the CABG group and 70.0 in the PCI group. IVA of the emulated cohort showed that CABG was associated with a lower risk of the primary outcome (ATE 16.2, 95 CI 20.6 to 11.8), with comparable estimates in the unmatched target population (ATE 15.5, 95 CI 17.5 to 13.5). In people with HF, in silico modelling suggests that CABG is associated with fewer deaths or cardiovascular hospitalizations at 5 years vs. complex PCI. A pragmatic clinical trial is needed to test this hypothesis and this trial would be feasible.

Perioperative changes in left ventricular systolic function following surgical revascularization.

Nearly 1/3rd of patients undergoing coronary artery bypass graft surgery (CABG) have left ventricular systolic dysfunction. However, the extent, direction and implications of perioperative changes in left ventricular ejection fraction (LVEF) have not been well characterized in these patients. We studied the changes in LVEF among 549 patients with left ventricular systolic dysfunction (LVEF &lt;50%) who underwent CABG as part of the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Patients had pre- and post-CABG (4 month) LVEF assessments using identical cardiac imaging modality, interpreted at a core laboratory. An absolute change of &gt;10% in LVEF was considered clinically significant. Of the 549 patients (mean age 61.4±9.55 years, and 72 [13.1%] women), 145 (26.4%) had a &gt;10% improvement in LVEF, 369 (67.2%) had no change and 35 (6.4%) had &gt;10% worsening of LVEF following CABG. Patients with lower preoperative LVEF were more likely to experience an improvement after CABG (odds ratio 1.36; 95% CI 1.21-1.53; per 5% lower preoperative LVEF; p &lt;0.001). Notably, incidence of postoperative improvement in LVEF was not influenced by presence, nor absence, of myocardial viability (25.5% vs. 28.3% respectively, p = 0.67). After adjusting for age, sex, baseline LVEF, and NYHA Class, a &gt;10% improvement in LVEF after CABG was associated with a 57% lower risk of all-cause mortality (HR: 0.43, 95% CI: 0.26-0.71). Among patients with ischemic cardiomyopathy undergoing CABG, 26.4% had &gt;10% improvement in LVEF. An improvement in LVEF was more likely in patients with lower preoperative LVEF and was associated with improved long-term survival.

Systolic blood pressure time in range and long-term clinical outcomes in patients with ischaemic cardiomyopathy

Abstract Background The relationship between systolic blood pressure (SBP) control and long-term clinical outcomes in patients with ischaemic cardiomyopathy remains unclear. It has been previously reported that either too high or too low SBP may lead to a poorer prognosis. But current SBP control metrics may not take into account the possible effects of fluctuating SBP overtime on patients. Purpose This study aimed to estimate the association between time in range (TIR) of SBP and long-term clinical outcomes in patients with ischaemic cardiomyopathy. Methods This study was a post-hoc analysis of The Surgical Treatment of Ischaemic Heart Failure (STICH) trial, a randomized controlled trial with two hypotheses that enrolled participants with coronary artery disease and left ventricular ejection fraction ≤35%. The SBP target range of the TIR was defined as 110 to 130 mmHg and the SBP TIR was calculated by linear interpolation method. Patients were equally divided into four groups by quartiles of TIR. Multivariable-adjusted Cox proportional hazards regression models were constructed to compare the effects of different levels of TIR on a 10-year prognosis. The primary outcome was all-cause mortality. Subgroup analyses were performed according to whether patients were assigned to coronary artery bypass grafting (CABG) or medical therapy (MED), and in populations with different baseline SBP. Results A total of 1194 eligible patients were included according to the purpose of our study. Compared with patients in the quartile 4 group (TIR 77.87–100%), the fully adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of all-cause mortality were 1.32 (0.98–1.78) for quartile 3 group (TIR 54.81–77.63%), 1.40 (1.03–1.90) for quartile 2 group (TIR 32.59–54.67%), and 1.53 (1.14–2.04) for quartile 1 group (TIR 0–32.56%) (P for trend = 0.005). When evaluated TIR as a continuous variable, per 1-SD decrement (29.28%) in TIR significantly increased the incidence of all-cause mortality [1.15 (1.04–1.26)]. Similarly, the decrement in TIR significantly elevated the risk of cardiovascular (CV) mortality and the risk of all-cause mortality plus CV rehospitalization. Consistent results were also observed in subgroup analyses of either CABG or MED, or different baseline SBP, indicating the robustness of our findings. Conclusions This study suggested that in patients with ischaemic cardiomyopathy, a higher SBP TIR was significantly associated with a decreased risk of all-cause mortality, CV mortality and the composite of all-cause mortality plus CV rehospitalization, regardless of whether the patient received CABG or MED, and the level of baseline SBP. Our findings support that TIR might be a substitutable metric of SBP control for long-term clinical outcomes in patients with ischaemic cardiomyopathy. Funding Acknowledgement Type of funding sources: None.

POTENTIAL CARDIOPROTECTIVE EFFECT OF GENIPIN VIA CYCLOOXIDASE 2 SUPPRESSION AND P53 SIGNAL PATHWAY ATTENUATION IN INDUCED MYOCARDIAL INFARCTION IN RATS.

Background and aims: Genipin, an iridoid derived from geniposide by β-glucosidase hydrolysis, has shown potential benefit in the treatment of heart function insufficiency despite its unclear therapeutic mechanism. This study aimed to investigate the primary cardioprotective mechanism of genipin. We hypothesized that genipin demonstrated the antiapoptosis and anti-inflammation for cardiac protection by inhibiting the cyclooxidase 2 (COX2)-prostaglandin D2 (PGD2) and murine double minute 2 (MDM2)-p53 pathways. Methods: The normal Sprague-Dawley rats were made into myocardial infarction models by conventional methods. Animals were treated with genipin for 5 weeks after myocardial infarction (MI). Morphometric and hemodynamic measurements were performed 5 weeks post-MI. Biological and molecular experiments were performed after the termination. Results: Both morphometry and hemodynamics in systole and diastole were significantly impaired in the model group but restored close to basal level after treatment with genipin. Genipin also restored the post-MI upregulated expressions of cytochrome c, p53, COX2, and PGD2 and downregulated expression of MDM2 to the approximate baseline. Genipin inhibited apoptotic and inflammatory pathways to prevent post-MI structure-function remodeling. Conclusions: This study showed the cardioprotective mechanism of genipin and implied its potential clinical application for the treatment of ischemic heart failure.

Evolution and clinical implications of right ventricular dysfunction in ischemic cardiomyopathy with or without coronary artery bypass surgery

Abstract Background The Surgical Treatment of Ischemic Heart Failure (STICH) trial demonstrated that coronary artery bypass grafting (CABG) provides additional survival benefits to patients with ischemic cardiomyopathy. However, it remains unclear whether this benefit is affected by preoperative right ventricular (RV) function and how post-therapeutic evolution of RV function influences long-term outcomes. Purpose We sought to investigate the implications of baseline RV function on therapeutic decision-making in patients with ischemic cardiomyopathy, and to evaluate the prognostic implications of post-therapeutic evolution of RV function. Methods Patients with available baseline echocardiographic RV function assessed by experienced Echocardiography Core Laboratory physicians were included from the hypothesis 1 of the STICH trial. The primary outcome was long-term all-cause mortality. Results A total of 1042 patients were included, among them 757 (72.7%) had normal RV function, 143 (13.7%) mild right ventricular dysfunction (RVD), and 142 (13.6%) moderate to severe RVD. After a median follow-up of 9.8 years, patients with RVD had a higher risk of all-cause mortality compared with patients with normal RV function [mild RVD: adjusted hazard ratio (aHR) 1.32; 95% confidence interval (CI) 1.06–1.64; moderate to severe RVD: aHR, 1.74; 95% CI 1.39–2.18]. Although no significant interaction was detected between RVD degree and treatment allocation (P for interaction = 0.399), a gradually decreasing survival benefit associated with CABG was observed among patients with normal RV function (aHR: 0.79; 95% CI: 0.65–0.96), mild RVD (aHR: 0.85; 95% CI: 0.56–1.29), and moderate to severe RVD (aHR: 0.97; 95% CI: 0.67–1.43). Among 746 patients with available RV function assessed at baseline and post-therapeutic 4-month follow-up, there was a gradient of increasing risk for all-cause mortality across patients with consistent normal RV function, recovery of RVD (aHR: 1.20; 95% CI: 0.88–1.64), newly developed RVD (aHR: 1.59; 95% CI: 1.18–2.14), and consistent RVD (aHR: 2.06; 95% CI: 1.60–2.67). Independent predictors of RVD recovery included baseline left ventricular ejection fraction (per 1-percent increment, adjusted odds ratio: 1.04; 95% CI: 1.00–1.09) and mitral regurgitation ≥ grade 2 (adjusted odds ratio: 0.42; 95% CI: 0.21–0.84). Conclusions Baseline RVD was associated with an increased risk of long-term mortality in patients with ischemic cardiomyopathy, and adding CABG to medical therapy might provide limited survival benefits in patients with moderate to severe RVD. A gradient of increasing risk for mortality was observed across different categories of RV function evolution, which emphasizes the necessity of pre- and post-therapeutic RV assessment for prognostic evaluation. Funding Acknowledgement Type of funding sources: None.

Is the world ready for the STICH 3.0 trial?

Coronary artery disease (CAD) is responsible for >50% of heart failures cases. Patients with ischemic left ventricular systolic dysfunction (iLVSD) are known to have poorer outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) compared to patients with a normal ejection fraction. Nevertheless, <1% of patients in coronary revascularization trials to date had iLVSD. The purpose of this review is to describe coronary revascularization modalities in patients with iLVSD and highlight the need for randomized controlled trial evidence comparing these treatments in this patient population. Network meta-analytic findings of observational studies suggest that PCI is associated with higher rates of mortality, cardiac death, myocardial infarction, and repeat revascularization but not stroke compared to CABG in iLVSD. In recent years, outcomes for patients undergoing PCI have improved as a result of advances in technologies and techniques. The optimal coronary revascularization modality in patients with iLVSD remains unknown. In observational studies, CABG appears superior to PCI; however, direct randomized evidence is absent and developments in PCI techniques have improved post-PCI outcomes in recent years. The Surgical Treatment for Ischemic Heart Failure 3.0 consortium of trials will seek to address the clinical equipoise in coronary revascularization in patients with iLVSD.

Tc-99m Sestamibi Myocardial Perfusion Imaging After Coronary Artery Bypass Grafting for Ischemic Heart Failure

Heart failure (HF), a clinical syndrome most commonly occurring due to ischemic heart disease, causes significant morbidity and mortality. The benefits of revascularization versus medical treatment for ischemic heart failure remain controversial. Thus, we assessed a patient diagnosed with ischemic heart failure before and 3 months after coronary artery bypass grafting by myocardial radionuclide imaging. Findings of Tc-99m sestamibi myocardial perfusion imaging revealed that the degree and area of ischemia were significantly reduced, and the systolic function of the left ventricle improved compared with the preoperative value. This suggests the benefit of revascularization in cases of ischemic heart failure.

Midterm Outcome of Hybrid Transcatheter and Minimally Invasive Left Ventricular Reconstruction for the Treatment of Ischemic Heart Failure

BackgroundLeft ventricular (LV) remodeling after anterior myocardial infarction (AMI) can cause a pathological increase in LV volume, reduction in LV ejection fraction (EF), and symptomatic heart failure (HF). This study evaluates the midterm results of a hybrid transcatheter and minimally invasive surgical technique to reconstruct the negatively remodeled LV by myocardial scar plication and exclusion with microanchoring technology. MethodsRetrospective single-center analysis of patients who underwent hybrid LV reconstruction (LVR) with the Revivent TransCatheter System. Patients were accepted for the procedure when they presented with symptomatic HF (New York Heart Association class ≥ II, EF < 40%) after AMI, in the presence of a dilated LV with either akinetic or dyskinetic scar in the anteroseptal wall and/or apex of ≥50% transmurality. ResultsBetween October 2016 and November 2021, 30 consecutive patients were operated. Procedural success was 100%. Comparing echocardiographic data preoperatively and directly postoperatively, LVEF increased from 33 ± 8% to 44 ± 10% (p < 0.0001). LV end-systolic volume index decreased from 58 ± 24 mL/m2 to 34 ± 19 mL/m2 (p < 0.0001) and LV end-diastolic volume index decreased from 84 ± 32 mL/m2 to 58 ± 25 mL/m2 (p < 0.0001). Hospital mortality was 0%. After a mean follow-up of 3.4 ± 1.3 years, there was a significant improvement of New York Heart Association class (p = 0.001) with 76% of surviving patients in class I-II. ConclusionsHybrid LVR for symptomatic HF after AMI is safe and results in significant improvement in EF, reduction in LV volumes, and sustained improvement in symptoms.

Left ventricular volume change and long-term outcomes in ischaemic cardiomyopathy with or without surgical revascularisation: A post-hoc analysis of a randomised controlled trial.

SummaryBackgroundWhether the association between post-therapeutic left ventricular volume change and long-term outcomes in ischaemic cardiomyopathy is influenced by the performance of coronary artery bypass grafting (CABG) remains unclear. We sought to perform a post-hoc analysis of the Surgical Treatment of Ischaemic Heart Failure (STICH) trial to investigate this association in patients treated with medical therapy (MED) with or without CABG.MethodsFrom July 24, 2002, to May 5, 2007, 1212 patients with ischaemic cardiomyopathy were enrolled in the STICH trial (NCT00023595) from 99 sites in 22 countries, and were randomly assigned to undergo CABG plus MED or MED alone. We completed a post-hoc analysis of this trial. Patients with paired left ventricular end-systolic volume index (ESVI) measured at baseline and 4-months were included in our analysis. The association between change in ESVI from baseline to 4-months and cardiovascular mortality or all-cause mortality was assessed in MED arm and CABG plus MED arm.Findings523 patients were included, with 291 (55.6%) assigned to MED arm and 232 (44.4%) to CABG plus MED arm. At a 4-month follow-up, ESVI reduction was more likely to occur among patients undergoing CABG plus MED. After a median follow-up of 10.3 years, for each 26% (1- standard deviation) decrement in ESVI, it was associated with a 22% lower risk of cardiovascular mortality (HR 0.78; 95% CI, 0.65-0.94) and 19% lower risk of all-cause mortality (HR 0.81; 95% CI, 0.69-0.95) in MED arm, whereas this association was not shown in CABG plus MED arm (cardiovascular mortality: HR 0.90; 95%CI, 0.74-1.10; all-cause mortality: HR 0.93; 95%CI, 0.79-1.09). A 16% reduction in ESVI was determined to be the most appropriate threshold of change in ESVI in the MED arm.InterpretationIn patients with ischaemic cardiomyopathy, left ventricular volume change was associated with long-term prognosis after medical therapy alone, whereas was likely not an optimal benchmark for evaluating the survival benefits associated with CABG. A more than 16% reduction in ESVI might assist in therapeutic efficacy assessment and prognostic evaluation in medically treated patients.FundingNational Natural Science Foundation of China; Natural Science Funds of Guangdong Province.

Identifying quality of life outcome patterns to inform treatment choices in ischemic cardiomyopathy

BackgroundThe Surgical Treatment for Ischemic Heart Failure (STICH) trial found that routine use of coronary artery bypass surgery (CABG) improved mean quality of life (QoL) scores relative to guideline-directed medical therapy (GDMT) in patients with ischemic cardiomyopathy. However, mean differences in QoL scores do not provide what patients want to know when facing a high-risk/high-benefit treatment choice. MethodsWe analyzed Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary scores in CABG and GDMT patients over 36 months using a combination of statistical methods to group QoL data into clinically relevant outcome patterns (phenotype trajectories) and to then identify the main baseline predictors of each phenotype. QoL outcome phenotypes were developed using mixture models to define the dominant phenotype trajectories present in STICH QoL data. Logistic regression models were used to predict each patient's probability of achieving each outcome pattern with each treatment. ResultsIn STICH, 592 patients underwent CABG and 607 were managed with GDMT. Our analyses identified 3 phenotype trajectory patterns in both treatment groups. Two of the 3 trajectories showed improving patterns, and were classified as “good QoL trajectories,” seen in 498 (84.1%) CABG and 449 (73.9%) GDMT patients. Defining a consequential CABG-GDMT treatment difference as a >10% higher absolute predicted probability of belonging to good QoL trajectories, 277 (23.5%) patients were more likely to have good outcome with CABG while 45 (3.8%) patients were more likely to have a good outcome with GDMT. For 644 (54.7%) patients, CABG and GDMT probabilities of a good outcome were within 5% of each other. ConclusionsThe pattern of QoL outcomes after CABG compared with GDMT in STICH followed 3 main phenotypic trajectories, which could be predicted based on individual baseline features. Patient-specific predictions about expected QoL outcomes with different treatment choices provide an intuitive framework for personalizing patient decision making.

Ischemic Heart Failure: About 140 Cases

Ischemic heart failure is a major public health problem because of its frequency and its consequences in terms of morbidity and mortality. The incidence and prevalence of ischemic heart failure are increasing because of the aging of the population, but also because of better management of ischemic heart disease. The management of ischemic heart failure has become easier with diagnostic advances and the advent of new cardiac imaging techniques as well as therapeutic advances (inhibition of neurohormonal activation and ventricular remodeling, myocardial revascularization). In our study, we have essentially tried to highlight the different risk factors of ischemic heart failure but also some of its clinical, paraclinical, and therapeutic aspects. The treatment of ischemic heart failure in our context is in accordance with the literature, highlighting the interest of primary prevention consisting of the management of cardiovascular risk factors and the optimization of the drug treatment of these patients.