Changes In Ventricular Ejection Fraction Research Articles

Pharmacotherapy in patients with heart failure with reduced ejection fraction: A systematic review and meta-analysis.

Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated. PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI). We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI+BB+MRA+SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI+BB+MRA+SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI+BB+MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle "ACEI+BB+MRA" in improving LVEF. ACEI+BB+MRA+SGLT-2i was better than ACEI+BB+MRA (-8.05mL/m2, 95% CI: -14.88 to -1.23mL/m2) and ACEI+BB+SGLT-2i (-18.94mL/m2, 95% CI: -36.97 to -0.61mL/m2) in improving LVEDVI. ACEI+BB+MRA+SGLT-2i (-3254.21 pg/mL, 95% CI: -6242.19 to -560.47 pg/mL) was superior to ARB+BB+MRA in reducing NT-proBNP. Adding SGLT-2i to ARNI/ACEI+BB+MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI+BB+MRA+SGLT-2i" is superior to the golden triangle "ACEI+BB+MRA" in improving LVEF. PROSPERO; No. CRD42022354792.

Clinical characteristics of patients with better ejection fraction recovery after upgrading to cardiac resynchronization therapy

Abstract Background Chronic right ventricular (RV) pacing can cause cardiac systolic dysfunction and heart failure (HF), increased risk of HF hospitalization and adverse outcomes. In these patients upgrading to cardiac resynchronization therapy (CRT) may improve left ventricular function. Purpose We aimed to identify the profile of patients (their clinical, electrical and echocardiographic characteristics) who are more likely to make a significant change in left ventricular ejection fraction (LVEF) one year after revision of the RV pacing system to CRT. Methods This was a retrospective, observational, single-center study. We included patients with a permanent antibradycardia pacemaker who had no systolic dysfunction and HF symptoms at the time of pacemaker implantation and who experienced a drop in LVEF below 35% during follow-up, with development of HF symptoms and with at least 20% of ventricular pacing. In all patient's revision to CRT was performed at our center between January 2014 and December 2019. We excluded patients who were indicated for a system upgrade regardless of the percentage of ventricular pacing and those in whom the drop in LVEF is due to a new coronary event. We used patients’ medical records to collect data on baseline characteristics. LVEF was measured pre-revision and 12 months after upgrade. To examine the difference in LVEF change between specified subgroups of patients we used a t-test. Results During the defined period, 82 upgrade procedures from conventional pacemaker to CRT were done in our center. We excluded 12 patients with left bundle branch block (LBBB) QRS morphology, 4 with non-LBBB QRS morphology but with QRS duration over 150ms and 4 patients who died within a year after revision to CRT. Therefore, we analyzed 62 patients (20.9% female, mean age 66.9 ± 11.2 years, mean LVEF 25.9 ± 6.8). After 12 months, 58.1% of patients had an increase in EF above 5%, and the mean change in LVEF (ΔLVEF) was 7.8 ± 11.8. Compared to those with non-ischemic cardiomyopathy (NICMP), patients with ischemic etiology had statistically significantly less improvement in LVEF (ΔLVEF 1.8 ± 6.8 vs 13.1 ± 12.7, p < 0.01), as well as patients with an RV apical pacing compared to those with a septal lead position (ΔLVEF 5.1 ± 9.1 vs 14.1 ± 14.7, p = 0.021). Patients with narrower paced QRS complex (<150ms) before upgrade had a significantly greater improvement in LVEF compared to those with a wider paced QRS complex (≥150ms) (ΔLVEF 10.9 ± 12.2 vs 4.8 ± 10.7, p = 0.04), and those with post-revision paced QRS width above 150ms had significantly lower change in LVEF compared to those with a narrower paced QRS (ΔLVEF 4.6 ± 9.8 vs 11.1 ± 12.8, p = 0.028). Conclusion Patients with NICMP and with width of the paced QRS complex before and after revision to CRT below 150ms had significantly greater improvement in LVEF 12 months after the upgrade. The position of RV lead significantly affects the success of the upgrade procedure.

Clinical performance and safety of a two-lead cardiac resynchronization therapy system with a floating atrial sensing dipole

Abstract Background The incidence of complications after implantable cardioverter-defibrillator (ICD) and cardiac resynchronisation therapy (CRT-D) implantations is dependent on the number of implanted leads. The majority of CRT-D patients have unimpaired sinus node function and do not require atrial pacing. A two-lead CRT-D system with a floating atrial sensing dipole mounted on the right ventricular lead ((CRT-DX) allows dual chamber tachyarrhythmia detection, and atrio-ventricular sequential pacing with a reduced amount of implanted material. Purpose This study investigated the clinical efficacy and safety of the CRT-DX system. Methods This multicentre, single-arm study observed patients after de novo implantation of a CRT-DX system for 12 months. Patients were eligible for the study when chronotropic competence was proven by heart rates ≥100 bpm during exercise, premature ventricular contractions rate of < 5%/h and absence of atrioventricular block ≥ II. Intraoperatively measured p-wave amplitude of ≥ 1 mV was recommended. The primary safety endpoint was the additional implantation of a right atrial (RA) lead after the initial implantation. As indicators of efficacy, we report the changes in left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) class over the follow-up period. Results Overall, 110 patients were implanted with the complete CRT-DX system. Mean age of study participants was 62 ± 12 years and 77 (70%) were male. The underlying heart disease was non-ischemic in 66 (60%) patients and 103 (93%) had a left bundle branch block. NYHA class was II in 60 (54.5%) and III in 50 (45.5%) patients. ICD placement was performed in 13 (11.8%) patients for the secondary prevention of sudden cardiac death. A total of 104 patients completed the follow-up, 2 patients died, 1 had the system explanted for infection, 2 withdrew consent and 1 was lost to follow-up. The primary endpoint of RA lead implantation was met in 2 (1.8%) participants (Figure 1). One patient required atrial pacing and one patient, who had shown a p-wave amplitude < 1 mV at implantation, lost atrial sensing. The mean RA sensing amplitude remained stable during follow-up (4.6 ± 1.8 mV, 4.9 ± 1.8 mV and 4.6 ± 1.8 mV at 1, 6 and 12 months, respectively; Figure 2). The LVEF improved by 14.7% ± 11.0%, from 26.3% ± 6.9% to 40.8% ± 10.7% (p < 0.00001). Changes in NYHA class were available in 87 patients with 35 (40.2%) improved by one class and 13 (14.9 %) by two classes. Thirty-four (39.1%) had no change and 5 (5.7%) worsened by one class (global p < 0.00001). Conclusion The two-lead CRT-DX system showed a low requirement of subsequent RA lead implantations (1.8%) and stable RA sensing amplitudes. Our results suggest a CRT response similar to that of conventional three-lead CRT-D systems. CRT-DX systems appear to be a feasible alternative for patients with chronotropic competence.Kaplan-Meier curve for primary endpointDaily mean RA sensing amplitude

Effect of Radiotherapy on the Right Ventricular Function in Lung Cancer Patients.

Anticancer treatment is associated with many side effects, including those involving the cardiovascular system. While many studies are available on the effects of radiotherapy (RT) on the left ventricle (LV), studies are lacking on the early effects of RT on the structure and function of the right ventricle (RV). Our study aims to assess, using modern echocardiographic techniques, the effect of irradiation on RV systolic function in the mid-term follow-up of patients undergoing RT for lung cancer (LC). This single-center, prospective study included consecutive patients with LC who were referred for treatment with definite radiotherapy and chemotherapy (study group) or chemotherapy only (control group). The study included 43 patients with a mean age of 64.9 ± 8.1 years. Cancer treatment-related RV toxicity (CTR-RVT) was found in 17 patients (40%). Early reductions in TAPSE values were observed among patients in the study group (20.3 mm vs. 22.1 mm, p = 0.021). Compared to baseline, there was a significant reduction in RV global longitudinal strain (RV GLS) in the study group immediately after the treatment (-21.1% vs. -18.4%, p = 0.02) and also at 3 months after RT (-21.1% vs. -19.1%, p = 0.021). A significant reduction in the RV FWLS value was also observed at 3 months after the end of the treatment (-23.8% vs. -21.8, p = 0.046). There were no significant changes in the three-dimensional right ventricular ejection fraction (3DRVEF) during the follow-up. We found a correlation (p = 0.003) between the mean dose of radiation to the RV and 3DRVEF when assessed immediately after RT. The mean dose of radiation to the heart correlated with RV free-wall longitudinal strain (RV FWLS) immediately after RT (p = 0.03). RV cardiotoxicity occurs in nearly half of patients treated for lung cancer. TAPSE is an important marker of deterioration of RV function under LC treatment. Compared to 3DRVEF, speckle tracking echocardiography is more useful in revealing deterioration of RV systolic function after radiotherapy.

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.

Improvement in Left Ventricular Function of the Resected Myocardium after Septal Myectomy in Patients with Aortic Valve Replacement

Background: Some surgeons have previously advocated for a more aggressive concomitant septal myectomy to address left ventricular outflow tract obstruction; however, concerns about the surgical complications of post-septal myectomy remain. Here, we aimed to assess the clinical, echocardiographic, and pathological findings following concomitant septal myectomy with surgical aortic valve replacement. Methods: We reviewed 21 patients who underwent surgical aortic valve replacement and concomitant septal myectomy from April 2014 to September 2019. The global and regional left ventricular ejection fraction changes between the perioperative periods were analyzed using two-dimensional speckle-tracking echocardiography. The resected myocardium was pathologically assessed. Results: No operative mortality was observed during the study period. Transthoracic echocardiography showed no significant differences in preoperative and postoperative left ventricular ejection fraction (68.1 ± 9.9% vs. 68.6 ± 6.0%, p = 0.82) or interventricular septum thickness (11.9 ± 1.4 mm vs. 11.5 ± 1.5 mm, p = 0.23). Interventricular septum thickness at the end-systolic phase, which is the maximum septal wall thickness, was significantly reduced postoperatively (27.7 ± 9.3 mm vs. 22.6 ± 5.5 mm, p < 0.05). The basal, mid, and apical septal areas improved with septal myectomy by 80%, 230%, and 27%, respectively, compared to perioperative echocardiography (basal septal, 80 ± 23%; mid septal, 230 ± 830%; apical septal, 27 ± 350%). Pathological examination of the resected myocardium revealed marked endocardial thickness (mean, 914 µm) with focal fibrosis. Conclusions: In aortic valve stenosis patients with septal hypertrophy, concomitant septal myectomy with surgical aortic valve replacement improved regional myocardial function and eliminated left ventricular outflow tract obstruction by removing thickened endocardium and prominent fibrosis.

A Comparison of the Association of Septal Scar Burden on Responses to LBBAP-CRT and BVP-CRT.

Left bundle branch area pacing (LBBAP) is an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). However, despite the presence of left bundle branch block, whether cardiac substrate may influence the effect between the 2 strategies is unclear. This study aims to assess the association of septal scar on reverse remodeling and clinical outcomes of LBBAP compared with BVP. We analyzed patients with nonischemic cardiomyopathy who had CRT indications undergoing preprocedure cardiac magnetic resonance examination. Changes in left ventricular ejection fraction (LVEF) and echocardiographic response (ER,≥5% absolute LVEF increase) were assessed at 6months. The clinical outcome was the composite of all-cause mortality, heart failure hospitalization, or major ventricular arrhythmia. There were 147 patients included (51 LBBAP and 96 BVP). Among patients with low septal scar burden (below median 5.7%, range: 0 to 5.3%), LVEF improvement was higher in the LBBAP than the BVP group (17.5% ± 10.9% vs 12.3% ± 11.8%; P=0.037), with more than 3-fold increased odds of ER (odds ratio: 4.35; P=0.033). In high sepal scar subgroups (≥5.7%, range: 5.7% to 65.9%), BVP trended towards higher LVEF improvement (9.2% ± 9.4% vs 6.4% ± 12.4%; P=0.085). Interaction between septal scar burden and pacing strategy was significant for ER (P=0.002) and LVEF improvement (P=0.011) after propensity score adjustment. During median follow-up of 33.7 (Q1-Q3: 19.8 to 42.1) months, the composite clinical outcome occurred in 34.7% (n=51) of patients. The high-burden subgroups had worse clinical outcomes independent of CRT method. Remodeling response to LBBAP and BVP among nonischemic cardiomyopathy patients is modified by septal scar burden. High septal scar burden was associated with poor clinical prognosis independent of CRT methods.

Rate of Change in Cardiac Magnetic Resonance Imaging Measures Is Associated With Death in Duchenne Muscular Dystrophy.

Cardiovascular disease is the leading cause of death among patients with Duchenne muscular dystrophy (DMD). Identifying patients at risk of early death could allow for increased monitoring and more intensive therapy. Measures that associate with death could serve as surrogate outcomes in clinical trials. Duchenne muscular dystrophy subjects prospectively enrolled in observational studies were included. Models using generalized least squares were used to assess the difference of cardiac magnetic resonance measurements between deceased and alive subjects. A total of 63 participants underwent multiple cardiac magnetic resonance imaging and were included in the analyses. Twelve subjects (19.1%) died over a median follow-up of 5 years (interquartile range, 3.1-7.0). Rate of decline in left ventricular ejection fraction was faster in deceased than alive subjects (P<0.0001). Rate of increase in indexed left ventricular end-diastolic (P=0.0132) and systolic (P<0.0001) volumes were higher in deceased subjects. Faster worsening in midcircumferential strain was seen in deceased subjects (P=0.049) while no difference in global circumferential strain was seen. The rate of increase in late gadolinium enhancement, base T1, and mid T1 did not differ between groups. Duchenne muscular dystrophy death is associated with the rate of change in left ventricular ejection fraction, midcircumferential strain, and ventricular volumes. Aggressive medical therapy to decrease the rate of progression may improve the mortality rate in this population. A decrease in the rate of progression may serve as a valid surrogate outcome for therapeutic trials.

Operative Morbidity and Mortality of Aortic Stenosis with Left Ventricular Dysfunction

Objectives: Study of the operative morbidity and mortality of aortic stenosis with left ventricular systolic dysfunction (LVEF &lt; or = 35%). Method: 73 patients with a mean age of 55+/-8 years, 59 of whom were men, underwent surgery between January 2014 and december 2019; 14% (10/73) of these patients had a pre-operative low trans-valvular aortic gradient (&lt;30mmHg). We determined the factors predictive of operative mortality using univariate and multivariate analyses, analysed changes in functional status and left ventricular ejection fraction, and compared operative mortality and late survival in these 73 patients with those in a control group with no left ventricular dysfunction. Results: The mean NYHA stage, before and after aortic valve replacement, fell from 3.8 to 1.7, and the mean improvement in LVEF was 28+/-13. In univariate analysis, the parameters significantly associated with operative mortality were arterial hypertension (p=0.039), congestive heart failure (p=0.030), a smaller indexed left ventricular mass (p=0.039), a mean gradient of less than 30mmHg (at the limit of significance (p=0.053)), a low cardiac index (p=0.0045), and mono-truncular coronary involvement (p=0.042). In multivariate analysis, no variable was identified as an independent predictor of operative mortality. Conclusion: Operative mortality was significantly higher 11.7%vs 2.9% (p=0.048) in the group with left ventricular dysfunction, although late survival rates were similar in the 2 groups (86.8% vs 93%). Given the spontaneous prognosis and the increased operative risk, these patients should be operated on.

ASSESSMENT OF SAFETY AND FEASIBILITY OF ROTATIONAL ATHERECTOMY (RA) VERSUS CONVENTIONAL STENTING IN PATIENTS WITH CHRONIC TOTAL OCCLUSION (CTO) LESIONS

Chronic total occlusion (CTO) sores in coronary arteries present a challenge in percutaneous coronary intervention (PCI) because of their complex anatomy and high rates of procedural failure. Objectives: In this comparative study, we aim to investigate the safety and feasibility of rotational atherectomy (RA) versus conventional stenting in patients with chronic total occlusion (CTO) lesions. Methods: This comparative study was conducted at Ayub teaching hospital from September 2023 to December 2023. Data was collected from 110 patients from both genders. Patients aged &gt; 18 years and diagnosed with chronic total occlusion (CTO) lesions in coronary arteries confirmed by coronary angiography were included in the study. Baseline demographic and clinical data, including age, gender, comorbidities, and angiographic characteristics, were collected for each participant. Additionally, procedural details such as the type of intervention, rotational atherectomy, conventional stenting, procedural time, fluoroscopy time, contrast volume, and any adverse events encountered during the procedure were recorded. Results: Data were collected from 110 patients from both genders. The mean age of participants in the Rotational Atherectomy (RA) group was 62.4 ± 7.3 years, while in the Conventional Stenting group, it was 61.8 ± 6.9 years. There were 40 males and 15 females in the RA group, compared to 38 males and 17 females in the Conventional Stenting group. The prevalence of diabetes mellitus was 42.0% in the RA group and 45.5% in the Conventional Stenting group. Left ventricular ejection fraction (LVEF) was 53.7 ± 4.2% in the RA group and 54.1 ± 4.5% in the Conventional Stenting group. The RA group showed a success rate of 81.8%, and the conventional stenting group achieved a success rate of 90.9%. However, the RA group experienced slightly higher rates of major procedural complications (9.1% vs. 5.5%) and minor procedural complications (12.7% vs. 10.9%) than the conventional stenting group. Conventional stenting group, the mean change was -1.2 ± 0.7. Additionally, the incidence of target lesion revascularisation (TLR) was observed in 8 patients (14.5%) in the RA group and 12 patients (21.8%) in the conventional stenting group. Furthermore, major adverse cardiovascular events (MACE) occurred in 9 patients (16.4%) in the RA group and 11 patients (20.0%) in the conventional stenting group. Conclusion: It is concluded that both rotational atherectomy (RA) and conventional stenting are effective and safe treatment options for patients with chronic total occlusion (CTO) lesions. Our findings suggest that both strategies yield comparable procedural success rates, complication rates, and efficacy outcomes, including myocardial infarction frequency, troponin levels, and left ventricular ejection fraction changes.

Mid‐term outcomes of delivery catheter‐based and stylet‐based right ventricular septal pacing: Follow‐up results from a multicenter, prospective, randomized study

AbstractBackgroundThe Mt FUJI study was a multicenter, prospective, randomized, single‐blind, controlled trial comparing delivery catheter‐based and stylet‐based right ventricular (RV) lead placement at the RV septum. This study extended the follow‐up duration to 1 year after implantation.MethodsSeventy patients with pacemaker indications for atrioventricular block were randomly assigned to the delivery catheter and stylet groups. We compared the mid‐term efficacy and safety between the two groups at 1 year after implantation. The primary outcome was the change in the left ventricular ejection fraction (LVEF), and the secondary outcomes were changes in brain natriuretic peptide (BNP) levels, lead parameters, paced QRS duration, and the incidence of adverse events.ResultsAt the 1‐year follow‐up, no significant differences were observed in the changes in the LVEF (+1.0% ± 8.6% vs. +3.1% ± 8.1%, p = .332), BNP levels (+8.0 [−11.1, 26.5] pg/mL vs. −8.7 [−15.3, 13.2] pg/mL, p = .193), or lead performance between the delivery catheter and stylet groups. The QRS duration was significantly shorter in the delivery catheter group than in the stylet group (128 ± 23 ms vs. 146 ± 17 ms, p &lt; .001). All‐cause death, hospitalization for heart failure, new development of atrial fibrillation, and pacing‐induced cardiomyopathy occurred in seven patients in the delivery catheter group and five in the stylet group.ConclusionThe delivery catheter system was similarly useful and safe compared to the stylet system in the mid‐term follow‐up from the Mt FUJI trial. Further long‐term evaluations are warranted.

Abstract 679: TXB-001 is an upgraded conjugated anthracycline that targets tumors with reduced risk of cardiotoxicity, hand-foot syndrome and alopecia

Abstract TXB-001 is a well-optimized N-(2-hydroxypropyl)methacrylamide copolymer-based conjugated pirarubicin (THP) and a novel candidate for developing anticancer drugs. It exhibits tumor-specific accumulation due to the enhanced permeability and retention effects and prolonged circulation time compared with free THP. Its hydrazone bond is dissociated under lower pH conditions, providing selective and rapid release of THP in acidic tumor environments. Therefore, TXB-001 is expected to have high efficacy and low toxicity. Anthracycline anticancer drugs have been widely used for the treatment of several cancers, but their use is limited by several adverse effects (AEs), including cardiotoxicity, which is a life-threatening AE. Furthermore, the maximum lifetime cumulative dose is decided for each anthracycline in clinical use, which leads to discontinuation of the medication. Hand-foot syndrome (HFS) is a dose-limiting AE of DOXIL®, a liposomal formulation of doxorubicin (DOX), and although it is not a life-threatening condition, it significantly deteriorates quality of life (QOL). Alopecia is another common AE, which is relatively noninvasive but adversely affects mental health and reduces QOL. In this study, we confirmed the efficacy of TXB-001 in a mice triple-negative breast cancer (TNBC) model and evaluated the cardiotoxicity-, HFS- and alopecia-inducing effects of TXB-001 in mice and rats to compare the severity with existing anthracycline anticancer drugs, including DOXIL®. The pharmacokinetic (PK) analysis in several tissues, including plasma, tumor, heart, skin of the chest, and palmar and plantar areas, was also performed after a single intravenous administration in rodents. As a result, TXB-001 showed an equivalent or greater antitumor effects than other anthracyclines in the TNBC model, and the AEs were scarcely observed. TXB-001 did not decrease left ventricular ejection fraction, with no or little HFS-like changes compared with DOXIL®, which showed significant histopathological changes. TXB-001 also showed weaker alopecia-inducing effects than DOX, DOXIL®, and THP. In the PK analysis, TXB-001 was distributed in the tumor at a higher concentration than in other tissues, except for plasma. Hence, most of the THP, the active ingredient, was released in the tumor. The exposure of the heart in the TXB-001-treated group was one-tenth of that in the DOXIL®-treated group. Moreover, accumulation in the skin, especially in palmar and plantar areas, was observed for DOXIL®, but no accumulation in the skin was observed for TXB-001. This PK profile consistently demonstrated the antitumor activity of TXB-001, without AEs. TXB-001 reduces the chance of dose-limiting and QOL-threatening AEs, and thus, cancer patients can continue treatment, making it a more convenient anticancer drug in clinical use with a wide safety margin. Citation Format: Keiyu Oshida, Mikito Hirakata, Emi Tomikawa, Chizuka Sakai, Masashi Uchida, Rieko Shimozono, Akiko Izawa, Yoko Koga, Tsubasa Okano, Hideki Narumi, Lisa Munakata, Ryo Suzuki, Miki Nonaka, Yasuhito Uezono. TXB-001 is an upgraded conjugated anthracycline that targets tumors with reduced risk of cardiotoxicity, hand-foot syndrome and alopecia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 679.

Evaluation of Perfusion and Function in Cardiac Radionuclide Imaging in Cases of Heart Failure with Mid-Range Ejection Fraction

Objective: Heart failure with mid-range ejection fraction (HFmrEF) poses a significant clinical challenge due to its diverse etiology and variable prognosis. Patients with HFmrEF exhibit an intermediate level of left ventricular dysfunction, making their management and prognosis less well-defined compared to those with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). Coronary artery disease (CAD) is a common underlying cause of HFmrEF and can further exacerbate myocardial dysfunction under stress conditions. In this study, we aimed to evaluate the change in left ventricular ejection fraction with stress in the presence of coronary artery disease in cases of heart failure with mid-range ejection fraction. Material and Methods: In this retrospective study, we included 507 patients diagnosed with coronary artery disease and an left ventricular ejection fraction (LVEF) of 41-49% measured by echocardiography. All patients underwent a treadmill exercise test using the Bruce protocol, with progressively increasing speed and incline. Myocardial perfusion was assessed using stress gated myocardial perfusion scintigraphy (MPS), and fixed and reversible defects were identified in cases of coronary artery disease. Cardiac scintigraphic images were acquired from the right anterior oblique to the left posterior oblique. We calculated post-stress LVEF and the percentage decrease in LVEF to evaluate cardiac function. Results: Resting LVEF was measured as 46 (43-50), while post-stress LVEF was 35 (25-47) in all patients. Myocardial perfusion was evaluated using stress gated MPS in all patients, with 200 (39.5%) patients showing both fixed and reversible perfusion defects. The rate of decrease in LVEF due to stress was significantly higher in patients with reversible perfusion defects (15.90 (6-30.43) vs. 28.26 (24-43.18), p: 0.0005). Post-stress LVEF was lower in patients with reversible perfusion defects (40 (31-47) vs. 33 (25-38), p: 0.0005). Conclusion: In cases of impaired left ventricular perfusion, quantitative calculations of LVEF may vary, and their reliability may decrease as the ejection fraction decreases under stress conditions. Clinicians should consider this variability in the follow-up of patients with heart failure and mid-range ejection fraction.

The Impact of Intravenous Ferric Carboxymaltose on Reverse Electrical Remodeling Following Cardiac Resynchronization Therapy.

The influence of intravenous ferric carboxymaltose (FCM) on reverse electrical remodeling (RER) in patients with heart failure with reduced ejection fraction (HFrEF) post-cardiac resynchronization therapy (CRT) is unknown. This study examines the effect of iron replacement using intravenous FCM on RER in CRT-implanted HFrEF patients with iron deficiency anemia. We retrospectively analyzed 65 patients with successful CRT-defibrillator between March 2017 and January 2020, all with iron deficiency anemia at implantation. The cohort comprised 35 patients in the FCM group and 30 in the non-FCM group. Follow-up data were obtained from visits 6 months post-CRT implantation including baseline characteristics, echocardiographic left ventricular measurements, and electrocardiograms. Changes in intrinsic QRS duration (iQRS) and left ventricular ejection fraction (LVEF) from baseline to 6 months were assessed. The FCM group showed a greater reduction in iQRS duration compared to the non-FCM group (-10.4 ± 2.2 ms vs. -3 ± 2.9 ms, p < 0.0001). Additionally, at the 6-month follow-up, the increase in LVEF was higher in the FCM group than in the non-FCM group (+3.6 ± 1.6% vs. -0.1 ± 1.7%, p < 0.0001). Correlations were found between changes in ferritin levels and iQRS duration (r = -0.725, p < 0.0001) and LVEF (r = 0.712, p < 0.0001). Multivariate regression analysis revealed that elevated ferritin independently influenced the increase in LVEF (p = 0.006, β = 0.554) and the decrease in iQRS (p < 0.001, β = -0.685). Intravenous iron treatment with FCM may reduce iQRS duration and improve LVEF and functional status in HFrEF patients with iron deficiency anemia following CRT.

Catheter ablation versus medical therapy in atrial fibrillation: an umbrella review of meta-analyses of randomized clinical trials

This umbrella review synthesizes data from 17 meta-analyses investigating the comparative outcomes of catheter ablation (CA) and medical treatment (MT) for atrial fibrillation (AF). Outcomes assessed were mortality, risk of hospitalization, AF recurrence, cardiovascular events, pulmonary vein stenosis, major bleeding, and changes in left ventricular ejection fraction (LVEF) and MLHFQ score. The findings indicate that CA significantly reduces overall mortality and cardiovascular hospitalization with high strength of evidence. The risk of AF recurrence was notably lower with CA, with moderate strength of evidence. Two associations reported an increased risk of pulmonary vein stenosis and major bleeding with CA, supported by high strength of evidence. Improved LVEF and a positive change in MLHFQ were also associated with CA. Among patients with AF and heart failure, CA appears superior to MT for reducing mortality, improving LVEF, and reducing cardiovascular rehospitalizations. In nonspecific populations, CA reduced mortality and improved LVEF but had higher complication rates. Our findings suggest that CA might offer significant benefits in managing AF, particularly in patients with heart failure. However, the risk of complications, including pulmonary vein stenosis and major bleeding, is notable. Further research in understudied populations may help refine these conclusions.

Long-Term Outcomes of Aortic Stenosis Patients with Different Flow/Gradient Patterns Undergoing Transcatheter Aortic Valve Implantation.

Background: Few data exist on the comparative long-term outcomes of severe aortic stenosis (AS) patients with different flow-gradient patterns undergoing transcatheter aortic valve implantation (TAVI). This study sought to evaluate the impact of the pre-TAVI flow-gradient pattern on long-term clinical outcomes after TAVI and assess changes in the left ventricular ejection fraction (LVEF) of different subtypes of AS patients following TAVI. Methods: Consecutive patients with severe AS undergoing TAVI in our institution were screened and prospectively enrolled. Patients were divided into four subgroups according to pre-TAVI flow/gradient pattern: (i) low flow-low gradient (LF-LG): stroke volume indexed (SVi) ≤ 35 mL/m2 and mean gradient (MG) < 40 mmHg); (ii) normal flow-low gradient (NF-LG): SVi > 35 mL/m2 and MG < 40 mmHg; (iii) low flow-high gradient (LF-HG): Svi 35 mL/m2 and MG ≥ 40 mmHg and (iv) normal flow-high gradient (NF-HG): SVi > 35 mL/m2 and MG ≥ 40 mmHg. Transthoracic echocardiography was repeated at 1-year follow-up. Clinical follow-up was obtained at 12 months, and yearly thereafter until 5-year follow-up was complete for all patients. Results: A total of 272 patients with complete echocardiographic and clinical follow-up were included in our analysis. Their mean age was 80 ± 7 years and the majority of patients (N = 138, 50.8%) were women. 62 patients (22.8% of the study population) were distributed in the LF-LG group, 98 patients (36%) were LF-HG patients, 95 patients (34.9%) were NF-HG, and 17 patients (6.3%) were NF-LG. There was a greater prevalence of comorbidities among LF-LG AS patients. One-year all-cause mortality differed significantly between the four subgroups of AS patients (log-rank p: 0.022) and was more prevalent among LF-LG patients (25.8%) compared to LF-HG (11.3%), NF-HG (6.3%) and NF-LG patients (18.8%). At 5-year follow-up, global mortality remained persistently higher among LF-LG patients (64.5%) compared to LF-HG (47.9%), NF-HG (42.9%), and NF-LG patients (58.8%) (log-rank p: 0.029). At multivariable Cox hazard regression analysis, baseline SVi (HR: 0.951, 95% C.I.; 0.918-0.984), the presence of at least moderate tricuspid regurgitation at baseline (HR: 3.091, 95% C.I: 1.645-5.809) and at least moderate paravalvular leak (PVL) post-TAVI (HR: 1.456, 95% C.I.: 1.106-1.792) were significant independent predictors of late global mortality. LF-LG patients and LF-HG patients exhibited a significant increase in LVEF at 1-year follow-up. A lower LVEF (p < 0.001) and a lower Svi (p < 0.001) at baseline were associated with LVEF improvement at 1-year. Conclusions: Patients with LF-LG AS have acceptable 1-year outcomes with significant improvement in LVEF at 1-year follow-up, but exhibit exceedingly high 5-year mortality following TAVI. The presence of low transvalvular flow and at least moderate tricuspid regurgitation at baseline and significant paravalvular leak post-TAVI were associated with poorer long-term outcomes in the entire cohort of AS patients. The presence of a low LVEF or a low SVi predicts LVEF improvement at 1-year.

Evaluation of PHARM‐HF, a pharmacist‐led heart failure medication titration clinic: A pre‐post study

AbstractIntroductionThe PHARM‐HF clinic is a novel, pharmacist‐led medication optimization clinic for patients with heart failure with reduced ejection fraction (HFrEF). PHARM‐HF aims to achieve maximum‐tolerated HFrEF guideline‐directed medical therapy (GDMT) as outlined by the latest Canadian Cardiovascular Society heart failure guidelines.MethodsThis retrospective pre‐post study evaluated consecutive patients attending PHARM‐HF (January 2021–August 2022). The primary outcome was the modified Optimal Medication Therapy (mOMT) score, an aggregate score of HFrEF quadruple therapy. The mOMT score was categorized as suboptimal (score 0–4), acceptable (score 5–7), or optimal (score 8; all four drugs at maximum tolerated dose). Secondary outcomes included change in left ventricular ejection fraction (LVEF) from baseline to 1 year, and Kansas City Cardiomyopathy Questionnaire‐12 (KCCQ; range 0 [worst] to 100 [best]) from baseline to discharge.ResultsOf 81 included patients, median age was 68 years, 21% were female, 61% had New York Heart Association (NYHA) class 2 functional capacity, and median LVEF was 30%. Median mOMT improved from 6 (interquartile range [IQR] 4–7) at baseline to 8 (IQR 7–8) at clinic discharge (p &lt; 0.001; increase from 7% to 73% categorized as optimal). LVEF improved from a median of 30% to 38% at 1 year (p &lt; 0.001). Among 16 patients who completed the KCCQ‐12 at both time points, the score was 62 at baseline and 77 at discharge (p = 0.42).ConclusionsUptake of GDMT significantly increased from admission to discharge from the PHARM‐HF medication optimization clinic, during which other cardiovascular clinicians did not modify HFrEF medications. Furthermore, there was an improvement in LVEF at 1 year. A pilot randomized controlled trial is currently underway to guide the development of a multicenter trial to provide definitive evidence for the role of pharmacist‐led medication optimization in HFrEF.

Inflammation and Fibrosis in Sleep-Disordered Breathing after Acute Myocardial Infarction.

After acute myocardial infarction (AMI), inflammatory processes promote tissue remodeling at the infarct site. Procollagen III amino-terminal propeptide (PIIINP) is a circulating biomarker of type III collagen synthesis that has been shown to be associated with changes in left ventricular ejection fraction (LVEF) and predicts the occurrence of heart failure after AMI. We hypothesize that sleep-disordered breathing (SDB) promotes inflammation and myocardial fibrosis, leading to reduced myocardial salvage. Therefore, in patients with first-time AMI successfully treated with percutaneous coronary intervention (PCI), we aimed to investigate whether circulating levels of high-sensitivity C-reactive protein (hs-CRP) and PIIINP are elevated in patients with SDB compared to patients without SDB. This cross-sectional analysis included a total of 88 eligible patients with first AMI and PCI pooled from two prospective studies and stratified according to the apnea-hypopnea index (AHI, with SDB: AHI ≥ 15 h-1). We analyzed circulating levels of hs-CRP and PIIINP 3-5 days after PCI. Patients with SDB had significantly higher levels of hs-CRP (18.3 mg/L [95% CI, 8.0-42.6] vs. 5.8 mg/L [95% CI, 4.2-19.8], p = 0.002) and PIIINP (0.49 U/mL [95% CI, 0.40-0.60] vs. 0.33 U/mL [95% CI, 0.28-0.43], p < 0.001). In a multivariable linear regression model accounting for important clinical confounders, SDB significantly predicted circulating levels of hs-CRP (p = 0.028). Similarly, only SDB was independently associated with PIIINP (p < 0.001). Only obstructive but not central AHI correlated with circulating levels of hs-CRP (p = 0.012) and PIIINP (p = 0.006) levels. The presence of obstructive SDB after AMI was independently associated with increased circulating levels of hs-CRP and PIIINP. Our results emphasize the important role of SDB as a common comorbidity and indicate increased inflammation and myocardial fibrosis in these patients.

Evaluation of Left Ventricular Hemodynamics with Noninvasive Methods in Cases of Iron Deficiency

Objective: In this study, we aimed to evaluate the effect of iron deficiency on stress ejection fraction by assessing the change in left ventricular ejection fraction during maximum exercise in individuals with iron deficiency. Material and Methods: In this retrospective study, 212 patients, presenting with atypical chest pain and undergoing exercise gated myocardial perfusion scintigraphy, were included. Of the patients, 171 (80.7%) were female, with an average age of 50 (37-59) years. Patients were categorized into two groups: those with iron deficiency and those without. All patients exercised for a minimum of 6 minutes, reaching at least 85% of their maximum heart rate (220 - age). Hemogram, iron binding capacity, and serum ferritin values were recorded for all participants. In our study, SF less than 100 µg/L and TSAT less than 20% were considered low. Results: There was no significant difference in age and gender between the groups with and without iron deficiency (p: 0.758, p: 0.658). Echocardiography-calculated ejection fraction values were 66 (55-72). Rest ejection fraction obtained by force gated myocardial perfusion scintigraphy was 64 (52-70), and post-stress ejection fraction was calculated as 58 (50-69). The rate of decrease in post-stress EF compared to rest EF was calculated as 7.40% (7.81-19.12) in all patients. Echo, rest, and post-stress EF values in group 2 were significantly lower than those in group 1 (p: 0.003, 0.028, 0.0005, respectively). The rate of decrease in post-stress EF between the two groups was significantly higher in group 2 (p: 0.0005). Conclusion: While decreased iron stores and the presence of an iron deficiency state may be well-tolerated during daily activities, maximal exercise can exacerbate the condition if iron deficiency is underlying and undiagnosed. Early diagnosis of iron deficiency, common in society, before the onset of anemia, and prompt treatment are crucial for public health.

Cardiac Structural and Functional Remodeling After Transcatheter Mitral Valve in Valve Implantation: Early Changes and Prognostic Significance

BackgroundTranscatheter mitral valve-in-valve (MViV) replacement has emerged as an alternative to redo mitral valve (MV) surgery for the management of failed bioprosthetic MVs. The degree of cardiac remodeling assessed by echocardiography has been shown to have prognostic implications in degenerative mitral regurgitation patients undergoing MV surgery. The impact of transcatheter MViV in patients with degenerative bioprosthetic MV failure on cardiac remodeling and its associated prognosis remains undescribed. ObjectivesThe aim of this study is to describe the early anatomic and functional changes of the left-sided chambers and right ventricle by echocardiography posttranscatheter MViV intervention and their impact on mortality outcomes. Additionally, we sought to analyze the outcome of heart failure in bioprosthetic MV failure patients undergoing transcatheter MViV replacement. MethodsWe analyzed consecutive patients undergoing MViV intervention for symptomatic bioprosthetic MV failure. Echocardiograms before intervention and within 100 days postintervention were analyzed. A chart review was performed to obtain baseline characteristics, follow-up visits, 30-day heart failure and 1-year all-cause mortality outcomes. ResultsA total of 62 patients (mean age 69 ± 13 years, 61% male) were included in the study. Most patients were undergoing MViV intervention for prosthetic mitral stenosis n = 48 (77.4%) and the rest for mitral regurgitation or mixed disease. Compared with baseline, significant reductions were observed in median left atrial volume (LAV; 103 [81–129] ml vs. 95.2 [74.5–117.5] ml, p < 0.01) and mean (SD) left atrial conduit strain (9.1% ± 5.2% vs. 10.8% ± 4.8%, p = 0.039) within 100 days postintervention. Early reduction in right ventricular free wall global longitudinal strain and fractional area change also occurred postintervention. No significant change in left ventricular chamber dimensions or ejection fraction was observed. During the 1-year follow up period, 5 (8%) patients died. While baseline LAV was not associated with 1-year all-cause mortality (OR 0.98 CI 0.95–1.01; p = 0.27), a change in LAV in the follow up period was associated with all-cause mortality at 1 year (OR 1.06 CI 1.01–1.12; p = 0.023). At 30 days postintervention, 65% of patients had an improvement in their New York Heart Association functional class. ConclusionIn this retrospective study of patients undergoing transcatheter MViV intervention for failed bioprosthetic MVs, early reverse remodeling of the left atrium occurs within 100 days postintervention and reduction in LAV is associated with reduced all-cause mortality at 1 year. In addition, there is significant improvement in heart failure symptoms at 30 days following intervention but further investigation into the longitudinal remodeling changes and long-term outcomes is needed.