Improvement In Ventricular Function Research Articles

Safety and therapeutic potential of allogeneic adipose-derived stem cell spray transplantation in ischemic cardiomyopathy: a phase I clinical trial

BackgroundIschemic cardiomyopathy, characterized by coronary artery atherosclerosis, impairs the myocardial tissue. Coronary artery bypass grafting (CABG) is commonly used to revascularize affected areas and improve patient survival rates; however, it can fail to enhance cardiac function. Impaired capillary blood flow may obstruct functional recovery, prompting interest in treatments, such as angiogenic factor administration. Adipose-derived stem cells (ADSCs), which are known for immune evasion, have shown the potential to construct capillary networks and improve myocardial function. This clinical trial aimed to evaluate the safety and efficacy of ADSC spray therapy combined with CABG.MethodsThis single-center, randomized, double-blind study involved patients with ischemic cardiomyopathy who were scheduled for CABG and who had a left ventricular ejection fraction ≤ 40%. The participants were randomized to receive CABG as well as ADSC spray therapy or placebo. The primary endpoints were safety, changes in late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) volumes, and feasibility. The secondary endpoints included left ventricular function, exercise tolerance, and heart failure symptoms.ResultsSeven patients were enrolled; of them, six were randomized to receive ADSC therapy (n = 3) or placebo (n = 3). The procedure was successfully completed with minimal adverse events. One patient in the ADSC group developed pleural effusion that was resolved with drainage. The LGE-MRI volumes decreased in the ADSC group but remained unchanged in the placebo group. Improvements in left ventricular function and exercise tolerance were noted in the ADSC group, with heart failure symptoms improving to New York Heart Association class I. In contrast, the placebo group showed no significant changes, with one patient experiencing worsening symptoms.ConclusionsADSC spray therapy combined with CABG demonstrated safety and efficacy at enhancing cardiac function. ADSC likely contributes to capillary network reconstruction, thereby augmenting the benefits of CABG. Future phase II and III trials are warranted to confirm its therapeutic efficacy and long-term outcomes. This novel approach represents a significant advancement in the treatment of ischemic cardiomyopathy and offers a viable strategy for improving myocardial function and patient prognosis.Trial registration This study was registered with the Japan Registry of Clinical Trials (jRCT2053190103) and ClinicalTrials.gov (NCT04695522)Graphical

Echocardiographic Evaluation in Cardiac Resynchronization Therapy: A Single Center Experience.

Introduction Heart failure develops as a result of dysfunction in the cardiac muscle, which impairs the heart's ability to pump blood effectively. For this reason, many studies have shown that cardiac resynchronization therapy (CRT) has significantly reduced symptoms and improved cardiac function in patients with heart failure. Echocardiography is crucial in assessing CRT response, as it helps differentiate between patients who benefit from CRT and those who do not by evaluating key parameters like left ventricular ejection fraction (LVEF), a critical parameter in determining CRT eligibility. However, few studies focus specifically on the effectiveness of echocardiography for assessing CRT response, with existing research limited by a lack of standardized protocols and inadequate predictive tools. Accordingly, this study aims to assess the role of echocardiography in evaluating the efficacy of CRT in patients with heart failure at King Faisal Cardiac Center. Methodology This was a retrospective analytical cohort study that included all adult patients diagnosed with heart failure and underwent CRT between January 2017 and December 2021 at King Faisal Cardiac Center, King Abdulaziz Medical City, Jeddah, Saudi Arabia. Data were obtained from the Cardiac Non-invasive Lab, which was selected for its essential diagnostic tools for comprehensive echocardiographic evaluation of CRT efficacy. Study subjects were over 18 years old, diagnosed with heart failure with reduced ejection fraction (LVEF <35%), underwent CRT, and had echocardiograms at baseline and at least six months post-therapy. The collected data were retrieved from electronic medical records (BestCare; ezCaretech Co., Ltd,Seoul, South Korea), including relevant demographics and echocardiographic parameters such as end-systolic volume (ESV), end-diastolic volume (EDV), and ejection fraction (EF). Statistical analysis, paired t-tests,and Shapiro-Wilk test to assess data normality were conducted to evaluate pre- and post-CRT changes, with significance set at P<0.05. Results A total of 53 heart failure patients met the inclusion and exclusion criteria. The results of the study indicate statistically significant differences in the mean EF before and after CRT increased from 29.09±6.52% to 33.3±10.69% (p-value=0.0014). The mean ESV decreased from 114.46±60.63 mL to 97.13±65.89 mL, demonstrating a clinically significant improvement (p=0.056), and the mean EDVdecreased from 157.08±64.67 mL to 138.87±78.07 mL (p = 0.0158). Furthermore, the EF increased by 14.47%, and the ESV decreased by 15.14% after CRT.These findings indicate improvement in left ventricular function following CRT. Conclusion The study demonstrates significant improvements in echocardiographic parameters based on echocardiogram findings, particularly the outcomes of EF and ESV after CRT in patients with heart failure with reduced ejection fraction.These findings highlight the potential of CRT as an effective therapy and aid in detecting responders to treatment. Nevertheless, the study is limited by a relatively small sample size, exclusion of comorbidities, and short follow-up period. Therefore, further longitudinal studies with larger cohorts and consideration of comorbidities are recommended.

Seguimiento Ecocardiográfico De Cambios Anatómicos Del Miocardio De Pacientes Pediátricos con Diagnóstico De Miocardiopatía No Compactada. 2017 – 2021

Background: Non-compaction cardiomyopathy (NCM) is known as the lack of maturation of the myocardium that is evidenced by prominent trabeculations and the presence of recesses in newborns and infants that can manifest clinically as heart failure. The purpose of the research is to evaluate the anatomical development of pediatric patients diagnosed with NCM at an early age. Clinical Case: Retrospective case series study of patients diagnosed with non-compaction cardiomyopathy during the first year of life, confirmed according to Jenni criteria, with echocardiographic follow-up every 6 months, from 2017 - 2021. The patients were diagnosed in the first months of life. life, 3 had associated heart disease, 3 had arrhythmias, 3 died and 1 abandoned the controls at 2 months of age. In the 3 patients who remained, it was evident that the ratio of non-compacted myocardium (NC) / compacted myocardium (C) only remained high in 1 patient. The ejection fraction (EF) improved in all patients, the number of trabeculae only decreased in one patient. Conclusions: Anatomical changes in patients diagnosed with non-compaction cardiomyopathy can evolve to myocardial maturation and improvement in ventricular function.

Comparison of pulsed field ablation versus cryoballon and radiofrequency ablation for pulmonary vein isolation in atrial fibrillation patients with heart failure

Abstract Background Pulmonary vein isolation (PVI) is the gold standard for atrial fibrillation (AF) ablation and can be achieved by a variety of technical methodes. While thermal ablation modalities (TA), such as cryoballon (CB) and radiofrequency ablation (RF) have been established as the standard approaches, PFA has been introduced as a nvel non-thermal modality showing comparable safety and procedural efficiency. Despite the high incidence of AF in heart failure (HF) patients, data comparing outcomes of HF patients undergoing PVI by either PFA or thermal ablation (RFA/CB) are limited. Purpose This study’s aim was to compare the efficacy and safety of PFA for AF ablation versus CB/RFA in HF patients. Methods Consecutive HF patients with preserved (HFpEF), mildly reduced (HFmrEF) and reduced (HFrEF) ejection fraction undergoing PVI for AF by either PFA or CB/RFA at our institution were included. The primary end-point was time to death or recurrence of AF. Secondary end-points were periprocedural complications and clinical and echocardiographic parameters. Results We included 140 HF patients who underwent PVI either by PFA (PFA group, 76 patients) or thermal ablation approaches (TA group, 64 patients). Our patients had a mean age of 69 years and were predominantly male (62%). There was no significant difference in the baseline characteristics and in the type of AF between both groups (42% with ParAF, 45% with PersAF) and 13% LSPersAF). The distribution of heart failure types was similar between both groups: HFpEF (PFA: 71%, TA: 75%), HFmrEF (PFA: 21%, TA: 20%) and HFrEF (PFA: 8 %, TA: 5%). After the 365-days follow-up period we observed no significant difference for the primary end-point between both groups (HR: 0.79, 95% CI 0.35-1.78; p=0.575). In total 58% of the PFA patients and 59% of the TA group were still free from AF. While symptom improvement was documented in both groups, patients in the PFA group showed significant improvement of left atrial volume index (p = 0.014), NT-pro BNP levels (p = 0.046), and left ventricular ejection fraction (LVEF) (p = 0.005). Conclusion In this study, PFA and thermal ablation modalities showed comparable results in terms of safety and procedural efficiency in patients with heart failure. Since previous studies have shown that HF patients with AF benefit from PVI using thermal ablation modalities, our results suggest that PFA might also be a promising ablation method in this vulnerable population, inducing left atrial reverse remodeling and thereby contributing to improvement of left ventricular systolic function.

Baroreflex activation therapy in heart failure patients with reduced ejection fraction: a long-term follow up

Abstract Introduction Heart failure with reduced ejection fraction (HFrEF) is a major public health concern with substantial morbidity and mortality. Overactivation of the sympathetic nervous system is a key pathophysiological process driving heart failure progression. Baroreceptor activation therapy (BAT) targets this autonomic imbalance and is a promising treatment strategy for patients with HFrEF. Current short-term studies indicate that BAT provides symptomatic relief, improvement in left ventricular function and cardiac biomarkers. However, data regarding the long-term effect of BAT on HFrEF are scarce. Purpose This study aims to assess long-term outcome in HFrEF patients who underwent BAT. Methods Patients with HFrEF who received BAT between 2014-2023 were followed until latest available follow-up. Symptom burden, echocardiography and laboratory testing were assessed before BAT implantation and in subsequent follow ups. Results 23 patients (mean age 66±10 years, 83% men) with HFrEF were included in the study. Etiology of heart failure was ischemic in 70%. The majority of patients (96%) suffered from NYHA III with a mean left ventricular ejection fraction (LVEF) of 23±8% and NTproBNP of 2463±2922pg/ml. Complication occurred in one patient during BAT implantation (4%). Mean follow-up was 3±2 (max. 7.5) years. BAT reduced NYHA classification in 12 patients (52%) after 1 year, of which 1 patient remained in ameliorated NYHA for 7.5 years. Evolution of NYHA functional class over time is shown in Figure 1. Echocardiographic evaluation revealed significant improvement in LVEF of 9±9% after 1 year (p&amp;lt;0.001) and by 11±9% after 2 years (p=0.005). In long-term a trend towards improved LVEF could be observed (Figure 2). In addition, BAT mildly reduced NTproBNP in the first 2 years (after 1 year non-significantly by -396±1006pg/ml and significantly after 2 years by -566±651pg/ml (p=0.039)). Seven patients reaching recommended replacement time underwent device exchange. Four patients deceased during observation time. Conclusion BAT resulted in a substantial reduction in NYHA classification, improvement in LVEF, and a delayed reduction in NTproBNP levels. These findings highlight the long-term efficacy and potential benefits of BAT as a therapeutic intervention for patients with HFrEF.Sankey plot of NYHA class over timeAlteration of LVEF over time

Cardiac sympathetic innervation, assessed with 123I-MIBG SPECT, predicts left ventricular function improvement in patients with newly diagnosed dilated cardiomyopathy

Abstract Introduction Beta-blockers (BB) are commonly prescribed medications for heart failure (HF) due to their ability to counteract the increased sympathetic nervous system (SNS) activity seen in HF, resulting in downregulation and desensitization of β-receptors. In patients with dilated cardiomyopathy (DCM), the introduction of BB therapy can lead to left ventricular ejection fraction (LVEF) improvement in 30-50% of cases. Single-photon emission computed tomography (SPECT) with 123I-meta-iodobenzylguanidine (MIBG) is a useful tool for assessing cardiac SNS activity. Healthy individuals typically exhibit high SPECT-MIBG uptake and low washout rate (WR) due to normal β-receptor levels and low norepinephrine (NE) levels, respectively (Fig 1A). While better SPECT-MIBG results have been associated with LVEF improvement in the general HF population, less data is available for DCM patients. Purpose This study aimed to evaluate the predictive value of MIBG-SPECT for LVEF improvement in newly diagnosed DCM patients. Methods Twenty-one DCM patients (mean age 47 ± 10 years, 90% male, baseline LVEF 29.5 ± 8.7%, left ventricular end-diastolic volume (LVEDV) 114 ± 36 ml/m2) with stable HF symptoms (NYHA class 1.8 ± 0.6) and newly diagnosed DCM underwent baseline MIBG-SPECT and echocardiography. HF therapy was initiated and up-titrated, and echocardiography was repeated at 6 months. Semi-quantitative parameters from MIBG-SPECT, including the MIBG uptake ratio from the heart and mediastinum (H/M) at 15 minutes (-15) and 4 hours (-4), as well as the WR [WR = (H/M-15 - H/M-4) / H/M-15], were evaluated. Patients were stratified based on median WR - 8.79 (IQR 5.17-12.90). Results After 6-months of HF therapy up-titration, 18 patients improved LVEF, and the mean LVEF increase was 7.7 ± 10.4%. Although, patients with WR &amp;gt; median did not differ in terms of baseline LVEF (30.2 ± 7.0 vs. 27.7 ± 9.6, p=0.52), they had worse LVEF at 6 months (32.0 ± 11.0 vs. 40.6 ± 9.2%, p=0.04). Moreover, WR at baseline strongly correlated with 6-month LVEF (R=-0.51, p=0.01) and was a significant predictor of 6-month LVEF (β=-0.55 ± 0.19, p=0.009). Moreover, WR could successfully predict LVEF improvement ≥ 10% (OR 1.27 [95%CI 1.01-1.61], p=0.03; AUC 0.82 [95%CI 0.63-0.99], p&amp;lt;0.001) with a cut-off point of 8.0 (sensitivity 88%, specificity 77%) (Fig 1B). Conclusion Most DCM patients demonstrated LVEF improvement during 6 months of HF therapy up-titration. Baseline WR from MIBG-SPECT was found to be a reliable predictor of significant LVEF improvement in this patient population.Fig1.A-SPECT-MIBG results. B-ROC curve.

Baroreflex activation therapy in advanced heart failure: A long-term follow-up.

Baroreceptor activation therapy (BAT) is a promising new treatment strategy for patients with heart failure with reduced ejection fraction (HFrEF). It provides symptomatic relief, improvement in left ventricular function and reduction of cardiac biomarkers. Data regarding the long-term effect of BAT on HFrEF are scarce. This retrospective, monocentric study aimed to assess long-term outcome in patients who underwent BAT. Patients with HFrEF who received BAT at Hannover Medical School between 2014 and 2023 were followed until the latest available follow-up. Symptom burden, echocardiography and laboratory testing were assessed before BAT implantation and in subsequent follow-ups. Twenty-three patients (mean age 66±10years, 83% male) with HFrEF were included in the study. Aetiology of heart failure was ischaemic in 70%. The majority of patients (96%) suffered from New York Heart Association (NYHA) III with a mean left ventricular ejection fraction (LVEF) of 23±8% and N-terminal pro-B-type natriuretic peptide (NT-proBNP) of 2463±2922pg/mL. A complication occurred in one patient during BAT implantation (4%). The mean follow-up was 3±2 (max. 7.5) years. BAT reduced NYHA classification in 12 patients (52%) after 1year, of which one patient remained in ameliorated NYHA for 7.5years. Echocardiographic evaluation revealed significant improvement in LVEF by 9±9% after 1year (P<0.001) and by 11±9% (P=0.005) after 2years. In addition, BAT mildly reduced NT-proBNP in the first 2years [non-significantly after 1year by 396±1006pg/mL and significantly after 2years by 566±651pg/mL (P=0.039)]. Seven patients reaching the recommended replacement time underwent device exchange. Four patients died during observation time. BAT resulted in a substantial reduction in NYHA classification and improvement in LVEF that lasted over long-term follow-up in many patients. NT-proBNP level decreased interim in long-term follow-up. These findings highlight the long-term efficacy and potential benefits of BAT as a therapeutic intervention for patients with HFrEF.

Circulating Cell-Free Nuclear DNA Predicted an Improvement of Systolic Left Ventricular Function in Individuals with Chronic Heart Failure with Reduced Ejection Fraction

Background: Patients with heart failure (HF) with improved ejection fraction (HFimpEF) demonstrate better clinical outcomes when compared with individuals without restoration of cardiac function. The identification of predictors for HFimpEF may play a crucial role in the individual management of HF with reduced ejection fraction (HFrEF). Cell-free nuclear (cf-nDNA) DNA is released from damaged cells and contributes to impaired cardiac structure and function and inflammation. The purpose of the study was to elucidate whether cf-nDNA is associated with HFimpEF. Methods: The study prescreened 1416 patients with HF using a local database. Between October 2021 and August 2022, we included 452 patients with chronic HFrEF after prescription of optimal guideline-based therapy and identified 177 HFimpEF individuals. Circulating biomarkers were measured at baseline and after 6 months. Detection of cf-nDNA was executed with real-time quantitative PCR (qPCR) using NADH dehydrogenase, ND2, and beta-2-microglobulin. Results: We found that HFimpEF was associated with a significant decrease in the levels of cf-nDNA when compared with the patients from persistent HFrEF cohort. The presence of ischemia-induced cardiomyopathy (odds ration [OR] = 0.75; p = 0.044), type 2 diabetes mellitus (OR = 0.77; p = 0.042), and digoxin administration (OR = 0.85; p = 0.042) were negative factors for HFimpEF, whereas NT-proBNP ≤ 1940 pmol/mL (OR = 1.42, p = 0.001), relative decrease in NT-proBNP levels (&gt;35% vs. ≤35%) from baseline (OR = 1.52; p = 0.001), and cf-nDNA ≤ 7.5 μmol/L (OR = 1.56; p = 0.001) were positive predictors for HFimpEF. Conclusions: We established that the levels of cf-nDNA ≤ 7.5 μmol/L independently predicted HFimpEF and improved the discriminative ability of ischemia-induced cardiomyopathy, IV NYHA class, and single-measured NT-proBNP and led to a relative decrease in NT-proBNP levels ≤35% from baseline in individuals with HFrEF.

A comparative study on the effect of coronary angioplasty on left ventricular function in post myocardial infarction among patients with and without type-2 diabetes mellitus

Background and objectives. Coronary angioplasty is a common intervention for improving cardiac function postmyocardial infarction. However, the impact of this procedure in patients with type-2 diabetes mellitus (T2DM) compared to those without diabetes remains less understood. Material and methods. This study included 50 patients who underwent coronary angioplasty post-myocardial infarction. Patients were divided into two groups based on the presence (Group A) or absence (Group B) of T2DM, with 6 patients in each group. We assessed left ventricular function using echocardiography, focusing on ejection fraction and wall motion score, at baseline, and at 1, 3, and 6 months post-angioplasty. Additional data on clinical outcomes, functional status, cardiac biomarkers, medication use, comorbid condition management, and hemodynamic measurements were also collected. Results. Both groups showed improvement in left ventricular function post-angioplasty, with no significant difference in ejection fraction and wall motion score between the two groups at each follow-up. Clinical outcomes, functional status, and biomarker levels were comparable between groups. Medication compliance was high in both groups. The control of comorbid conditions and hemodynamic stability post-angioplasty were similarly maintained in both diabetic and nondiabetic patients. Conclusion. Coronary angioplasty positively impacts left ventricular function in post-myocardial infarction patients, irrespective of the presence of T2DM. Both diabetic and non-diabetic patients demonstrated similar improvements in cardiac function and overall clinical outcomes, suggesting that angioplasty is an effective intervention for post-myocardial infarction patients regardless of their diabetes status. Further studies with larger sample sizes are recommended to validate these findings.

IMPROVEMENT IN LV END-DIASTOLIC PRESSURE AFTER PRIMARY PCI AND ITS IMPACT ON PATIENTS’ RECOVERY

Left ventricular end-diastolic pressure (LVEDP) is a crucial indicator of cardiac function, particularly in patients with acute ST-segment elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (PCI) is the standard of care for STEMI, but its impact on LVEDP and patient recovery remains to be thoroughly studied. Objective: This study aimed to evaluate the improvement in LVEDP following primary PCI in patients with acute STEMI and to assess its impact on recovery and clinical outcomes. Methods: This prospective study included 100 patients with acute STEMI treated by primary PCI. LVEDP was recorded at four-time points: before PCI, and at one week, one month, and three months post-PCI. Demographic and clinical characteristics were also collected. Statistical analysis was performed to compare LVEDP values at different time intervals using paired t-tests and repeated measures ANOVA to assess significant changes over time. Results: The mean LVEDP significantly decreased from 18 ± 4 mmHg before PCI to 12 ± 3 mmHg at one week, 10 ± 2 mmHg at one month, and 9 ± 2 mmHg at three months post-PCI (p &lt; 0.001). This demonstrated a consistent improvement in left ventricular function and hemodynamic status, suggesting favorable patient recovery post-intervention. Conclusion: Primary PCI significantly reduces LVEDP in patients with acute STEMI, leading to improved cardiac function and patient recovery. Monitoring LVEDP post-PCI can serve as a valuable predictor of patient prognosis and long-term outcomes. Further studies are warranted to explore additional therapies that may further enhance recovery and improve the quality of life in STEMI patients.

Cardiac decompression and right ventricular function improvement after bar removal in patients with pectus excavatum.

Pectus excavatum, the most frequent malformation of the chest wall, has been related to cardiac compression and exercise intolerance. Cardiac outcomes after minimally invasive repair of pectus excavatum with retrosternal implants, particularly after removal (> 2 years postoperative) are generally unknown. We evaluated stress echocardiography outcomes before repair and after bar removal. This study comprised a retrospective cohort of patients with diagnosis of isolated pectus excavatum who underwent stress echocardiography before minimally invasive repair with retrosternal implants, and after bar removal. The diastolic function was evaluated by means of the trans tricuspid flow and tissue doppler imaging. The compression of the atrioventricular groove was assessed using the trans tricuspid gradient and the tricuspid area. We included 43 patients, with a mean age of 15.7 ± 4.0 years (91% male). After bar removal, 83% of patients referred improvement of exercise capacity. Furthermore, we found a significant improvement in right ventricular filling patterns, including a better E/A ratio profile during exercise (p = 0.001), lower filling pressures both at rest (p < 0.0001) and during exercise (p = 0.031), and lower rates of resting paradoxical septal motion [70% vs. 20%, p = 0.0007]. The trans tricuspid mean gradient during exercise was significantly lower after bar removal (p < 0.0001). In this study involving patients with minimally invasive repair of pectus excavatum, we demonstrated a beneficial impact of such intervention after bar removal, with significant improvements related to the right ventricular function, as well as signs of relief of cardiac compression.

Endovascular Treatment of Flow-Limiting Iliofemoral Stenosis Improves Left Ventricular Diastolic Function in Patients With HFpEF by Reducing Aortic Pulsatile Load.

Recent research indicates that there is a high prevalence of heart failure with preserved ejection fraction in patients with peripheral artery disease. We hypothesized that endovascular treatment (EVT) of flow-limiting peripheral stenosis improves left ventricular (LV) diastolic function. Thirty patients with symptomatic peripheral artery disease and heart failure with preserved ejection fraction according to Heart Failure Association-preserved ejection fraction score who were scheduled for EVT or angiography were investigated at baseline, the day after EVT (n=25) or angiography (control, n=5), and at 4 months follow-up. Peripheral hemodynamics were determined by the total peripheral resistance, common femoral artery flow, and ankle brachial index. Aortic function was measured by arterial compliance, augmentation index, and pulse wave velocity. Aortic pulsatile load was estimated as the characteristic impedance of the proximal aorta and the magnitude of wave reflection (reflection coefficient). LV mass index, LV mean wall thickness, and systolic and diastolic function were assessed using echocardiography. Patient-centered outcomes were treadmill walking distance and New York Heart Association class. After EVT, peripheral hemodynamics changed significantly with a decrease in total peripheral resistance and an increase in common femoral artery flow and ankle brachial index. Aortic function improved after EVT, with significantly reduced augmentation index and pulse wave velocity and increased compliance immediately and at follow-up, resulting in a reduction in aortic pulsatile load (characteristic impedance of the proximal aorta and reflection coefficient). Concurrently, LV diastolic function improved after EVT compared with control, acutely and at follow-up, with increased septal and lateral e´ velocities and decreased E/e´ and left atrial volume index. The LV mass index and LV mean wall thickness decreased at follow-up. The New York Heart Association class and treadmill walking distance improved post-EVT at follow-up. Augmentation index, pulse wave velocity, and arterial compliance were identified as independent contributors to E/e´. Endovascular treatment of flow-limiting iliofemoral stenosis reduces aortic pulsatile load and concurrently lowers total peripheral resistance. This beneficial effect is associated with an acute and sustained improvement of left ventricular diastolic function. URL: http://www.clinicaltrials.gov; Unique identifier: NCT02728479.

Effect of a polyherbal Unani formulation on left ventricular diastolic dysfunction in hypertensive patients- a randomized single blind placebo controlled clinical trial.

Diastolic dysfunction represents an important pathophysiological intermediate between hypertension and heart failure. In the last two decades, the prevalence of heart failure patients having normal or near normal ejection fraction (EF) has increased to around 60 %. It thus poses a great morbidity and mortality risk to the population. In view of present scenario of high prevalence, lack of evidence-based therapy, and limited clinical trials, this study aimed to evaluate how a Unani formulation affects the improvement of the left ventricular diastolic function. This clinical trial was set up as a randomized, placebo-controlled study involving 35 participants, with 18 individuals in the test group and 17 in the control group. Test group received 3.5 g of a polyherbal Unani formulation in capsule form along with 35 mL of an extract of Borago officinalis L. (Arq-e-Gaozaban), divided into two doses after meals. Meanwhile, the control group received a placebo in the same manner over an eight-week period. Follow-ups were conducted every 15days to assess both subjective and objective parameters in all participants. The test formulation shows significant improvement in dyspnea and diastolic function from baseline to the end of trial (p<0.05), slight improvement in palpitations (p>0.05) and highly significant improvement in easy fatigability (p=0.001) as compared to the control. The present study shows the effectiveness of the test drug in enhancing the diastolic function of left ventricle and alleviating other symptoms associated with ventricular diastolic dysfunction. Nevertheless, additional research with longer follow-up durations is necessary to clarify its efficacy and establish optimal treatment approaches for ventricular diastolic dysfunction in Unani medicine.

Abstract Mo029: Angiotensin Receptor Neprilysin Inhibitor improves cardiac hemodynamics and arrhythmogenesis in mitral regurgitation-induced heart failure—from bench to bedside approach

Background: An effective pharmacological therapy yet exists to mitigate mitral regurgitation (MR) progression before surgical interventions. Angiotensin receptor-neprilysin inhibitor (ARNI) has shown benefits in patients with heart failure (HF) with reduced ejection fraction but whether it can reduce degenerative MR induced HF remains unknown. Aim: To test the efficacy of ARNI in improving cardiac function in degenerative MR -induced HF. Methods and Results: Using a novel rat model of degenerative MR, we found that in degenerative MR rats treated with ARNI, left ventricular function and atrial fibrillation (AF) inducibility significantly improved compared with those treated with valsartan only (fractional shortening 61.78±7.26% v.s. 55.07±6.63%). Also, the AF inducibility dropped from 83% to 25% in MR rats treated with ARNI than to 58.3% in those treated with valsartan. ARNI treatment demonstrated significant attenuation of fibrosis, apoptosis and expressions of endoplasmic reticulum (ER) stress and inflammatory-associated proteins in left ventricular tissues compared to valsartan. In a shear stress model, the treatment of ARNI on cardiomyocytes mitigated the flow triggered activities of both ER released calcium signaling and store-operated calcium entry. Parallelly, we prospectively included 65 patients with degenerative MR receiving valsartan or ARNI and followed Holter electrocardiography and echocardiography. Notably, compared with degenerative MR patients receiving valsartan, those prescribed with ARNI demonstrated significant improvement of AF burden and left ventricular function. Conclusions: Degenerative MR-induced cardiovascular dysfunction including fibrosis and ER stress, were more effectively attenuated by ARNI treatment than by valsartan alone.

Insuficiencia cardiaca con fracción de eyección del ventriculo izquierdo recuperada. Reporte de caso

Heart failure with recovered ejection fraction is defined as the improvement of left ventricular systolic function (LVEF) to values ≥ 40%, after having presented a reduced LVEF (&lt; 40%) at a previous time and ≥10% absolute improvement in LVEF. It is a chronic and dynamic condition with a high risk of relapse and deterioration, so close monitoring and optimal medical therapy are essential for its management. A case is presented of a young male patient with dilated cardiomyopathy with severe left ventricular systolic dysfunction, who with neurohormonal therapy for heart failure, showed rapid clinical recovery and improvement of ejection fraction and left ventricular remodeling. Further studies are needed to better understand this condition and its long-term treatment.

Metabolomics of repetitive myocardial stunning in chronic multivessel coronary artery stenosis: Effect of non-selective and selective β1-receptor blockers.

Chronic coronary artery stenosis can lead to regional myocardial dysfunction in the absence of myocardial infarction by repetitive stunning, hibernation or both. The molecular mechanisms underlying repetitive stunning-associated myocardial dysfunction are not clear. We used non-targeted metabolomics to elucidate responses to chronically stunned myocardium in a canine model with and without β-adrenergic blockade treatment. After development of left ventricular systolic dysfunction induced by ameroid constrictors on the coronary arteries, animals were randomized to 3months of placebo, metoprolol or carvedilol. We compared these two β-blockers with their different β-adrenergic selectivities on myocardial function, perfusion and metabolic pathways involved in tissue undergoing chronic stunning. Control animals underwent sham surgery. Dysfunction in stunned myocardium was associated with reduced fatty acid oxidation and enhanced ketogenic amino acid metabolism, together with alterations in mitochondrial membrane phospholipid composition. These changes were consistent with impaired mitochondrial function and were linked to reduced nitric oxide and peroxisome proliferator-activated receptor signalling, resulting in a decline in adenosine monophosphate-activated protein kinase. Mitochondrial changes were ameliorated by carvedilol more than metoprolol, and improvement was linked to nitric oxide and possibly hydrogen sulphide signalling. In summary, repetitive myocardial stunning commonly seen in chronic multivessel coronary artery disease is associated with adverse metabolic remodelling linked to mitochondrial dysfunction and specific signalling pathways. These changes are reversed by β-blockers, with the non-selective inhibitor having a more favourable impact. This is the first investigation to demonstrate that β-blockade-associated improvement of ventricular function in chronic myocardial stunning is associated with restoration of mitochondrial function. KEY POINTS: The mechanisms responsible for the metabolic changes associated with repetitive myocardial stunning seen in chronic multivessel coronary artery disease have not been fully investigated. In a canine model of repetitive myocardial stunning, we showed that carvedilol, a non-selective β-receptor blocker, ameliorated adverse metabolic remodelling compared to metoprolol, a selective β1-receptor blocker, by improving nitric oxide synthase and adenosine monophosphate protein kinase function, enhancing calcium/calmodulin-dependent protein kinase, probably increasing hydrogen sulphide, and suppressing cyclic-adenosine monophosphate signalling. Mitochondrial fatty acid oxidation alterations were ameliorated by carvedilol to a larger extent than metoprolol; this improvement was linked to nitric oxide and possibly hydrogen sulphide signalling. Both β-blockers improved the cardiac energy imbalance by reducing metabolites in ketogenic amino acid and nucleotide metabolism. These results elucidated why metabolic remodelling with carvedilol is preferable to metoprolol when treating chronic ischaemic left ventricular systolic dysfunction caused by repetitive myocardial stunning.

Therapy duration and improvement of ventricular function in de novo heart failure: the Heart Failure Optimization study.

In patients with de novo heart failure with reduced ejection fraction (HFrEF), improvement of left ventricular ejection fraction (LVEF) is expected to occur when started on guideline-recommended medical therapy. However, improvement may not be completed within 90 days. Patients with HFrEF and LVEF ≤ 35% prescribed a wearable cardioverter-defibrillator between 2017 and 2022 from 68 sites were enrolled, starting with a registry phase for 3 months and followed by a study phase up to 1 year. The primary endpoints were LVEF improvement > 35% between Days 90 and 180 following guideline-recommended medical therapy initiation and the percentage of target dose reached at Days 90 and 180. A total of 598 patients with de novo HFrEF [59 years (interquartile range 51-68), 27% female] entered the study phase. During the first 180 days, a significant increase in dosage of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists was observed (P < .001). At Day 90, 46% [95% confidence interval (CI) 41%-50%] of study phase patients had LVEF improvement > 35%; 46% (95% CI 40%-52%) of those with persistently low LVEF at Day 90 had LVEF improvement > 35% by Day 180, increasing the total rate of improvement > 35% to 68% (95% CI 63%-72%). In 392 patients followed for 360 days, improvement > 35% was observed in 77% (95% CI 72%-81%) of the patients. Until Day 90, sustained ventricular tachyarrhythmias were observed in 24 wearable cardioverter-defibrillator carriers (1.8%). After 90 days, no sustained ventricular tachyarrhythmia occurred in wearable cardioverter-defibrillator carriers. Continuous optimization of guideline-recommended medical therapy for at least 180 days in HFrEF is associated with additional LVEF improvement > 35%, allowing for better decision-making regarding preventive implantable cardioverter-defibrillator therapy.

Predictors of long-term success after successful explantation of continuous flow left ventricular assist device support.

Predictors and evaluations of continuous flow left ventricular assist device (cf-LVAD) explantation in recovered patients remains under discussion due to lack of evidence on long-term safety and efficacy. This study summarized our experiences regarding cf-LVAD explantation in non-ischaemic dilated cardiomyopathy patients and estimated a predictor for sufficient myocardial recovery allowing LVAD explant. We retrospectively identified 135 adult patients with cf-LVAD therapy as bridge to heart transplant due to non-ischaemic dilated cardiomyopathy. Of those, 13 patients underwent device explantation (recovery group) after myocardial recovery. 12 (92%) of the explanted patients were evaluated using our weaning protocol, and underwent surgical explantation. Meanwhile, the remaining 122 continued with cf-LVAD therapy (non- recovery group). Multivariate logistic regression analysis revealed time interval between the first heart failure event and cf-LVAD implantation as an independent predictor for successful explantation. The optimal time interval cutoff value to predict cf-LVAD explantation was 7 months, with a sensitivity of 91.0% and specificity of 84.6%. Echocardiography in patients with successful cf-LVAD explantation showed significant improvement of left ventricular function and dimensions at six months postoperatively. The 13 explanted patients are currently alive at a median of 30 (IQR; 18-58) months after explantation. The survival rate free from rehospitalization due to heart failure following explantation was 100%. Left ventricular function and remodelling after explantation were also preserved. In non-ischaemic dilated cardiomyopathy patients with a short interval between the first heart failure event and cf-LVAD therapy, left ventricular myocardium may recover in an early phase after device implantation.

Life-threatening constrictive pericarditis accompanied by synthetic cannabinoid use: A case report and literature review

Rationale: Synthetic cannabinoids are increasingly used as recreational drugs and have been associated with adverse cardiovascular effects. However, reports of synthetic cannabinoids accompanied by constrictive pericarditis are limited. Patient’s concern: A 28-year-old male with a history of synthetic cannabinoid (Bonzai) abuse presented with chest discomfort, dyspnea, and lower extremity edema. Investigations revealed reduced left ventricular ejection fraction, elevated inflammatory markers, low electrocardiogram voltages, and atrial fibrillation. Diagnosis: Chest spiral computerized tomography scan and chest X-ray demonstrated pericardial calcification. Cardiac magnetic resonance imaging and right heart catheterization were done to confirm the possibility of constrictive pericarditis. Based on the patient’s addiction history and exclusion of rheumatologic and infectious causes, it was supposed that constrictive pericarditis and cardiomyopathy may be accompanied by synthetic cannabinoid use. Interventions: The patient received standard medical therapy, including loop diuretics for cardiomyopathy and constrictive pericarditis. Catheter ablation was recommended for his rhythm control, and he was planned for close monitoring of clinical and echocardiographic response and evaluation of the need for surgical pericardiectomy in the future. Outcomes: After 6 months follow-up, echocardiographic exam revealed no significant improvement in ventricular function. However, due to the high surgical risk, the patient’s poor compliance, and the continuation of drug abuse, he was not a good candidate for surgery according to our heart team’s decision. Lessons: Synthetic cannabinoids can trigger constrictive pericarditis, and clinicians should consider them when evaluating patients with compatible symptoms and exposure history. Further research on the cardiovascular effects of synthetic cannabinoids is needed and public education on potential harms is warranted.

Outcomes with physiologic His bundle pacing in patients with narrow QRS complex

BackgroundIn patients with narrow QRS complex, both ventricular and biventricular pacing is associated with increased cardiac morbidity and mortality. This risk is not decreased by ventricular pacing avoidance algorithms, which cause nonphysiologic atrioventricular (AV) delays. ObjectiveThis study aimed to report outcomes in patients with narrow QRS complex when the paced complex is in normal range and physiologic AV delays are programmed. MethodsIn 196 patients with QRS duration of 92 ± 10 ms, permanent pacing was done at the site of the His bundle electrogram. The pacemakers were then programmed to maintain physiologic AV delays and to increase heart rates in response to exercise. Patients received usual care and were observed for 3 years. ResultsThe paced complex exhibited a delta wave, and the ventricular activation time, QRS axis, and lead I voltage remained in normal range. Physiologic programming resulted in His bundle pacing burden of 92%. In patients with decreased ejection fraction, there was significant improvement in left ventricular function, left ventricular dilation, and mitral regurgitation (P < .003). In patients with normal ejection fraction, left ventricular function remained normal without new valvular abnormalities. The 3-year all-cause mortality was 10%, and there was no increase in heart failure admissions. ConclusionIn patients with narrow QRS complex, when paced QRS morphology is maintained in normal range and AV dyssynchrony is avoided, His bundle pacing is associated with low all-cause mortality and improvement in abnormal echocardiographic parameters. The paced QRS morphology and physiologic AV delays may be important factors to evaluate in future trials of conduction system pacing.