Reverse Cardiac Remodeling Research Articles

Design of the remedē System Therapy (rēST) study: A prospective non-randomized post-market study collecting clinical data on safety and effectiveness of the remedē system for the treatment of central sleep apnea

BackgroundCentral sleep apnea (CSA) is a disorder defined by lack of respiratory drive from the brain stem on breathing efforts. There is a lack of established therapies for CSA and most available therapies are limited by poor patient adherence, limited randomized controlled studies, and potentially adverse cardiovascular effects. The remedē System (ZOLL Respicardia, Inc., Minnetonka, Minnesota) uses transvenous phrenic nerve stimulation to stimulate the diaphragm, thereby restoring a more normal breathing pattern throughout the sleep period. MethodsThe remedē System Therapy (rēST) Study is a prospective non-randomized multicenter international study evaluating long-term safety and effectiveness of the remedē System in the post-market setting. Up to 500 adult patients with moderate to severe CSA will be enrolled and followed up to 5 years at approximately 50 sites in the United States and Europe. Safety objectives include evaluation of adverse events related to the implant procedure, device or delivered therapy, death, and hospitalizations. Effectiveness endpoints include assessment of changes in sleep-disordered breathing metrics from polysomnograms and home sleep tests, changes in daytime sleepiness using the Epworth Sleepiness Scale, and changes in QoL using the PROMIS-29 and Patient Global Assessment questionnaires. The subgroup of patients with heart failure will undergo additional assessments including echocardiography to assess cardiac reverse remodeling, 6-min walk distance, QoL assessment by Kansas City Cardiomyopathy Questionnaire and measurement of biomarkers. ConclusionThis will be the largest prospective study evaluating long-term safety and effectiveness of transvenous phrenic nerve stimulation for the treatment of moderate to severe CSA in adult patients.

Efficacy of Doppler echocardiography-guided ivabradine therapy.

The purpose of this study was to evaluate the advantage of heart rate (HR) modulation using ivabradine referring Doppler echocardiography over the conventional ivabradine therapy without echocardiography guide in patients with systolic heart failure. From October 2020, our institute updated the protocol of ivabradine therapy, in which HR was optimized to minimize the overlap between the two left ventricular inflow waves using Doppler echocardiography (echo-guided group). The degree of cardiac reverse remodeling at 3-month follow-up was compared between the echo-guided group and the conventional ivabradine therapy group treated before October 2020. A total of 28 patients (62years old, 17 men) were included, and 18 patients were from echo-guided group. Left ventricular ejection fraction increased significantly in the echo-guided group (from 41% [28%, 49%] to 55% [37%, 66%], p = 0.007), whereas it remained unchanged in the conventional group (p = 0.333). Systolic blood pressure and the daily dose of carvedilol increased significantly only in the echo-guided group (p = 0.009 and p = 0.001, respectively). Among those with systolic heart failure, a Doppler echocardiography guide might be a promising therapeutic tool in modulating HR by ivabradine in facilitating reverse remodeling.

Treatment of cardiac resynchronization therapy non-responders: current approaches and new frontiers

ABSTRACT Introduction Cardiac resynchronization therapy (CRT) has developed into a very effective technology for patients with decreased systolic function and has substantially improved patients’ clinical course. However, non-responsiveness to CRT, described as lack of reverse cardiac chamber remodeling, leading to lack to improve symptoms, heart failure hospitalizations or mortality, is common, rather unpredictable, and not fully understood. Areas covered This article aims to discuss key factors that are impacting CRT response, from patient selection to LV lead position, to structured follow-up in CRT clinics. Secondly, common causes and interventions for CRT non-responsiveness are discussed. Next, insight is given into technologies representing new and feasible interventions as well as pacing strategies in this group of patients that remain challenging to treat. Finally, an outlook is given into future scientific development. Expert opinion Despite the progress that has been made, CRT non-response remains a significant and complex problem. Patient management in interdisciplinary teams including heart failure, imaging, and cardiac arrhythmia experts appears critical as complexity is increasing and CRT non-response often is a multifactorial problem. This will allow optimization of medical therapy, and the use of new integrated sensor technologies and telemedicine to ultimately optimize outcomes for all patients in need of CRT.

The Role of Interferons in Cardiac Remodeling after Acute Myocardial Infarction.

To determine the relationship of serial interferon (IFN) measurements and adverse cardiac remodeling (AR) after myocardial infarction (MI). Observational multi-centre study. Departments of Cardiology of Diskapi Yildirim Beyazit Training and Research Hospital, Ataturk Training and Research Hospital, Numune Training and Research Hospital, and Dr. Nafiz Sincan Korez State Hospital, Turkey, from June 2015 to June 2020. Forty-seven patients with acute MI were included. IFN levels were measured on the first day and at 14 days and 45 days post-MI. Reverse cardiac remodeling (RR) and AR were defined as the reduction of left ventricular end-diastolic volume by ≥12% and increases of ≥12% by cardiac magnetic resonance imaging at the 6-month follow-up. Statistical significance was accepted as p<0.05. Median IFN-α (50.1 vs. 34.8 pg/mL, p=0.035), IFN-β (39.1 vs. 23.0 pg/mL, p=0.013), and IFN-γ (26.7 vs. 18.5 pg/mL, p=0.023) levels on the first day post-MI were higher in the AR group compared to the RR group. At 14 days post-MI, IFN levels had decreased in the AR group, while they had not changed in the RR group. At 45 days post-MI, IFN levels were similar between the AR and RR groups. High IFN-α level on the first-day post-MI was an independent predictor of AR (OR: 1.23, 95% CI: 1.06-1.43, p=0.008). High IFN levels in the acute phase post-MI are associated with AR. Among IFNs, IFN-α is an important predictor of AR. Stable IFN levels appear to be associated with cardiac healing. Cardiac remodeling, Interferons, Inflammation, Myocardial infarction.

Association of sex hormone dynamics with 10-year survival in men with implanted cardiac resynchronization therapy devices

Aim. To assess association of different dynamics of sex hormones with 10-year survival in men with congestive heart failure (CHF) and implanted cardiac resynchronization therapy (CRT) devices.Methods. Based on tercile of testosterone at the end of the study (TESend), 157 men with CRT (mean age 58.7±9.7 years old; 95 men (60.5%) w/ ischemic CHF) were divided into 3 groups: gr. I (n=52) - TESend&lt;13.3 nmol/l; gr. II (n=53) - TESend&gt;13.3&lt;19.2 nmol/l; gr. III (n=52) - TESend&gt;19.2 nmol/l. Parameters of echocardiography (Echo) were investigated in dynamics, N-terminal fragment of probrain natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), total and free testosterone (TES), estradiol (E2), sex hormone-binding globulin (SHBG), progesterone (PGN), dehydroepiandrosterone sulfate (DHEAS), E2/TES ratio were tested in plasma. Survival in groups was assessed using Kaplan-Meier method.Results. Groups were comparable in age, presence of ischemic CHF, arterial hypertension and surgeries on myocardial revascularization. Higher incidence of atrial fibrillation, obesity, complete left bundle branch block, tendency to higher incidence of diabetes mellitus and higher body mass index was revealed in gr. I compared to gr. III. At baseline, groups didn’t differ in Echo parameters; the highest TES levels were found in gr. III. After CRT, there was less reverse cardiac remodeling, decrease of TES level (p&lt;0.001) in gr. I vs increase of TES level in gr. II (p=0.041) and gr. III (&lt;0.001); E2 level increased (p=0.008), levels of NT-proBNP and IL-6 decreased only in gr. III. In absence of dynamics of E2/TES index and DHEAS level in groups, E2/TES index was the highest and DHEAS level was the lowest in gr. I after CRT. 10-year survival of groups was 17.6%, 42.8%, 46.2% (Log Rank test I-II=0.016; Log Rank test I-III=0.004; Log Rank test II-III=0.528).Conclusion. Obtained results indicated different dynamics of sex steroids after CRT. Sex hormones variation pattern, interrelated with increase in levels of testosterone, estradiol, dehydroepiandrosterone sulfate and decrease in testosterone to estradiol ratio, was associated with better 10-year survival in men with implantable CRT devices with greater reverse cardiac remodeling and reduction in activity of systemic immune inflammation.

Pharmacological Anti-Remodelling Effects of Disease-Modifying Drugs in Heart Failure with Reduced Ejection Fraction.

Cardiac remodelling is an adverse phenomenon linked to heart failure progression and an important contributor to heart failure severity. Cardiac remodelling could represent the real therapeutic goal in the treatment of patients with heart failure with reduced ejection fraction, being potentially reversed through different pharmacotherapies. Currently, there are well-established drugs such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and β-blockers with anti-remodelling effects; recently, angiotensin receptor neprilysin inhibitor effects on inhibiting cardiac remodelling (improving N-terminal pro-B-type natriuretic peptide levels, echocardiographic parameters of reverse cardiac remodelling and right ventricular function in patients with heart failure with reduced ejection fraction) were demonstrated. More recently, hemodynamic consequences of gliflozins, reduced cardiac hydrostatic pressure as a possible cause of ventricular remodelling and hypertrophy were proposed to explain potential anti-remodelling effects of gliflozins. Gliflozins exert their cardioprotective effects by attenuating myofibroblast activity and collagen-mediated remodelling. Another postulated mechanism is represented by the reduction in sympathetic activity, through the reduction in renal afferent nervous activity and the suppression of central reflex mechanisms. Benefits of gliflozins on left ventricular hypertrophy, dilation, and systolic and diastolic function were also described. In this review, we aimed to provide a wide overview on cardiac remodelling with a particular focus on possible anti-remodelling effects of angiotensin receptor neprilysin inhibitors and gliflozins.

Fibro-inflammatory recovery and type 2 diabetes remission following a low calorie diet but not exercise training: A secondary analysis of the DIASTOLIC randomised controlled trial.

AimsTo investigate the relationship between fibro‐inflammatory biomarkers and cardiovascular structure/function in people with Type 2 Diabetes (T2D) compared to healthy controls and the effect of two lifestyle interventions in T2D.MethodsData were derived from the DIASTOLIC randomised controlled trial (RCT) and includes a comparison between those with T2D and the matched healthy volunteers recruited at baseline. Adults with T2D without cardiovascular disease (CVD) were randomized to a 12‐week intervention either: (1) exercise training, (2) a low‐energy (∼810 kcal/day) meal‐replacement plan (MRP) or (3) standard care. Principal Component and Fisher's linear discriminant analysis were used to investigate the relationships between MRI acquired cardiovascular outcomes and fibro‐inflammatory biomarkers in cases versus controls and pre‐ and post‐intervention in T2D.ResultsAt baseline, 83 people with T2D (mean age 50.5 ± 6.4; 58% male) and 36 healthy controls (mean age 48.6 ± 6.2; 53% male) were compared and 76 people with T2D completed the RCT for pre‐ post‐analysis. Compared to healthy controls, subjects with T2D had adverse cardiovascular remodelling and a fibro‐inflammatory profile (20 differentially expressed biomarkers). The 3D data visualisations showed almost complete separation between healthy controls and those with T2D, and a marked shift towards healthy controls following the MRP (15 biomarkers significantly changed) but not exercise training.ConclusionsFibro‐inflammatory pathways and cardiovascular structure/function are adversely altered before the onset of symptomatic CVD in middle‐aged adults with T2D. The MRP improved the fibro‐inflammatory profile of people with T2D towards a more healthy status. Long‐term studies are required to assess whether these changes lead to continued reverse cardiac remodelling and prevent CVD.

Predictors of sacubitril/valsartan high dose tolerability in a real world population with HFrEF.

The angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (Sac/Val) demonstrated to be superior to enalapril in reducing hospitalizations, cardiovascular and all-cause mortality in patients with ambulatory heart failure and reduced ejection fraction (HFrEF), in particular when it is maximally up-titrated. Unfortunately, the target dose is achieved in less than 50% of HFrEF patients, thus undermining the beneficial effects on the outcomes. In this study, we aimed to evaluate the role of Sac/Val and its titration dose on reverse cardiac remodelling and determine which echocardiographic index best predicts the up-titration success. From January 2020 to June 2021, we retrospectively identified 95 patients (65.6 [59.1-72.8] years; 15.8% females) with chronic HFrEF who were prescribed Sac/Val from the HF Clinics of 5 Italian University Hospitals and evaluated the tolerability of Sac/Val high dose (the ability of the patient to achieve and stably tolerate the maximum dose) as the primary endpoint in the cohort. We used a multivariable logistic regression analysis, with a stepwise backward selection method, to determine the independent predictors of Sac/Val maximum dose tolerability, using, as candidate predictors, only variables with a P-value < 0.1 in the univariate analyses. Candidate predictors identified for the multivariable backward logistic regression analysis were age, sex, body mass index (BMI), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), dyslipidaemia, atrial fibrillation, systolic blood pressure (SBP), baseline tolerability of ACEi/ARBs maximum dose, left ventricle global longitudinal strain (LVgLS), LV ejection fraction (EF), tricuspid annulus plane systolic excursion (TAPSE), right ventricle (RV) fractional area change (FAC), RV global and free wall longitudinal strain (RVgLS and RV-FW-LS). After the multivariable analysis, only one categorical (ACEi/ARBs maximum dose at baseline) and three continuous (younger age, higher SBP, and higher TAPSE), resulted significantly associated with the study outcome variable with a strong discriminatory capacity (area under the curve 0.874, 95% confidence interval (CI) (0.794-0.954) to predict maximum Sac/Val dose tolerability. Our study is the first to analyse the potential role of echocardiography and, in particular, of RV dysfunction, measured by TAPSE, in predicting Sac/Val maximum dose tolerability. Therefore, patients with RV dysfunction (baseline TAPSE <16mm, in our cohort) might benefit from a different strategy to titrate Sac/Val, such as starting from the lowest dose and/or waiting for a more extended period of observation before attempting with the higher doses.

Role of Echocardiography in the Management of Patients with Advanced (Stage D) Heart Failure Related to Nonischemic Cardiomyopathy.

Echocardiography (ECHO) is indispensable for evaluation of patients with terminal chronic heart failure (HF) who require transplantation or mechanical circulatory support by a left- or biventricular assist device (LVAD or BiVAD, respectively). In LVAD candidates, ECHO represents the first-line investigation necessary for a timely discovery of heart-related risk factors for potentially life-threatening post-operative adverse events, including identification of patients who necessitate a biventricular support. ECHO is also required for intra-operative guiding of VAD implantation and finding of the most appropriate setting of the device for an optimal ventricular unloading, postoperative surveillance of the VAD support, and monitoring of the RV changes in LVAD recipients. Thanks to the ECHO, which has decisively contributed to the proof that prolonged VAD support can facilitate cardiac reverse remodeling and functional improvement to levels which allow successful weaning of carefully selected patients from LVAD or BiVAD, the previous opinion that chronic non-ischemic cardiomyopathy (NICMP) is irreversible could be refuted. In patients with normalized and stable right heart catheter-derived hemodynamic parameters obtained at short-term interruptions of VAD support, ECHO has proved able to predict post-weaning long-term freedom from HF recurrence in patients with pre-implant terminal chronic NICMP. The purpose of this article is to offer an actualized theoretical and practical support for clinicians engaged in this particularly challenging and topical issue especially due to the new practical aspects which have emerged in conjunction with the growing use of long-term ventricular assist devices as bridge-to-transplantation or as destination therapy, as well as the increasing evidence that, in some patients, such VAD can become a bridge-to-recovery, allowing the removal of the device after a longer support time.

Three-year outcomes of transcatheter aortic valve implantation for bicuspid versus tricuspid aortic stenosis.

Transcatheter aortic valve implantation (TAVI) might be a feasible treatment option for more patients with bicuspid aortic valve (BAV) stenosis. However, long-term follow-up data in this population are scarce. The aim of this study was to evaluate three-year outcomes after TAVI in patients with BAV. A total of 246 consecutive patients who underwent TAVI at a single centre in China between March 2013 and February 2018 were enrolled in this study. Clinical outcomes, health status and echocardiography were followed and recorded for three years. Among 109 (44.3%) BAV patients, 61.5% were Type 0 and 36.7% were Type 1 BAV patients. BAV patients were younger (75 vs 77 years, p=0.041) and had a lower Society of Thoracic Surgeons (STS) score (5.09 vs 6.00, p=0.026) compared to tricuspid aortic valve (TAV) patients. There were no differences in three-year survival rates between bicuspid and tricuspid patients (87.1% vs 79.5%, log-rank p=0.126). Multivariate Cox regression analysis adjusting for confounding factors revealed a similar risk of all-cause mortality in the BAV population (hazard ratio [HR] 0.86, 95% confidence interval [CI]: 0.44-1.70, p=0.666). Except for the rate of permanent pacemaker implantation that was lower in BAV patients (11.9% vs 21.9%, p=0.041), the incidence of other clinical adverse events was comparable between the two groups. Both BAV and TAV patients showed an obvious improvement in valve haemodynamics, which was sustained for three years. In addition, similar left ventricular reverse remodelling was found during follow-up. BAV patients showed similar satisfactory three-year clinical outcomes, persistent valve haemodynamics improvement, and obvious cardiac reverse remodelling after TAVI compared to TAV patients.

Impact of New-Onset Persistent Left Bundle Branch Block on Reverse Cardiac Remodeling and Clinical Outcomes After Transcatheter Aortic Valve Replacement.

BackgroundThe clinical implication of new-onset left bundle branch block (LBBB) after transcatheter aortic valve replacement (TAVR) remains controversial. We investigated the impact of new-onset persistent LBBB on reverse cardiac remodeling and clinical outcomes after TAVR.MethodsAmong 478 patients who had undergone TAVR for symptomatic severe aortic stenosis from 2011 to 2021, we analyzed 364 patients after excluding patients with pre-existing intraventricular conduction disturbance or a pacing rhythm before or during the indexed hospitalization for TAVR. Echocardiographic variables of cardiac remodeling at baseline and 1 year after TAVR were comprehensively analyzed. The primary outcome was a composite of cardiovascular death and hospitalization for heart failure. Secondary outcomes were all-cause death and individual components of the primary outcome.ResultNew-onset persistent LBBB occurred in 41 (11.3%) patients after TAVR. The no LBBB group showed a significant increase in the left ventricular (LV) ejection fraction and decreases in LV dimensions, the left atrial volume index, and LV mass index 1 year after TAVR (all p < 0.001). However, the new LBBB group showed no significant changes in these parameters. During a median follow-up of 18.1 months, the new LBBB group experienced a higher incidence of primary outcomes [hazard ratio (HR): 5.03; 95% confidence interval (CI): 2.60–9.73; p < 0.001] and all-cause death (HR: 2.80; 95% CI: 1.38–5.69; p = 0.003). The data were similar after multivariable regression analysis.ConclusionNew-onset persistent LBBB after TAVR is associated with insufficient reverse cardiac remodeling and increased adverse clinical events.

C72 THE EFFECTS OF BATRIATIC SURGERY ON CARDIO–METABOLIC PROFILE AND CARDIAC REMODELING

Abstract Background Obesity is associated with cardiac remodeling resulting in hypertrophy of the left ventricle (LV) with a predominantly concentric pattern. LV remodeling and fibrosis induce mechanical and electrical dysfunction of the myocardial tissue, an increase in cardiac output, an increase of myocardial workload and mean arterial pressure. Objective To evaluate the impact of bariatric surgery, and therefore of anthropometric and cardio–metabolic variations, on cardiac structure and function. Methods Twenty–six obese patients treated with bariatric surgery were enrolled. All the patients at baseline and at 6 and 12 months underwent a complete anthropometrical evaluation, laboratory determinations and echocardiogram evaluation. The IR has been assessed by HOMA–IR. The patients were divided into two groups: the first group (8 patients) carried out a follow–up at 6 months post–surgery; the second group (18 patients) at 12 months post–surgery. Results As expected, an improvement in the anthropometric and metabolic profile in patients treated with bariatric surgery was observed. Echocardiographic data showed a significant increase in the Ejection Fraction (P &amp;lt; 0.001) and the E/A Ratio (P &amp;lt; 0.001) 6 months after bariatric surgery, a significant reduction in the Interventricular Septum thickness at 6 months (P &amp;lt; 0.001) and at 12 months (P &amp;lt; 0.002) post–surgery and a significant reduction in the Left Ventricular Mass at 6 months (P = 0.02) and at 12 months (P = 0.05) after bariatric surgery. A reduction no significant in the Left Ventricular posterior wall thickness has been observed. Conclusions Our data showed an increase of the systolic function, an increase of the left ventricular diastolic compliance and a reduction in subclinical cardiac organ damage. Therefore, significant weight loss obtained with bariatric surgery may lead to reverse cardiac remodeling, associated with beneficial effects on myocardial structure and systo-diastolic function.

Sodium-glucose co-transporter-2 inhibitors in heart failure with reduced ejection fraction: Current evidence and future perspectives.

The sodium-glucose co-transporter-2 (SGLT2) inhibitors were developed as glucose-lowering drugs to treat type 2 diabetes (T2D). However, significant reductions in clinical outcomes have now been demonstrated in patients with heart failure with reduced ejection fraction (HFrEF), irrespective of the presence of T2D. Multiple hypotheses have been proposed for the underlying mechanisms, and the data to support these proposals are emerging. To review the clinical outcome data with SGLT2 inhibitors in HFrEF and the data to support the mechanisms for these clinical effects. Literature review was supported by a PubMed search for relevant articles up to 19 April 2022. Current data support increased diuresis and reverse cardiac remodelling as important mechanisms for the reductions in heart failure hospitalizations and mortality observed with SGLT2 inhibitors (empagliflozin or dapagliflozin) in patients with HFrEF. Alteration in intrarenal haemodynamic is likely contributing to the observed renoprotective effect of SGLT2 inhibitors. Solid clinical data support the current recommendations to use empagliflozin or dapagliflozin in HFrEF. The underlying mechanisms likely include changes in cardiac and intrarenal haemodynamic. Yet, these mechanisms do not seem to solely explain the observed magnitude of clinical effect with SGLT2 inhibitors in HFrEF, and other mechanisms may contribute.

EGR1 Is Implicated in Right Ventricular Cardiac Remodeling Associated with Pulmonary Hypertension.

Simple SummaryPulmonary hypertension (PH) is a condition characterized by increased arterial pressure in the pulmonary vasculature. PH strains the right heart, which compensates for the increased afterload by hypertrophy. This eventually leads to heart failure, which represents the leading cause of death in PH patients. Surgeries normalize pulmonary arterial pressures and cause the regeneration of hypertrophic right hearts. Nonetheless, the events involved in cardiac recovery are largely unknown. We therefore investigated the gene expression profiles of hypertrophic and regenerated right hearts of two different types of PH patients. Intriguingly, the PH subtypes displayed a rather unique gene alteration signature, before as well as after surgery. While genes associated with muscle cell development were upregulated in one group, genes involved in the same molecular process were downregulated in a different PH group following surgery. However, we were able to identify a profibrotic factor, namely early growth response 1, in both PH groups. A role for this molecule in hypertrophic right hearts was further confirmed by immunohistochemistry. In conclusion, our study described the gene expression signatures of failing and recovered right hearts of PH patients. The findings presented here might help to identify attractive therapeutic candidates for PH patients considered inoperable.Background: Pulmonary hypertension (PH) is a vasoconstrictive disease characterized by elevated mean pulmonary arterial pressure (mPAP) at rest. Idiopathic pulmonary arterial hypertension (iPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) represent two distinct subtypes of PH. Persisting PH leads to right ventricular (RV) hypertrophy, heart failure, and death. RV performance predicts survival and surgical interventions re-establishing physiological mPAP reverse cardiac remodeling. Nonetheless, a considerable number of PH patients are deemed inoperable. The underlying mechanism(s) governing cardiac regeneration, however, remain largely elusive. Methods: In a longitudinal approach, we profiled the transcriptional landscapes of hypertrophic RVs and recovered hearts 3 months after surgery of iPAH and CTEPH patients. Results: Genes associated with cellular responses to inflammatory stimuli and metal ions were downregulated, and cardiac muscle tissue development was induced in iPAH after recovery. In CTEPH patients, genes related to muscle cell development were decreased, and genes governing cardiac conduction were upregulated in RVs following regeneration. Intriguingly, early growth response 1 (EGR1), a profibrotic regulator, was identified as a major transcription factor of hypertrophic RVs in iPAH and CTEPH. A histological assessment confirmed our biocomputational results, and suggested a pivotal role for EGR1 in RV vasculopathy. Conclusion: Our findings improved our understanding of the molecular events driving reverse cardiac remodeling following surgery. EGR1 might represent a promising candidate for targeted therapy of PH patients not eligible for surgical treatment.

The benefits of the earlier use of sacubitril/valsartan in de novo heart failure with reduced ejection fraction patients.

AimsWe evaluated the clinical outcomes and trajectory of cardiac reverse remodelling according to the timing of sacubitril/valsartan (Sac/Val) use in patients with heart failure (HF) with reduced ejection fraction (HFrEF).Methods and resultsPatients with de novo HFrEF who used Sac/Val between June 2017 and October 2019 were retrospectively enrolled. Patients were grouped into the earlier use group (initiation of Sac/Val < 3 months after the first HFrEF diagnosis) and the later use group (initiation of Sac/Val ≥ 3 months after the first HFrEF diagnosis). Primary outcome was a composite of HF hospitalization and cardiac death. Secondary outcomes were HF hospitalization, cardiac death, all‐cause death, significant ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation), and echocardiographic evidence of cardiac reverse remodelling including left ventricular ejection fraction (LVEF) change during follow‐up. Among 115 enrolled patients, 67 were classified in the earlier use group, and 48 were classified in the later use group. Mean period of HFrEF diagnosis to Sac/Val use was 52.1 ± 14.3 days in the earlier use group, and 201.8 ± 127.3 days in the later use group. During the median follow‐up of 721 days, primary outcome occurred in 21 patients (18.3%). The earlier use group experienced significantly fewer primary outcome than the later use group (10.4% vs. 29.2%, P = 0.010). The Kaplan–Meier survival curve showed better event‐free survival in the earlier use group than in the later use group (log rank = 0.017). There were no significant differences in cardiac death, all‐cause death, and ventricular arrhythmia between two groups (1.5% vs. 2.1%, P = 0.811; 1.5% vs. 4.2%, P = 0.375; 3.0% vs. 0%, P = 0.227, respectively). Despite a significantly lower baseline LVEF in the earlier use group (21.3 ± 6.4% vs. 24.8 ± 7.9%, P = 0.012), an early prominent increase of LVEF was noted before 6 months (35.2 ± 11.9% vs. 27.8 ± 8.8%, P = 0.007). A delayed improvement of LVEF in the later use group resulted in similar LVEF at last follow‐up in both groups (40.7 ± 13.4% vs. 39.4 ± 10.9%, P = 0.686). Although the trajectory of left ventricular remodelling showed similar pattern in two groups, left atrial (LA) reverse remodelling was less prominent in the later use group during the follow‐up period (final LA volume index: 43.6 ± 14.3 mL/m2 vs. 55.2 ± 17.1 mL/m2, P = 0.011).ConclusionsEarlier use of Sac/Val was related with better clinical outcome and earlier left ventricular reverse remodelling. Remodelling of LA was less prominent in the later use group implying delayed response in diastolic function.

Reverse cardiac remodeling after fluid balance optimization in patients with end-stage renal disease.

BackgroundIn patients with end‐stage renal disease (ESRD) undergoing hemodialysis, cardiovascular diseases, and in particular chronic heart failure are the leading causes of morbidity and mortality. Nevertheless, few data are available about the impact of fluid optimization on echocardiographic parameters of cardiac function in patients with ESRD.Methods and ResultsIn five patients with ESRD undergoing hemodialysis who had developed nonischemic dilated cardiomyopathy, an optimal fluid volume management based on a strict bioelectrical impedance analysis‐assisted dry weight target and dietary sodium and water restriction led to left ventricular reverse remodeling and improvement in hemodynamic parameters. The reverse remodeling further improved after kidney transplantation.ConclusionsThis case series supports the possible beneficial effect of volume status optimization on cardiac function and the potential reversibility of cardiac dysfunction after kidney transplantation.

Cardiometabolic-based chronic disease: adiposity and dysglycemia drivers of heart failure.

Heart failure (HF) is a complex clinical syndrome, associated with high rates of mortality, hospitalization, and impairment of quality of life. Obesity and type 2 diabetes are major cardiometabolic drivers, represented as distinct stages of adiposity- and dysglycemia-based chronic disease (ABCD, DBCD), respectively, and leading to cardiometabolic-based chronic disease (CMBCD). This review focuses on one aspect of the CMBCD model: how ABCD and DBCD influence genesis and progression of HF phenotypes. Specifically, the relationships of ABCD and DBCD stages with structural and functional heart disease, HF risk, and outcomes in overt HF are detailed. Also, evidence-based lifestyle, pharmacological, and procedural interventions that promote or reverse cardiac remodeling and outcomes in individuals at risk or with HF are discussed. In summary, driver-based chronic disease models for individuals at risk or with HF can expose prevention targets for more comprehensive interventions to improve clinical outcomes. Future randomized trials that investigate structured lifestyle, pharmacological, and procedural therapies specifically tailored for the CMBCD model are needed to develop personalized care plans to decrease HF susceptibility and improve outcomes.

Implication of Mineralocorticoid Receptor Antagonist Esaxerenone in Patients with HFpEF

<h3>Purpose</h3> The implications of mineralocorticoid receptor antagonists, including the newly-introduced esaxerenone, on cardiac reverse remodeling in patients with HFpEF remain uncertain. <h3>Methods</h3> We retrospectively included patients with HFpEF who received esaxerenone for resistant hypertension between Nov 2019 and Jul 2021. Changes in left ventricular mass index (LVMI) were compared between the six-month pre-treatment period (without esaxerenone) and the six-month treatment period (on esaxerenone). <h3>Results</h3> Thirty-three patients (median age 74 [70, 81] years, 33% men, systolic blood pressure 135 [123, 148] mmHg) were included and completed 6-month esaxerenone therapy without any adverse events. During the pre-treatment period, systolic blood pressure decreased significantly (p = 0.009) whereas LVMI remained unchanged (p = 0.30; Figure 1). During the treatment period with esaxerenone, both systolic blood pressure and LVMI decreased significantly (p = 0.003 and p = 0.001, respectively). <h3>Conclusion</h3> Esaxerenone may have beneficial effects of reverse remodeling in patients with HFpEF when used to treat hypertension. Further studies are needed to understand which patient populations may see greater benefits.

Multicenter-Derived Clinical Score Predicts Structural and Functional Cardiac Improvement in Chronic Heart Failure Patients Undergoing Mechanical Circulatory Support

<h3>Purpose</h3> Although significant reverse cardiac remodeling is required for an LVAD-supported patient to be considered for device weaning, multiple factors including patient willingness, physician expertise, and center experience influence this complex decision. Existing predictive models defining cardiac recovery as device removal might underestimate reverse remodeling rates and lack accuracy in identifying patients prone to improve cardiac structure and function. We sought to develop a predictive tool to identify patients with such potential, independent of the decision to deactivate a durable, surgically deployed device. <h3>Methods</h3> Chronic HF patients (N=703) requiring continuous-flow LVADs were evaluated. After excluding patients with acute HF and/or <3 months post-LVAD follow up, 3 US programs contributed 390 patients (derivation cohort), while 5 US programs formed the validation cohort (n=245). We defined responders as patients with an LVEF ≥40% and LVEDD ≤6.0 cm within a year on LVAD support. Multivariable logistic regression on the derivation set yielded a predictive model, which was externally tested; a predictive score was developed. <h3>Results</h3> Overall, 18.5% of the patients were responders. Compared to the validation, patients in the derivation cohort were more likely white (83 vs 69%; p<0.001), with ischemic HF (42 vs 33%; p=0.04), and longer HF duration (88 vs 66 months; p<0.001). Multivariable predictors of responders and the derived scoring system are shown in the <b>Figure</b> (c-statistic 0.74 [95% CI: 0.66-0.83] and 0.71 [95% CI: 0.59-0.77] in the derivation and validation set). <h3>Conclusion</h3> We propose a novel score to predict significant cardiac improvement on LVAD support achieving good discriminative performance in distinct, heterogeneous, contemporary cohorts. This tool can be useful in selecting patients to implement diagnostic and therapeutic protocols to promote reverse remodeling and myocardial recovery.

First signs of reverse cardiac remodeling following one-month, low dose add-on sacubitril-valsartan therapy in patients with advanced systolic heart failure

We investigated the early effects of low dose sacubitril/valsartan (S/V) on cardiac reverse remodeling (CRR). Methods: In 37 patients (45- excluded 8pts,mean age 64.5±17.5 years, five females), 24/26 mg S/V BID was started, and the second evaluation was performed after month. Results: Following CRR parameters improved: LVEDD (-∆2,9±2.6 mm; Student’s t-test: p =0.0098), LVESD (-∆2,4±2.5 mm; Student’s t-test: p=0.0092), LVEDV (-∆14.6±33.1 mL; Wilcoxon test: p = 0.0412), LVESV (-∆13.4±30.6 mL; Wilcoxon test: p =0.0442), LAVI (-∆8.7±37.7 mL/m2; Wilcoxon test: p = 0.0012), and EROA (-∆0.09±0.01 cm2; Student’s t-test: p = 0.0318). In opposite to LVEF, global longitudinal strain (GLS) changed from -6.6% to -7.9% (absolute improvement of 16%, Wilcoxon test: p=0.0013). Other parameters improving: 6-MWT (+∆65.4±75.8 m; Wilcoxon test: p = 0.0013) and the quality of life (MLHFQ 22 vs 16 scores; Student’s t-test: p= 0.0098), NT-pro BNP (-∆1203.1±3121.4 pg/mL; Student’s t-test: p = 0.0348) and troponin T (-∆ 4.7±9.4 pg/mL, Wilcoxon test: p = 0.0041). Correlation between GLS and LVESV (Pearson's correlation coefficient: r = -0,4596, p = 0.0239) was found. ROC curve analysis showed that in the group with severe systolic dysfunction (GLS&lt; -8%) clinical improvement (6MWT: AUC = 0.692, p = 0.0383) and CRR (MRvol: AUC = 0.736, p = 0.0062; LAVI: AUC = 0.710, p = 0.0414) are more likely to occur. Conclusions: Low-dose (24/26 mg BID) S/V therapy initiates CRR. S/V should be started in patients with less impaired LV systolic function (GLS &lt; -8%) because CRR and clinical improvement are more likely to develop.