Proteomic Profiling of Dilated Cardiomyopathy Plasma Samples ─ Searching for Biomarkers with Potential to Predict the Outcome of Therapy.

Determination of the prognosis and treatment outcomes of dilated cardiomyopathy is a serious problem due to the lack of valid specific protein markers. Using in-depth proteome discovery analysis, we compared 49 plasma samples from patients suffering from dilated cardiomyopathy with plasma samples from their healthy counterparts. In total, we identified 97 proteins exhibiting statistically significant dysregulation in diseased plasma samples. The functional enrichment analysis of differentially expressed proteins uncovered dysregulation in biological processes like inflammatory response, wound healing, complement cascade, blood coagulation, and lipid metabolism in dilated cardiomyopathy patients. The same proteome approach was employed in order to find protein markers whose expression differs between the patients well-responding to therapy and nonresponders. In this case, 45 plasma proteins revealed statistically significant different expression between these two groups. Of them, fructose-1,6-bisphosphate aldolase seems to be a promising biomarker candidate because it accumulates in plasma samples obtained from patients with insufficient treatment response and with worse or fatal outcome. Data are available via ProteomeXchange with the identifier PXD046288.

Cardiac reverse remodeling in a mouse model with many phenotypical features of heart failure with preserved ejection fraction: effects of modifying lifestyle.

Multiple factors cause heart failure with preserved ejection fraction (HFpEF) and involve various systems. HFpEF prevalence is rapidly rising, and its prognosis remains poor after the first hospitalization. Adopting a more active lifestyle has been shown to provide beneficial clinical outcomes for patients with HFpEF. Using a two-hit HfpEF murine model, we studied cardiac reverse remodeling (RR) after stopping the causing stress and introducing voluntary exercise (VE). We checked in 2-mo-old male and female C57Bl6/J mice the heart's response to angiotensin II (ANG II; 1.5 mg/kg/day for 28 days) fed or not with a high-fat diet (HFD). Then, ANG II and/or the HFD were stopped, and VE was started for an additional 4 wk. ANG II and ANG II + HFD (metabolic-hypertensive stress, MHS) caused cardiac hypertrophy (CH) and myocardial fibrosis, left ventricular (LV) concentric remodeling, atrial enlargement, and reduced exercise capacity. HFD alone induced CH and LV concentric remodeling in female mice only. CH and LV concentric remodeling were reversed 4 wk after stopping ANG II, starting VE, and a low-fat diet. Left atrial enlargement and exercise capacity were improved but differed from controls. We performed bulk LV RNA sequencing and observed that MHS upregulated 58% of the differentially expressed genes (DEGs) compared with controls. In the RR group, compared with MHS animals, 60% of the DEGs were downregulated. In an HfpEF mouse model, we show that correcting hypertension, diet, and introducing exercise can lead to extensive cardiac reverse remodeling.NEW & NOTEWORTHY Using a two-hit murine model of heart failure with preserved ejection fraction (HfpEF), combining elevated blood pressure, obesity, and exercise intolerance in male and female animals, we showed that correction of hypertension, normalization of the diet, and introduction of voluntary exercise could help reverse the remodeling of the left ventricle and double exercise capacity. We also identify genes that escape normalization after myocardial recovery and differences between males' and females' responses to stress and recovery.

4D Flow Cardiac MR in Primary Mitral Regurgitation.

BACKGROUND: Four-dimensional-flow cardiac MR (4DF-MR) offers advantages in primary mitral regurgitation. The relationship between 4DF-MR-derived mitral regurgitant volume (MR-Rvol) and the post-operative left ventricular (LV) reverse remodeling has not yet been established. PURPOSE: To ascertain if the 4DF-MR-derived MR-Rvol correlates with the LV reverse remodeling in primary mitral regurgitation. STUDY TYPE: Prospective, single-center, two arm, interventional vs. nonintervention observational study. POPULATION: Forty-four patients (male N = 30; median age 68 [59-75]) with at least moderate primary mitral regurgitation; either awaiting mitral valve surgery (repair [MVr], replacement [MVR]) or undergoing "watchful waiting" (WW). FIELD STRENGTH/SEQUENCE: 5 T/Balanced steady-state free precession (bSSFP) sequence/Phase contrast imaging/Multishot echo-planar imaging pulse sequence (five shots). ASSESSMENT: Patients underwent transthoracic echocardiography (TTE), phase-contrast MR (PMRI), 4DF-MR and 6-minute walk test (6MWT) at baseline, and a follow-up PMRI and 6MWT at 6 months. MR-Rvol was quantified by PMRI, 4DF-MR, and TTE by one observer. The pre-operative MR-Rvol was correlated with the post-operative decrease in the LV end-diastolic volume index (LVEDVi). STATISTICAL TESTS: Included Student t-test/Mann-Whitney test/Fisher's exact test, Bland-Altman plots, linear regression analysis and receiver operating characteristic curves. Statistical significance was defined as P < 0.05. RESULTS: While Bland-Altman plots demonstrated similar bias between all the modalities, the limits of agreement were narrower between 4DF-MR and PMRI (bias 15; limits of agreement -36 mL to 65 mL), than between 4DF-MR and TTE (bias -8; limits of agreement -106 mL to 90 mL) and PMRI and TTE (bias -23; limits of agreement -105 mL to 59 mL). Linear regression analysis demonstrated a significant association between the MR-Rvol and the post-operative decrease in the LVEDVi, when the MR-Rvol was quantified by PMRI and 4DF-MR, but not by TTE (P = 0.73). 4DF-MR demonstrated the best diagnostic performance for reduction in the post-operative LVEDVi with the largest area under the curve (4DF-MR 0.83; vs. PMRI 0.78; and TTE 0.51; P = 0.89). DATA CONCLUSION: This study demonstrates the potential clinical utility of 4DF-MR in the assessment of primary mitral regurgitation. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 5.

Prognostic value of mid-term cardiovascular magnetic resonance follow-up in patients with non-ischemic dilated cardiomyopathy: a prospective cohort study.

BACKGROUND: The prognostic value of follow-up cardiovascular magnetic resonance (CMR) in dilated cardiomyopathy (DCM) patients is unclear. We aimed to investigate the prognostic value of cardiac function, structure, and tissue characteristics at mid-term CMR follow-up. METHODS: The study population was a prospectively enrolled cohort of DCM patients who underwent guideline-directed medical therapy with baseline and follow-up CMR, which included measurement of biventricular volume and ejection fraction, late gadolinium enhancement, native T1, native T2, and extracellular volume. During follow-up, major adverse cardiac events (MACE) were defined as a composite endpoint of cardiovascular death, heart transplantation, and heart-failure readmission. RESULTS: Among 235 DCM patients (median CMR interval: 15.3 months; interquartile range: 12.5-19.2 months), 54 (23.0%) experienced MACE during follow-up (median: 31.2 months; interquartile range: 20.8-50.0 months). In multivariable Cox regression, follow-up CMR models showed significantly superior predictive value than baseline CMR models. Stepwise multivariate Cox regression showed that follow-up left ventricular ejection fraction (LVEF; hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.91-0.96; p < 0.001) and native T1 (HR, 1.01; 95% CI, 1.00-1.01; p = 0.030) were independent predictors of MACE. Follow-up LVEF ≥ 40% or stable LVEF < 40% with T1 ≤ 1273 ms indicated low risk (annual event rate < 4%), while stable LVEF < 40% and T1 > 1273 ms or LVEF < 40% with deterioration indicated high risk (annual event rate > 15%). CONCLUSIONS: Follow-up CMR provided better risk stratification than baseline CMR. Improvements in the LVEF and T1 mapping are associated with a lower risk of MACE.

Transcatheter Closure of Atrial Septal Defects with Absent Aortic Rim and the Predictors of Right Atrial Reverse Remodeling: 5 Years Experience in China.

INTRODUCTION: Atrial septal defect (ASD) is one of the most common congenital heart malformations. Although not recommended, a significant proportion of patients with aortic root defects receive ASD closure, some of whom have improved right ventricular function. The study aimed to investigate the safety of interventional therapy in ASD patients with complete aortic rim deficiency and explore the predictors of right atrial (RA) non-reverse remodeling. METHODS: 1,011 patients with ASD who underwent transcatheter closure in the Department of Cardiology, Zhongshan Hospital, affiliated to Fudan University from June 2017 to June 2023 were enrolled in the study. They were divided into a complete aortic rim deficiency group and without absent aortic rim group. Furthermore, patients who had an enlarged RA in the absent aortic rim group were divided into two subgroups according to whether their RA remodeling was reversed post-procedure. Multivariate logistic regression was used to determine the predictors of RA reverse remodeling. RESULTS: During the 1-year follow-up, no major operative complications occurred in all patients with the absence of an aortic rim and a normal edge. After the operation, the right heart remodeling was significantly reversed, multivariate logistic regression analysis was performed, and it was found that no coronary heart disease before an operation, lower plasma creatinine level, and larger RA and RV dimensions were the predictive factors for the reverse of RA remodeling after treatment. CONCLUSION: Transcatheter closure of ASD with complete aortic rim deficiency is safe and feasible. For patients without coronary heart disease, the lower the creatinine value and the lower the tricuspid regurgitation before an operation, the more improvement of RA remodeling after the operation.

Left ventricular reverse remodeling following initiation of sacubitril/valsartan for heart failure with reduced ejection fraction and low blood pressure.

Sacubitril/valsartan has become an important first-line drug for symptomatic heart failure (HF) patients, especially with left ventricular (LV) ejection fraction (LVEF) < 50%. However, the impact of sacubitril/valsartan on cardiovascular outcomes, especially LV reverse remodeling for such patients with low blood pressure, remains uncertain. We retrospectively studied 164 HF patients with LVEF < 50% who were treated with sacubitril/valsartan from two institutions. Echocardiography was performed before and 9.5 ± 5.1 months after initiation of maximum tolerated dose of sacubitril/valsartan. The maximum tolerated dose of sacubitril/valsartan was lower for the low blood pressure group (≤ 100 mmHg in systole) than for the non-low blood pressure group (> 100 mmHg in systole) (165 ± 106 mg vs. 238 ± 124 mg, P = 0.017). As expected, significant LV reverse remodeling was observed in the non-low blood pressure group after initiation of sacubitril/valsartan. It was noteworthy that significant LV reverse remodeling was also observed in the low blood pressure group after initiation of sacubitril/valsartan (LV end-diastolic volume: 177.3 ± 66.0 mL vs. 137.7 ± 56.1 mL, P < 0.001, LV end-systolic volume: 131.6 ± 60.3 mL vs. 94.6 ± 55.7 mL, P < 0.001, LVEF: 26.8 ± 10.3% vs. 33.8 ± 13.6%, P = 0.015). Relative changes in LV volumes and LVEF after initiation of sacubitril/valsartan were similar for the two groups. In conclusion, significant LV reverse remodeling occurred after initiation of sacubitril/valsartan, even in HF patients with LVEF < 50% and systolic blood pressure ≤ 100 mmHg.

Left atrial conduit strain derived from cardiac magnetic resonance is an independent predictor of left ventricular reverse remodeling in patients with nonischemic cardiomyopathy.

BACKGROUND: In some patients with nonischemic cardiomyopathy (NICM), left ventricular (LV) function improves with medical assistance, resulting in left ventricular reverse remodeling (LVRR). However, predictors of LVRR are not fully understood. The left atrium (LA) has been reported as a prognostic predictor in patients with heart failure (HF). The present study aimed to evaluate clinical predictors of LVRR related to LA function on cardiac magnetic resonance (CMR). METHODS: A total of 103 patients with reduced left ventricular ejection fraction (LVEF) were enrolled in this retrospective study between September 2015 and July 2021. CMR parameters, including strain data, were measured in all patients. Echocardiographic data obtained approximately 2 years after enrollment were analyzed to assess LVRR. RESULTS: LVRR occurred in 46 patients (44.7%) during follow-up. The value of LA conduit strain was higher in the LVRR group than in the non-LVRR group (6.6 [interquartile range (IQR): 5.6-9.3]% versus 5.0 [IQR: 3.0-6.2]%; p < 0.001). The multivariate logistic regression analysis showed that LA conduit strain was an independent predictor of LVRR (odds ratio [OR]: 1.216, 95% confidence interval [CI]: 1.050-1.408; p = 0.009). The area under the receiver operating characteristic (ROC) curve of the LA conduit strain was 0.746, and the cutoff value was 6.2%. The Kaplan‒Meier analysis revealed that the incidence of adverse cardiac events was significantly lower in patients with LA conduit strain > 6.2% compared to those with ⩽6.2%. (log-rank test, p = 0.019). CONCLUSIONS: LA conduit strain derived from CMR is an independent predictor of LVRR in patients with NICM.

Early reverse remodeling by echocardiography after transcatheter aortic valve implantation.

INTRODUCTION: Oslo University Hospital is a tertiary center conducting a significant number of transcatheter aortic valve implantation (TAVI) procedures per year. In this follow-up MediPace study, we aimed to investigate early echocardiographic changes in systolic and diastolic functions after TAVI in these patients. METHODS: All patients enrolled in the previous study were contacted 3 months after TAVI for echocardiographic evaluation. Detailed echocardiography was performed 3.5 ± 1.6 months after TAVI, and compared with baseline evaluations. RESULTS: A total of 101 patients were analyzed. Mean age was 80.1 ± 6.8 years and 40% of the patients were female. We observed a significant improvement in global longitudinal strain (GLS) (pre-TAVI -16.8 ± 4.1%, post-TAVI -17.8 ± 3.6%, p < .001), with no notable change in LVEF. More than half of the patients (52%) experienced a significant reverse remodeling with ≥10% decrease in left ventricular mass index (LVMi) following TAVI (pre-TAVI 123.6 ± 32.1 vs. 109.7 ± 28.9 g/m2 post-TAVI, p < .001). Pre-TAVI LVMi was a positive predictor, whereas history of HT was a negative predictor of LVMi reduction. There was no significant improvement in diastolic function following TAVI. Highest degree of paravalvular leakage was mild to moderate and was observed in only 2%. CONCLUSIONS: A significant improvement in GLS and LVMi was found following TAVI. History of hypertension and baseline LVMi were predictors of LVMi change. There was no notable change in diastolic function, including left atrial strain.

Outcomes of Concomitant Maze Procedure in Tricuspid Repair for Severe Tricuspid Regurgitation.

BACKGROUND: We aimed to analyze the impact of concomitant Maze procedure on the clinical and rhythm outcomes, and echocardiographic parameters in tricuspid repair for patients with severe tricuspid regurgitation (TR) and persistent atrial fibrillation (AF). METHODS: Patients who had severe TR and persistent AF and underwent tricuspid valve (TV) repair were included in the study. Both primary TR and secondary TR were included in the current study. The study population was stratified according to Maze procedure. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE) at 15 years post-surgery. Propensity-score matching analyses was performed to adjust baseline differences. RESULTS: Three hundred seventy-one patients who underwent tricuspid repair for severe TR and persistent AF from 1994 to 2021 were included, and 198 patients (53.4%) underwent concomitant Maze procedure. The maze group showed 10-year sinus rhythm (SR) restoration rate of 55%. In the matched cohort, the maze group showed a lower cumulative incidence of cardiac death (4.6% vs. 14.4%, P = 0.131), readmission for heart failure (8.1% vs. 22.2%, P = 0.073), and MACCE (21.1% vs. 42.1%, P = 0.029) at 15 years compared to the non-maze group. Left atrial (LA) diameter significantly decreased in the maze group at 5 years (53.3 vs. 59.6 mm, P < 0.001) after surgery compared to preoperative level, and there was a significant difference in the change of LA diameter over time between the two groups (P = 0.013). CONCLUSION: The Maze procedure during TV repair in patients with severe TR and persistent AF showed acceptable SR rates and lower MACCE rates compared to those without the procedure, while also promoting LA reverse remodeling.

Cardiovascular risk factors during pregnancy impact the postpartum cardiac and vascular reverse remodeling.

Pregnant women with cardiovascular risk (CVR) factors are highly prone to develop cardiovascular disease later in life. Thus, recent guidelines suggest extending the follow-up period to 1 yr after delivery. We aimed to evaluate cardiovascular remodeling during pregnancy and determine which CVR factors and potential biomarkers predict postpartum cardiac and vascular reverse remodeling (RR). Our study included a prospective cohort of 76 healthy and 54 obese and/or hypertensive and/or with gestational diabetes pregnant women who underwent transthoracic echocardiography, pulse-wave velocity (PWV), and blood collection at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy as well as at the 1st/6th/12th mo after delivery. Generalized linear mixed-effects models was used to evaluate the extent of RR and its potential predictors. Pregnant women develop cardiac hypertrophy, as confirmed by a significant increase in left ventricular mass (LVM). Moreover, ventricular filling pressure (E/e') and atrial volume increased significantly during gestation. Significant regression of left ventricular (LV) volume, LVM, and filling pressures was observed as soon as 1 mo postpartum. The LV global longitudinal strain worsened slightly and recovered at 6 mo postpartum. PWV decreased significantly from 1T to 3T and normalized at 1 mo postpartum. We found that arterial hypertension, smoking habits, and obesity were independent predictors of increased LVM during pregnancy and postpartum. High C-reactive protein (CRP) and low ST2/IL33-receptor levels are potential circulatory biomarkers of worse LVM regression. Arterial hypertension, age, and gestational diabetes positively correlated with PWV. Altogether, our findings pinpoint arterial hypertension as a critical risk factor for worse RR and CRP, and ST2/IL33 receptors as potential biomarkers of postpartum hypertrophy reversal.NEW & NOTEWORTHY This study describes the impact of cardiovascular risk factors (CVR) in pregnancy-induced remodeling and postpartum reverse remodeling (up to 1 yr) by applying advanced statistic methods (multivariate generalized linear mixed-effects models) to a prospective cohort of pregnant women. Aiming to extrapolate to pathological conditions, this invaluable "human model" allowed us to demonstrate that arterial hypertension is a critical CVR for worse RR and that ST2/IL33-receptors and CRP are potential biomarkers of postpartum hypertrophy reversal.

Isovolumic Contraction Velocity in Heart Failure With Reduced Ejection Fraction and Effect of Sacubitril/Valsartan: the PROVE-HF Study.

OBJECTIVES: To assess tissue Doppler-derived mitral annular isovolumic contraction velocity (ICV) after starting sacubitril/valsartan (sac/val) for the treatment of heart failure with reduced ejection fraction (HFrEF) and left ventricular [LV] EF < 40%). BACKGROUND: ICV may inform load-independent systolic function; combining ICV and LVEF may improve assessment of LV contractility. METHODS: Among 651 participants with HFrEF treated with sac/val, echocardiograms were performed at baseline, 6 and 12 months. Pretreatment median ICVs and LVEFs were used for classification to predict LV reverse remodeling, health status using the Kansas City Cardiomyopathy Questionnaire, and biomarker concentrations. RESULTS: The mean age was 64.6 ± 12.4 years, and 28% were women, baseline LVEF: 28.9% ± 6.9%. Compared to baseline, median ICV increased post sac/val therapy (4.6 [3.5, 6.1] vs 4.9 [3.6, 6.4]; P = 0.005). ICV added value to separate and combined models of biomarkers and clinical and echocardiographic variables for prediction of post-therapy EF recovery. Classification using baseline ICV/EF yielded relatively equal numbers in 4 groups based on low/high ICV or LVEF. Most deleterious results for remodeling, health status and biomarkers were found in patients with low ICV/low EF, whereas patients with high ICV/high EF had the best profiles; other groups were intermediate. Significant shifts toward better ICV/EF profiles were noted post sac/val treatment compared to baseline, with doubling of high ICV/high EF (241 [60%] vs 123 [31%]) and 78% reduction of low ICV/low EF (28 [7%] vs 125 [32%]). CONCLUSIONS: In HFrEF, ICV adds to the profiling of systolic function and represents an independent predictor of reverse cardiac remodeling after treatment with sac/val. ICV changes may be used for assessment of treatment responses.

Early reverse remodeling of left heart morphology and function evaluated by cardiac magnetic resonance in hypertrophic obstructive cardiomyopathy after transapical beating-heart septal myectomy.

PURPOSE: This study aimed to evaluate the early morphology and function of the left heart in hypertrophic obstructive cardiomyopathy (HOCM) after transapical beating-heart septal myectomy (TA-BSM) using cardiovascular magnetic resonance (CMR). MATERIALS AND METHODS: Between April 2022 and January 2023, HOCM patients who underwent CMR before and 3 months after TA-BSM were prospectively and consecutively enrolled in the study. Preoperative and postoperative cardiac morphological and functional parameters, including those for the left atrium (LA) and left ventricle (LV), were compared. The left ventricular remodeling index (LVRI) was defined as the ratio between left ventricular mass (LVM) and left ventricular end-diastolic volume (LVEDV). Healthy participants with a similar age and sex distribution were enrolled for comparison. Pearson or Spearman correlation analysis was used to investigate the relationships between the parameters and LVRI. Last, univariate and multivariate linear regression identified variables associated with the LVM index (LVMI) and LVRI. RESULTS: Forty-one patients (mean age ± standard deviation, 46 ± 2 years; 27 males) and 41 healthy control participants were evaluated. Eighteen (44%) HOCM patients were classified as having a sigmoid septum, and 23 patients had a reverse septal curvature. LA volume, diameter and function were significantly improved postoperatively, but still worse than healthy controls (all p < 0.001). Compared to before the operation, left ventricular wall thickness, left ventricular ejection fraction (LVEF), LVMI, and LVRI decreased after TA-BSM (all p < 0.001). The left ventricular end-diastolic volume index (LVEDVI) and left ventricular end-diastolic diameter (LVEDD) decreased in patients with a sigmoid septum. However, LVEDVI and LVEDD increased in those with a reverse septal curvature (both p < 0.001). In addition, both preoperative and postoperative LVRI was positively correlated with LVMI (r = 0.734 and 0.853, both p < 0.001) and maximum wall thickness (r = 0.679 and 0.676, both p < 0.001), respectively. In the multivariable analysis, the weight of the resected myocardium (adjusted ß = 0.476, p = 0.005) and △mitral regurgitation degree (adjusted ß = - 0.245, p = 0.040) were associated with △LVRI. Last, the △LVOTG (adjusted ß = 0.436, p = 0.018) and baseline LVMI (adjusted ß = 0.323, p = 0.040) were independently associated with greater left ventricular mass regression after TA-BSM. CONCLUSION: CMR confirmed early reverse remodeling of left heart morphology and function in HOCM patients following TA-BSM.

Concomitant aortic regurgitation predicts better left ventricular reverse remodeling after transcatheter aortic valve replacement.

BACKGROUND: We aim to determine predictors of inadequate left ventricular mass index (LVMi) regression at mid-term after transcatheter aortic valve replacement (TAVR), including the potential role of epicardial adipose tissue (EAT). METHODS: We retrospectively reviewed patients with both echocardiographic assessments and multi-slice computed tomography (MSCT) obtained one year after TAVR. The change of LVMi, the volume and the average CT attenuation of EAT from baseline to one-year follow-up was calculated. Patients were divided into two groups by the percentage change of LVMi at a cut-off of 15%. RESULTS: A total of 152 patients were included with a median age of 74 years (interquartile range [IQR] 69-78 years) and 56.6% being male. LVMi decreased (P < 0.0001) while EAT volume increased and the average CT attenuation decreased (both P < 0.0001) at one year. Baseline atrial fibrillation (P = 0.042), mitral regurgitation ≥ mild (P = 0.006), aortic regurgitation (AR) > mild (P = 0.001) and the change in the average CT attenuation of EAT (P = 0.026) were different between the decrease of LVMi ≥ 15% and < 15%. AR > mild at baseline was the only statistically significant predictor of a decrease of LVMi < 15% at one year (OR 0.33, 95% CI: 0.13 to 0.84, P = 0.021) in multivariate regression. CONCLUSIONS: Concomitant more-than-mild AR might predict better left ventricular reverse remodeling regression after TAVR.

Efficacy of Doppler echocardiography-guided ivabradine therapy.

BACKGROUND: 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. METHODS: 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. RESULTS: A total of 28 patients (62 years 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). CONCLUSIONS: 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.

A new composite indicator consisting of left ventricular extracellular volume, N-terminal fragment of B-type natriuretic peptide, and left ventricular end-diastolic volume is useful for predicting reverse remodeling after catheter ablation for atrial fibrillation.

Recently, myocardial extracellular volume (ECV) analysis has been measurable on computed tomography (CT) using new software. We evaluated the use of cardiac CT to estimate the myocardial ECV of left ventricular (LV) myocardium (LVM) to predict reverse remodeling (RR) in cases of atrial fibrillation (AF) after catheter ablation (CA). Four hundred and seven patients underwent CA for AF in our institution from April 2014 to Feb 2021. Of these, 33 patients (8%) with an LVEF ≤ 50% and who had undergone CT were included in our study. We estimated the LVM ECV using commercial software to analyze the CT data. RR was defined as an improvement in LVEF to > 50% after CA. LVEF increased to > 50% in 24 patients (73%) after CA. In all 24 patients, LVM ECV, LV end-diastolic and end-systolic volumes (LVEDV and LVESV), and the n-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) were significantly lower than in the other nine patients (P = 0.0037, 0.0273, 0.0443, and < 0.0001). On receiver operating characteristic curve analysis, the best cut-off of ECV, LVEDV, LVESV and NT-proBNP for the prediction of RR were 37.73%, 120 mL, 82 mL, and 1267 pg/mL, respectively. We newly defined the ENL (ECV, NT-proBNP, and LVEDV) score as the summed score for the presence or absence (1 or 0; maximum score = 3) of ECV, NT-proBNP, and LVEDV values less than or equal to each best cut-off value, and found that this score gave the highest area under the curve for the prediction of RR (0.9583, P < 0.0001). The ENL score may be useful for predicting RR in patients with AF undergoing CA.

Medical Management of Right Ventricular Dysfunction in Pulmonary Arterial Hypertension.

PURPOSE OF REVIEW: The purpose of this review is to overview the most relevant and recent knowledge regarding medical management in pulmonary arterial hypertension (PAH). RECENT FINDINGS: Evidence has shown that PAH patients' quality of life and prognosis depend on the capability of the RV to adapt to increased afterload and to fully recover in response to substantially reduced pulmonary vascular resistance obtained with medical therapy. Data from recent clinical studies show that more aggressive treatment strategies, especially in higher risk categories, determine larger afterload reductions, consequentially increasing the probability of achieving right heart reverse remodeling, therefore improving the patients' survival and quality of life. Remarkable progress has been observed over the past decades in the medical treatment of PAH, related to the development of drugs that target multiple biological pathways, strategies for earlier and more aggressive treatment interventions. New hopes for treatment of patients who are unable to achieve low-risk status have been derived from the phase 2 trial PULSAR and the phase 3 trial STELLAR, which show improvement in the hemodynamic status of patients treated with sotatercept on top of background therapy. Promising results are expected from several ongoing clinical trials targeting new pathways involved in the pathophysiology of PAH.

Outcome for concomitant mitral regurgitation after surgery for aortic insufficiency.

BACKGROUND: Moderate/severe aortic regurgitation (AR) with concomitant mitral regurgitation (MR) is a common multiple valve disease for which treatment strategies are controversial. The current study explored long-term outcomes of concomitant MR after AR surgery and the effect of combined mitral valvuloplasty. METHODS: A total of 506 patients with moderate/severe AR and concomitant MR undergoing aortic valve surgery between January 2013 and December 2021 in our cardiac center were enrolled. Risk factors for early mortality, late mortality and persistent MR were identified by logistic regression and generalized linear mixed model. RESULTS: At least one follow-up record was available for 96.3% patients up to May 2022 and 264 (66.8%) patients had no or trivial MR, 112 (28.4%) had mild MR, 16 (4.1%) had moderate MR and 3 (0.8%) patients had severe MR. Persistent MR was recorded for 92 (23.3%) patients during follow-up. Combined mitral valvuloplasty (odds ratio: 0.23; 95% confidential interval: 0.08-0.64; p = 0.005) and better left ventricular reverse remodeling (odds ratio: 0.99; 95% confidential interval: 0.986-0.996); p < 0.001) were found likely to reduce the possibility of persistent MR during follow-up. CONCLUSIONS: Most patients with moderate/severe AR and concomitant MR had a good long-term post-surgical outcome for MR. However, a few had persistent MR during follow-up. Combined mitral valvuloplasty and better left ventricular reverse remodeling reduced the possibility of long-term persistent MR.

Left ventricular reverse remodeling after transcatheter aortic valve replacement for predominant aortic stenosis and mixed aortic valve disease.

BACKGROUND: Mixed aortic valve disease (MAVD) is a frequent concomitant valve disease with unique cardiac pathological changes compared to predominant aortic stenosis (PAS). The previous studies about the MAVD are contradictory. Therefore, a new perspective is needed to assess the value of TAVR for this cohort of patients. METHODS: From January 2018 to December 2021, 90 MAVD patients and 72 PAS patients who underwent TAVR in our hospital were collected. 1:1 propensity score matching analysis was used to control the bias in patient selection. The dynamic changes in left ventricular morphology and hemodynamics were compared by generalized estimating equations. Univariate or multivariate logistic regression analysis was used to screen for independent risk factors for the non-occurrence of left ventricular reverse remodeling (non-LVRR). RESULTS: After the matching procedure, 112 patients were included in the analysis (56 in each group). Baseline characteristics were similar between the two groups. LVRR occurred in both groups, but MAVD had greater left ventricular end-diastolic volume index and left ventricular mass index, a higher incidence of mitral regurgitation (MR), and a more pronounced transformation of ventricular geometry patterns. Post-operative MR (odd ratio [OR]: 10.05; 95% confidence interval [CI]: 2.08-48.57; p < .001) and coronary artery disease (OR: 2.82; 95% CI: 1.08-7.34; p = .034) were independent risk factors for non-LVRR. CONCLUSION: LVRR also occurs in patients with MAVD, post-operative MR and coronary artery disease were independent risk factors for non-LVRR.

Sizing SGLT2 Inhibitors Up: From a Molecular to a Morpho-Functional Point of View.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), or gliflozins, have recently been shown to reduce cardiovascular death and hospitalization in patients with heart failure, representing a revolutionary therapeutic tool. The purpose of this review is to explore their multifaceted mechanisms of actions, beyond their known glucose reduction power. The cardioprotective effects of gliflozins seem to be linked to the maintenance of cellular homeostasis and to an action on the main metabolic pathways. They improve the oxygen supply for cardiomyocytes with a considerable impact on both functional and morphological myocardial aspects. Moreover, multiple molecular actions of SGLT2i are being discovered, such as the reduction of both inflammation, oxidative stress and cellular apoptosis, all responsible for myocardial damage. Various studies showed controversial results concerning the role of SGLT2i in reverse cardiac remodeling and the lowering of natriuretic peptides, suggesting that their overall effect has yet to be fully understood. In addition to this, advanced imaging studies evaluating the effect on all four cardiac chambers are lacking. Further studies will be needed to better understand the real impact of their administration, their use in daily practice and how they can contribute to benefits in terms of reverse cardiac remodeling.

Combined Left Ventricular Ejection Fraction and N-Terminal pro-B-type Natriuretic Peptide after Sacubitril/Valsartan for Predicting Outcomes in Patients with Heart Failure with Reduced Ejection Fraction.

Background: The aim of this study was to determine whether a combined increase of ≥ 10% in left ventricular ejection fraction (LVEF) and decrease in N-terminal pro-B-type natriuretic peptide (NT pro-BNP) to < 1000 pg/mL after treatment with sacubitril/valsartan (SAC/VAL) in patients with heart failure with reduced ejection fraction (HFrEF) translated to better treatment outcomes in a real-world Taiwanese population. Methods: This is a single-center, prospective, non-randomized, observational study. Consecutive patients with HFrEF were treated with SAC/VAL and followed up for at least 12 months. The primary endpoint was a change in LVEF and reduction in NT pro-BNP at 12 months. The secondary outcomes were death and heart failure (HF) rehospitalization. Results: A total of 105 patients were analyzed after 12 months of SAC/VAL treatment. The mean age was 66.0 ± 11.6 years, and the mean LVEF and NT pro-BNP were 33.6 ± 6.7% and 4462.7 ± 5851.7 pg/mL respectively. The mean LVEF significantly increased to 50.5 ± 10.3% (p < 0.001), while NT pro-BNP decreased to 1270.3 ± 2368.2 pg/mL (p = 0.001) at 12 months, with the greatest changes occurring in the first 3 months of treatment (p < 0.001). Five patients died and 12 were rehospitalized for HF. None of the patients in the responder group died compared to 5 deaths in the non-responder group (p = 0.039). Combined ≥ 10% LVEF increase and NT pro-BNP of < 1000 pg/mL was an independent predictor of death and HF rehospitalization (p = 0.019). Conclusions: SAC/VAL treatment resulted in significant improvements in LVEF, reduced NT pro-BNP level, death and HF hospitalization. Taken separately, an NT pro-BNP level of < 1000 pg/mL was a better predictor than ≥ 10% LVEF increase. Combining both variables predicted fewer deaths and HF rehospitalizations. Even with failure to reach the target dose, SAC/VAL still had significantly beneficial treatment outcomes in Taiwanese patients.