Obesity: the perfect storm for heart failure.

Obesity condition causes morphological and functional alterations involving the cardiovascular system. These can represent the substrates for different cardiovascular diseases, such as atrial fibrillation, coronary artery disease, sudden cardiac death, and heart failure (HF) with both preserved ejection fraction (EF) and reduced EF. Different pathogenetic mechanisms may help to explain the association between obesity and HF including left ventricular remodelling and epicardial fat accumulation, endothelial dysfunction, and coronary microvascular dysfunction. Multi-imaging modalities are required for appropriate recognition of subclinical systolic dysfunction typically associated with obesity, with echocardiography being the most cost-effective technique. Therapeutic approach in patients with obesity and HF is challenging, particularly regarding patients with preserved EF in which few strategies with high level of evidence are available. Weight loss is of extreme importance in patients with obesity and HF, being a primary therapeutic intervention. Sodium-glucose co-transporter-2 inhibitors have been recently introduced as a novel tool in the management of HF patients. The present review aims at analysing the most recent studies supporting pathogenesis, diagnosis, and management in patients with obesity and HF.

Role of Multi-parameter-based Cardiac Magnetic Resonance in the Evaluation of Patients with Coronary Heart Disease Combined with Heart Failure.

BACKGROUND: Coronary Heart Disease (CHD) is one of the most common types of cardiovascular disease, and Heart Failure (HF) is an important factor in its progression. We aimed to evaluate the diagnostic value and predictors of multiparametric Cardiac Magnetic Resonance (CMR) in CHD patients with HF. METHODS: The study retrospectively included 145 CHD patients who were classified into CHD (HF+) (n = 91) and CHD (HF-) (n = 54) groups according to whether HF occurred. CMR assessed LV function, myocardial strain and T1 mapping. Multivariate linear regression analyses were performed to identify predictors of LV dysfunction, myocardial fibrosis, and LV remodeling. RESULTS: CHD (HF+) group had impaired strain, with increased native T1, ECV, and LVM index. The impaired strain was associated with LVM index (p < 0.05), where native T1 and ECV were affected by log-transformed amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. ROC analysis showed the combination of global circumferential strain (GCS), native T1, and LVM had a higher diagnostic value for the occurrence of HF in CHD patients.

Meanwhile, log-transformed NT-proBNP was an independent determinant of impaired strain, increased LVM index, native T1 and ECV. CONCLUSION: HF has harmful effects on LV systolic function in patients with CHD. In CHD (HF+) group, LV dysfunction is strongly correlated with the degree of LV remodeling and myocardial fibrosis. The combination of the three is more valuable in diagnosing HF than conventional indicators.

Study on the mechanism underlying Trichosanthis peel injection-induced improvements in myocardial fibrosis markers in patients with chronic heart failure.

In this research, we aimed to observe the changes in myocardial fibrosis indices in patients with chronic heart failure before and after treatment and to evaluate the anti-chronic heart failure and ventricular remodelling effects of Trichosanthis peel (TP) injection. This study was a single-center, open, single-blind, randomized controlled study with an optimal efficacy design. Patients were consecutively and randomly divided into two groups, with 36 patients in the TP injection group and 36 patients in the conventional treatment group. ELISA was used to measure changes in myocardial fibrosis indices before and after discharge, including transforming growth factor ß (TGF-ß), serum hyaluronic acid (HA), type I procollagen (PCI), laminin (LN) and type III procollagen (PCIII). There was no significant difference between the two groups in clinical data or baseline level of myocardial fibrosis before treatment. After treatment, compared with the conventional treatment group, the myocardial fibrosis index was significantly decreased following TP injection. Our findings indicate that TP injection combined with conventional medicine can attenuate myocardial fibrosis by reducing angiotensin II, aldosterone, TGFß, HA, PCI, metallomatrix proteinase 2, connective tissue growth factor and LN and promote ventricular remodelling in patients with chronic heart failure.

Effect of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction: a meta-analysis.

Heart failure is the final stage of several cardiovascular diseases, and the key to effectively treating heart failure is to reverse or delay ventricular remodelling. Levosimendan is a novel inotropic and vasodilator agent used in heart failure, whereas the impact of levosimendan on ventricular remodelling is still unclear. This study aims to investigate the impact of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction. Electronic databases were searched to identify eligible studies. A total of 66 randomized controlled trials involving 7968 patients were included. Meta-analysis results showed that levosimendan increased left ventricular ejection fraction [mean difference (MD) = 3.62, 95% confidence interval (CI) (2.88, 4.35), P < 0.00001] and stroke volume [MD = 6.59, 95% CI (3.22, 9.96), P = 0.0001] and significantly reduced left ventricular end-systolic volume [standard mean difference (SMD) = -0.52, 95% CI (-0.67, -0.37), P < 0.00001], left ventricular end-diastolic volume index [SMD = -1.24, 95% CI (-1.61, -0.86), P < 0.00001], and left ventricular end-systolic volume index [SMD = -1.06, 95% CI (-1.43, -0.70), P < 0.00001]. In terms of biomarkers, levosimendan significantly reduced the level of brain natriuretic peptide [SMD = -1.08, 95% CI (-1.60, -0.56), P < 0.0001], N-terminal pro-brain natriuretic peptide [SMD = -0.99, 95% CI (-1.41, -0.56), P < 0.00001], and interleukin-6 [SMD = -0.61, 95% CI (-0.86, -0.35), P < 0.00001]. Meanwhile, levosimendan may increase the incidence of hypotension [risk ratio (RR) = 1.24, 95% CI (1.12, 1.39), P < 0.0001], hypokalaemia [RR = 1.57, 95% CI (1.08, 2.28), P = 0.02], headache [RR = 1.89, 95% CI (1.50, 2.39), P < 0.00001], atrial fibrillation [RR = 1.31, 95% CI (1.12, 1.52), P = 0.0005], and premature ventricular complexes [RR = 1.86, 95% CI (1.27, 2.72), P = 0.001]. In addition, levosimendan reduced all-cause mortality [RR = 0.83, 95% CI (0.74, 0.94), P = 0.002]. In conclusion, our study found that levosimendan might reverse ventricular remodelling when applied in patients with left ventricular systolic dysfunction, especially in patients undergoing cardiac surgery, decompensated heart failure, and septic shock.

[Catheter ablation of atrial fibrillation : Evidence and current techniques]. / Katheterablation von Vorhofflimmern : Evidenz und aktuelle Techniken.

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia with increasing clinical and healthcare economic relevance. A timely treatment prevents or slows the remodelling process of the atrial and ventricular myocardium initiated by AF, emphasizing its relevance especially in heart failure patients. Catheter ablation for the treatment of AF is safe and effective. The three ablation techniques currently used are comparable in terms of success rates but differ in terms of risk profile and the type of lesion formation.

Association of aortic stiffness early post myocardial infarction with left ventricular remodelling.

BACKGROUND: Adverse left ventricular (LV) remodelling after myocardial infarction is associated with heart failure. We investigated whether aortic stiffness during acute ST-segment elevation myocardial infarction is associated with LV remodelling at long-term follow-up. METHODS: In 109 patients within 48 h of myocardial infarction post-primary percutaneous coronary intervention and after 2 years, we measured: (a) carotid to femoral pulse wave velocity (PWV), (b) LV global longitudinal strain (GLS) and left atrial strain using speckle-tracking echocardiography, (c) PWV/GLS ratio as a surrogate marker of ventricular-arterial interaction, and (d) LV end-diastolic and end-systolic volumes. A > 15% decrease from the baseline in LV end-systolic volume at 2-year follow-up was considered as a criterion of reverse LV remodelling. RESULTS: Compared with baseline, all patients had reduced PWV, LV end-diastolic and end-systolic volumes while PWV/GLS, GLS and reservoir left atrial strain were improved (p < .05) after 2 years. Baseline values of PWV, GLS, PWV/GLS ratio and reservoir left atrial strain were associated with percentage change of LV end-systolic volume at 2 years (p < .05). Multivariable analysis revealed that lower baseline values of PWV and a less impaired GLS and PWV/GLS were independently associated with reverse LV remodelling at 2 years with a C-statistic of .748, .711 and .787, respectively. CONCLUSION: Aortic stiffness early post-infarction determines LV remodelling after 2 years of the ischemic event despite post successful revascularization. CLINICAL TRIAL REGISTRATION-URL: http://www. CLINICALTRIALS: gov. Unique identifier: NCT03984123, 30/04/2020.

Activation of AHR by ITE improves cardiac remodelling and function in rats after myocardial infarction.

AIMS: Left ventricular remodelling subsequent to myocardial infarction (MI) constitutes a pivotal underlying cause of heart failure. Intervention with the nontoxic endogenous aryl hydrocarbon receptor (AHR) agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) in the acute phase of MI has been shown to ameliorate cardiac function, but its role in the chronic phase remains obscured. This study explores the beneficial role of ITE in delaying the progression of heart failure in the chronic phase of MI. METHODS AND RESULTS: MI rats established by ligating the left anterior descending coronary artery were treated with the indicated concentration of the AHR agonist ITE or vehicle alone. Echocardiography was performed to determine cardiac structure and function; myocardial morphology and fibrosis were observed by haematoxylin and eosin and Masson's trichrome staining; serum biochemical indices, BNP, and inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay; F4/80+ iNOS+ M1 macrophages and F4/80+ CD206+ M2 macrophages were detected by immunofluorescence; the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay was used to detect the apoptosis of cardiomyocytes; ultrastructural changes in myocardial tissue were observed by transmission electron microscopy; and Cyp1a1, Akt, P-Akt, p70S6K, P-p70S6K, Bcl-2, Bax, caspase-3, and cleaved caspase-3 protein levels were determined via Western blotting. We found that therapy with the AHR agonist ITE rescued cardiac remodelling and dysfunction in rats with MI and attenuated myocardial fibrosis, inflammation, and mitochondrial damage. Further studies confirmed that ITE dose-dependently improved myocardial cell apoptosis after MI, as demonstrated by reduced levels of the apoptosis-related proteins cleaved caspase-3 and Bax but increased expression levels of Bcl-2. These effects were attributed to ITE-induced activation of AHR receptors, leading to the down-regulation of Akt and p70S6K phosphorylation. CONCLUSIONS: The AHR agonist ITE alleviates cardiomyocyte apoptosis through the Akt/p70S6K signalling pathway, thereby rescuing left ventricular adverse remodelling and cardiac dysfunction after MI.

Left ventricular remodelling in rheumatic heart disease - trends over time and implications for follow-up in childhood.

BACKGROUND: Rheumatic heart disease (RHD) is the most common form of acquired heart disease worldwide. In RHD, volume loading from mitral regurgitation leads to left ventricular (LV) dilatation, increased wall stress, and ultimately LV dysfunction. Improved understanding of LV dynamics may contribute to refined timing of intervention. We aimed to characterize and compare left ventricular remodelling between rheumatic heart disease (RHD) severity groups by way of serial echocardiographic assessment of volumes and function in children. METHODS: Children with RHD referred to Perth Children's Hospital (formally Princess Margaret Hospital) (1987-2020) were reviewed. Patients with longitudinal pre-operative echocardiograms at diagnosis, approximately 12 months and at most recent follow-up, were included and stratified into RHD severity groups. Left ventricular (LV) echocardiographic parameters were assessed. Adjusted linear mixed effect models were used to compare interval changes. RESULTS: 146 patients (median age 10 years, IQR 6-14 years) with available longitudinal echocardiograms were analysed. Eighty-five (58.2%) patients had mild, 33 (22.6%) moderate and 28 (19.2%) severe RHD at diagnosis. Mean duration of follow-up was 4.6 years from the initial diagnosis. Severe RHD patients had significantly increased end-systolic volumes (ESV) and end-diastolic volumes (EDV) compared to mild/moderate groups at diagnosis (severe versus mild EDV mean difference 27.05 ml/m2, p < 0.001, severe versus moderate EDV mean difference 14.95 ml/m2, p = 0.006). Mild and moderate groups experienced no significant progression of changes in volume measures. In severe RHD, LV dilatation worsened over time. All groups had preserved cardiac function. CONCLUSIONS: In mild and moderate RHD, the lack of progression of valvular regurgitation and ventricular dimensions suggest a stable longer-term course. Significant LV remodelling occurred at baseline in severe RHD with progression of LV dilatation over time. LV function was preserved across all groups. Our findings may guide clinicians in deciding the frequency and timing of follow-up and may be of clinical utility during further reiterations of the Australia and New Zealand RHD Guidelines.

Reduced Left Ventricular Twist Early after Acute ST-Segment Elevation Myocardial Infarction as a Predictor of Left Ventricular Adverse Remodelling.

BACKGROUND: The left ventricular (LV) remodelling process represents the main cause of heart failure after a ST-segment elevation myocardial infarction (STEMI). Speckle-tracking echocardiography (STE) can detect early deformation impairment, while also predicting LV remodelling during follow-up. The aim of this study was to investigate the STE parameters in predicting cardiac remodelling following a percutaneous coronary intervention (PCI) in STEMI patients. METHODS: The study population consisted of 60 patients with acute STEMI and no history of prior myocardial infarction treated with PCI. The patients were assessed both by conventional transthoracic and ST echocardiography in the first 12 h after admission and 6 months after the acute phase. Adverse remodelling was defined as an increase in LVEDV and/or LVESV by 15%. RESULTS: Adverse remodelling occurred in 26 patients (43.33%). By multivariate regression equation, the risk of adverse remodelling increases with age (by 1.1-fold), triglyceride level (by 1.009-fold), and midmyocardial radial strain (mid-RS) (1.06-fold). Increased initial twist decreases the chances of adverse remodelling (0.847-fold). The LV twist presented the largest area under the receiver operating characteristic (ROC) curve to predict adverse remodelling (AUROC = 0.648; 95% CI [0.506;0.789], p = 0.04). A twist value higher than 11° has a 76.9% specificity and a 72.7% positive predictive value for reverse remodelling at 6 months.

Role of aldosterone in mid- and long-term left ventricular remodelling after acute myocardial infarction: The REMI study.

AIMS: Whether aldosterone levels after myocardial infarction (MI) are associated with mid- and long-term left ventricular (LV) remodelling in the era of systematic use of renin-angiotensin system inhibitors is uncertain. We prospectively investigated the relationship between aldosterone levels and mid- and long-term LV remodelling in patients with acute MI. METHODS AND RESULTS: Plasma aldosterone was measured in 119 patients successfully treated by primary percutaneous coronary angioplasty for a first acute ST-elevation MI (STEMI) 2-4 days after the acute event. LV volumes were assessed by cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE) in the same timeframe and 6 months later. LV assessment was repeated by TTE 3-9 years after MI (n = 80). The median aldosterone level at baseline was 23.1 [16.8; 33.1] pg/ml. In the multivariable model, higher post-MI aldosterone concentration was significantly associated with more pronounced increase in LV end-diastolic volume index (TTE: ß ± standard error [SE]: 0.113 ± 0.046, p = 0.015; CMR: ß ± SE: 0.098 ± 0.040, p = 0.015) and LV end-systolic volume index (TTE: ß ± SE: 0.083 ± 0.030, p = 0.008; CMR: ß ± SE: 0.064 ± 0.032, p = 0.048) at 6-month follow-up, regardless of the method of assessment. This result was consistent also in patients with a LV ejection fraction (LVEF) >40%. The association between baseline plasma aldosterone and adverse LV remodelling did not persist at the 3-9-year follow-up evaluation. CONCLUSION: Aldosterone concentration in the acute phase was associated with adverse LV remodelling in the medium term, even in the subgroup of patients with LVEF >40%, suggesting a potential role of the mineralocorticoid system in post-MI adverse remodelling. Plasma aldosterone was no longer associated with LV remodelling in the long term (NCT01109225).

Blockage of the adenosine A2B receptor prevents cardiac fibroblasts overgrowth in rats with pulmonary arterial hypertension.

Sustained pressure overload and fibrosis of the right ventricle (RV) are the leading causes of mortality in pulmonary arterial hypertension (PAH). Although the role of adenosine in PAH has been attributed to the control of pulmonary vascular tone, cardiac reserve, and inflammatory processes, the involvement of the nucleoside in RV remodelling remains poorly understood. Conflicting results exist on targeting the low-affinity adenosine A2B receptor (A2BAR) for the treatment of PAH mostly because it displays dual roles in acute vs. chronic lung diseases. Herein, we investigated the role of the A2BAR in the viability/proliferation and collagen production by cardiac fibroblasts (CFs) isolated from RVs of rats with monocrotaline (MCT)-induced PAH. CFs from MCT-treated rats display higher cell viability/proliferation capacity and overexpress A2BAR compared to the cells from healthy littermates. The enzymatically stable adenosine analogue, 5'-N-ethylcarboxamidoadenosine (NECA, 1-30 µM), concentration-dependently increased growth, and type I collagen production by CFs originated from control and PAH rats, but its effects were more prominent in cells from rats with PAH. Blockage of the A2BAR with PSB603 (100 nM), but not of the A2AAR with SCH442416 (100 nM), attenuated the proliferative effect of NECA in CFs from PAH rats. The A2AAR agonist, CGS21680 (3 and 10 nM), was virtually devoid of effect. Overall, data suggest that adenosine signalling via A2BAR may contribute to RV overgrowth secondary to PAH. Therefore, blockage of the A2AAR may be a valuable therapeutic alternative to mitigate cardiac remodelling and prevent right heart failure in PAH patients.

The optimal definition and prediction nomogram for left ventricular remodelling after acute myocardial infarction.

AIMS: Left ventricular (LV) remodelling after acute myocardial infarction (AMI) is associated with heart failure and increased mortality. There was no consensus on the definition of LV remodelling, and the prognostic value of LV remodelling with different definitions has not been compared. We aimed to find the optimal definition and develop a prediction nomogram as well as online calculator that can identify patients at risk of LV remodelling. METHODS AND RESULTS: This prospective, observational study included 829 AMI patients undergoing percutaneous coronary intervention from January 2015 to January 2020. Echocardiography was performed within the 48 h of admission and at 6 months after infarction to evaluate LV remodelling, defined as a 20% increase in LV end-diastolic volume (LVEDV), a 15% increase in LV end-systolic volume (LVESV), or LV ejection fraction (LVEF) < 50% at 6 months. The impact of LV remodelling on long-term outcomes was analysed. Lasso regression was performed to screen potential predictors, and multivariable logistic regression analysis was conducted to establish the prediction nomogram. The area under the curve, calibration curve and decision curve analyses were used to determine the discrimination, calibration and clinical usefulness of the remodelling nomogram. The incidences of LV remodelling defined by LVEDV, LVESV and LVEF were 24.85% (n = 206), 28.71% (n = 238) and 14.60% (n = 121), respectively. Multivariable Cox regression models demonstrated that different definitions of LV remodelling were independently associated with the composite endpoint. However, only remodelling defined by LVEF was significantly connected with long-term mortality (hazard ratio = 2.78, 95% confidence interval 1.41-5.48, P = 0.003). Seven variables were selected to construct the remodelling nomogram, including diastolic blood pressure, heart rate, AMI type, stent length, N-terminal pro brain natriuretic peptide, troponin I, and glucose. The prediction model had an area under the receiver operating characteristics curve of 0.766. The calibration curve and decision curve analysis indicated consistency and better net benefit in the prediction model. CONCLUSIONS: LV remodelling defined by LVEDV, LVESV and LVEF were independent predictors for long-term mortality or heart failure hospitalization in AMI patients after percutaneous coronary intervention. However, only remodelling defined by LVEF was suitable for predicting all-cause death. In addition, the nomogram can provide an accurate and effective tool for the prediction of postinfarct remodelling.

Effect of insulin resistance on left ventricular remodelling in essential hypertensives: a cross-sectional study.

BACKGROUND: In clinical practice, left ventricular hypertrophy (LVH) is defined by physical findings and electrocardiographic criteria, which are useful but imperfect tools, echocardiographic criteria and cardiac magnetic resonance imaging. In echocardiography, LVH is defined not by left ventricular wall thicknesses but by left ventricular mass. The latter is calculated according to Devereux's formula, and is increased by insulin resistance/hyperinsulinaemia. It is however unclear whether insulin resistance, hyperinsulinaemia, or both, is actually causative and what their collective or individual influence is on the components of Devereux's formula and parameters of left ventricular diastolic function. This study evaluated the associations of the homeostatic model assessment for insulin resistance (HOMAIR) and fasting plasma insulin levels with components of Devereux's formula and parameters of left ventricular diastolic function. METHODS: Relevant clinical data were collected from 220 hypertensive patients recruited between January and December 2019. The associations of components of Devereux's formula and parameters of diastolic function with insulin resistance were tested using binary ordinal, conditional and classical logistic regression models. RESULTS: Thirty-two (14.5%) patients (43.9 ± 9.1 years), 99 (45%) patients (52.4 ± 8.7 years) and 89 (40.5%) patients (53.1 ± 9.8 years) had normal left ventricular geometry, concentric left ventricular remodelling and concentric left ventricular hypertrophy, respectively. In multivariable adjusted analysis, 46.8% of variation in interventricular septum diameter (R² = 0.468; overall p = 0.001) and 30.9% of E-wave deceleration time (R² = 0.309; overall p = 0.003) were explained by insulin level and HOMAIR, 30.1% of variation in left ventricular end-diastolic diameter (R² = 0.301; p = 0.013) by HOMAIR alone, and 46.3% of posterior wall thickness (R² = 0.463; p = 0.002) and 29.4% of relative wall thickness (R² = 0.294; p = 0.007) by insulin level alone. CONCLUSIONS: Insulin resistance and hyperinsulinaemia did not have the same influence on the components of Devereux's formula. Insulin resistance appeared to act on left ventricular end-diastolic diameter, while hyperinsulinaemia affected the posterior wall thickness. Both abnormalities acted on the interventricular septum and contributed to diastolic dysfunction via the E-wave deceleration time.

Four- to seven-year follow-up of pharmacological postconditioning with mangafodipir as an adjunct to primary PCI in ST-segment elevation myocardial infarction.

INTRODUCTION: Adverse left ventricular remodelling (AR) develops over time in approximately 30% of patients with a history of coronary artery disease. AR manifests as a structural change in the left ventricle (LV) in terms of increased volumes and reduced left ventricular ejection fraction (LVEF). Manganese dipyridoxyl diphosphate (mangafodipir) has demonstrated interesting cardioprotective features in acute myocardial ischaemia. Pharmacological postconditioning (PP) with mangafodipir as an adjunct to primary percutaneous coronary intervention may possibly reduce the development of AR over time in ST-elevation myocardial infarction (STEMI). The aim of this 4-7-year follow-up study is to investigate the potential benefits of PP with mangafodipir in STEMI patients. METHOD: Thirteen out of the initial 20 patients that were included in the primary study of Karlsson et al. were followed up between April and June 2017. The study group underwent review of the hospital records, a clinical examination with ECG and blood sample analysis before cardiac magnetic resonance examination of the patient. LVEF, left ventricular diastolic volume, left ventricular end systolic volume, LV mass and myocardial strain in all directions were computed. RESULTS: The PP group showed a decrease in LV volume, mass and higher LVEF at follow-up (p < 0.05) while the individual response of the placebo group showed features that are seen in AR. Although there was no difference in myocardial strain, measurement for the PP-group was higher in absolute terms. CONCLUSION: Pharmacological postconditioning with mangafodipir in STEMI demonstrated cardioprotective features compared to the placebo group at follow-up. This article is protected by copyright. All rights reserved.

The saga of dyssynchrony imaging: Are we getting to the point.

Cardiac resynchronisation therapy (CRT) has an established role in the management of patients with heart failure, reduced left ventricular ejection fraction (LVEF < 35%) and widened QRS (>130 msec). Despite the complex pathophysiology of left ventricular (LV) dyssynchrony and the increasing evidence supporting the identification of specific electromechanical substrates that are associated with a higher probability of CRT response, the assessment of LVEF is the only imaging-derived parameter used for the selection of CRT candidates. This review aims to (1) provide an overview of the evolution of cardiac imaging for the assessment of LV dyssynchrony and its role in the selection of patients undergoing CRT; (2) highlight the main pitfalls and advantages of the application of cardiac imaging for the assessment of LV dyssynchrony; (3) provide some perspectives for clinical application and future research in this field. Conclusion: the road for a more individualized approach to resynchronization therapy delivery is open and imaging might provide important input beyond the assessment of LVEF.

Dose titration of sacubitril/valsartan for heart failure with reduced ejection fraction: a real-world study.

AIMS: The study aims to explore the real-world titration patterns of sacubitril/valsartan in a chronic heart failure (HF) follow-up management system and the effect on the recovery of ventricular remodelling and cardiac function in China. METHODS AND RESULTS: This is a single-centre, observational study of 153 adult outpatients with HF and reduced ejection fraction who were managed in the chronic HF follow-up management system and prescribed with sacubitril/valsartan from August 2017 to August 2021 in China. All patients tried to titrated sacubitril/valsartan to the tolerant dose during follow-up. The primary outcome was the proportion of patients who reached and maintained the target dose of sacubitril/valsartan. The main secondary outcomes were the changes in left atrium diameter, left ventricular end-diastolic diameter (LVEDD), and left ventricular ejection fraction (LVEF) from baseline to 12 months. Among the patients, 69.3% were male, with a median age of 49 years. The baseline systolic blood pressure (SBP) was 117.6 ± 18.3 mmHg before starting the treatment of sacubitril/valsartan. Benefiting from the management system, 117 (76.5%) patients achieved the target dose of sacubitril/valsartan, and the median time to reach the target dose was 3 (IQR 1-5) months. Advanced age and lower SBP may be predictors of failure to reach the target dose. Compared with baseline, standard treatment resulted in a pronounced improvement in left ventricular geometry and cardiac function. The patients showed a significant increase in LVEF [28 (IQR 21-34) % vs. 42 (IQR 37.0-54.3) %, P < 0.001], with a great reduction in left atrium diameter [45 (IQR 40.3-51.0) mm vs. 41 (IQR 37.0-45.3) mm, P < 0.001] and LVEDD [65 (IQR 60.0-70.3) mm vs. 55 (IQR 52-62) mm, P < 0.001] during 12 month follow-up. Of patients, 36.5% had a LVEF ≥50%, 54.1% had LVEF >40%, and 81.1% experienced an increase in LVEF of ≥10%. After 12 month follow-up, the proportion of patients with New York Heart Association classification I or II increased from 41.8% to 96.4%. Additionally, there was a significant improvement in N-terminal pro-B-type natriuretic peptide (P < 0.001). At Month 12, 50% of patients achieved the target dose of beta-blockers. No serious adverse events caused by sacubitril/valsartan were observed during the follow-up. CONCLUSIONS: Optimising HF follow-up management was essential and effective in a real-world clinical setting; the majority could reach the target dose of sacubitril/valsartan within the management system and achieve a remarkable improvement in cardiac function and ventricular remodelling.

Use of serial changes in biomarkers vs. baseline levels to predict left ventricular remodelling after STEMI.

AIMS: Cellular communication network factor 1 (CCN1) is an independent predictor of MACE after ACS and elevated levels correlated with infarct size after STEMI. We compared the prognostic accuracy of baseline levels of CCN1, NT-proBNP, hsTnT, and ST2 and changes in levels over time to predict the development of structural and functional alterations typical of LV remodelling. METHODS: Serial 3-T cMRI scans were performed to determine LVEF, LVEDV, LVESV, infarct size, and relative infarct size, which were correlated with serial measurements of the four biomarkers. The prognostic significance of these biomarkers was assessed by multiple logistic regression analysis by examining their performance in predicting dichotomized cardiac MRI values 12 months after STEMI based on their median. For each biomarker three models were created using baseline (BL), the Δ value (BL to 6 months), and the two values together as predictors. All models were adjusted for age and renal function. Receiver operator curves were plotted with area under the curve (AUC) to discriminate the prognostic accuracy of individual biomarkers for MRI-based structural or functional changes. RESULTS: A total of 44 predominantly male patients (88.6%) from the ETiCS (Etiology, Titre-Course, and Survival) study were identified at a mean age of 55.5 ± 11.5 (SD) years treated by successful percutaneous coronary intervention (97.7%) at a rate of 95.5% stent implantation within a median pain-to-balloon time of 260 min (IQR 124-591). Biomarkers hsTnT and ST2 were identified as strong predictors (AUC > 0.7) of LVEDV and LVEF. BL measurement to predict LVEF [hsTnT: AUC 0.870 (95% CI: 0.756-0.983), ST2: AUC 0.763 (95% CI: 0.615-0.911)] and the Δ value BL-6M [hsTnT: AUC 0.870 (95% CI: 0.756-0.983), ST2: AUC 0.809 (95% CI: 0.679-0.939)] showed a high prognostic value without a significant difference for the comparison of the BL model vs. the Δ-value model (BL-6M) for hsTnT (P = 1) and ST2 (P = 0.304). The combined model that included baseline and Δ value as predictors was not able to improve the ability to predict LVEF [hsTnT: AUC 0.891 (0.791-0.992), P = 0.444; ST2: AUC 0.778 (0.638-0.918), P = 0.799]. Baseline levels of CCN1 were closely associated with LVEDV at 12 months [AUC 0.708 (95% CI: 0.551-0.865)] and infarct size [AUC 0.703 (95% CI: 0.534-0.872)]. CONCLUSIONS: Baseline biomarker levels of hsTnT and ST2 were the strongest predictors of LVEF and LVEDV at 12 months after STEMI. The association of CCN1 with LVEDV and infarct size warrants further study into the underlying pathophysiology of this novel biomarker.

Prognostic value of right ventricular remodelling in patients undergoing concomitant aortic and mitral valve surgery.

AIMS: Long-term risk stratification and surgical timing remain suboptimal in concomitant aortic and mitral (double) valve surgery. This study sought to examine the predictors, changes, and prognostic implications of right ventricular (RV) remodelling in patients undergoing double-valve surgery. METHODS AND RESULTS: In 152 patients undergoing double-valve surgery, four RV remodelling patterns were characterized using transthoracic echocardiography: normal RV size and systolic function (Pattern 1); dilated RV (tricuspid annulus diameter >35 mm) with normal systolic function (Pattern 2); normal RV size with systolic dysfunction (percentage RV fractional area change <35%; Pattern 3); and dilated RV with systolic dysfunction (Pattern 4). The primary endpoint was the composite of heart failure hospitalization and all-cause mortality. Patterns 1, 2, 3, and 4 RV remodelling were present in 41, 20, 23, and 16% of patients, respectively. Patients with Stage 4 RV remodelling had worse renal function, higher EuroSCORE II, and impaired left ventricular ejection fraction. During a 3.7-year median follow up, 45 adverse events occurred. Patterns 3 and 4 RV remodelling were associated with significantly higher adverse event rates compared with Pattern 1 (37 and 75% vs. 11%, P < 0.01) and had incremental prognostic value when added to clinical parameters and EuroSCORE II (χ2 increased from 30 to 66, P < 0.01). At 1 year after surgery (n = 100), Patterns 3 and 4 RV remodelling had a higher risk of adverse events compared with Pattern 1. CONCLUSION: Right ventricular remodelling was strongly related to adverse outcomes and deserves consideration as part of the risk and decision-making algorithms in double-valve surgery.

Left ventricular anatomy in obstructive hypertrophic cardiomyopathy: beyond basal septal hypertrophy.

AIMS: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by dynamic obstruction of the left ventricular (LV) outflow tract (LVOT). Although this may be mediated by interplay between the hypertrophied septal wall, systolic anterior motion of the mitral valve, and papillary muscle abnormalities, the mechanistic role of LV shape is still not fully understood. This study sought to identify the LV end-diastolic morphology underpinning oHCM. METHODS AND RESULTS: Cardiovascular magnetic resonance images from 2398 HCM individuals were obtained as part of the NHLBI HCM Registry. Three-dimensional LV models were constructed and used, together with a principal component analysis, to build a statistical shape model capturing shape variations. A set of linear discriminant axes were built to define and quantify (Z-scores) the characteristic LV morphology associated with LVOT obstruction (LVOTO) under different physiological conditions and the relationship between LV phenotype and genotype. The LV remodelling pattern in oHCM consisted not only of basal septal hypertrophy but a combination with LV lengthening, apical dilatation, and LVOT inward remodelling. Salient differences were observed between obstructive cases at rest and stress. Genotype negative cases showed a tendency towards more obstructive phenotypes both at rest and stress. CONCLUSIONS: LV anatomy underpinning oHCM consists of basal septal hypertrophy, apical dilatation, LV lengthening, and LVOT inward remodelling. Differences between oHCM cases at rest and stress, as well as the relationship between LV phenotype and genotype, suggest different mechanisms for LVOTO. Proposed Z-scores render an opportunity of redefining management strategies based on the relationship between LV anatomy and LVOTO.

Cardiac magnetic resonance predictors of left ventricular remodelling following acute ST elevation myocardial infarction: The VavirimS study.

BACKGROUND: Left ventricular (LV) remodelling (REM) ensuing after ST-elevation myocardial infarction (STEMI), has typically been studied by echocardiography, which has limitations, or cardiac magnetic resonance (CMR) in early phase that may overestimate infarct size (IS) due to tissue edema and stunning. This prospective, multicenter study investigated LV-REM performing CMR in the subacute phase, and 6 months after STEMI. METHODS AND RESULTS: patients with first STEMI undergoing successful primary angioplasty were consecutively enrolled. CMR was done at 30-days and 6-months. Primary endpoint was prevalence at 6 months of LV-REM [≥12% increase in LV end-diastolic volume index (LV-REMEDV)]; LV-REM by end-systolic volume index increase ≥12% (LV-REMESV) was also calculated. Of 325 patients enrolled, 193 with a full set of research-quality CMR images were analyzed. LV-REMEDV and LV-REMESV were present in 36/193 (19%) and 34/193 (18%) patients, respectively. At follow up, LV ejection fraction (EF) improved in patients with or without LV-REMEDV, whilst it decreased in those with LV-REMESV (p < 0.001 for interaction). Considering predictors of LV-REM, IS in the highest tertile was clearly separated from the two lower tertiles. In LV-REMEDV, the highest tertile was associated with significantly higher LV-EDV, LV-ESV, and lower EF. CONCLUSIONS: In a contemporary cohort of STEMI patients studied by CMR, prevalence of LV-REMEDV was lower than previously reported. Importantly, our data indicate that LV-REMEDV might not be "adverse" per se, but rather "compensatory", being associated with LV-EF improvement at follow-up. Conversely, LV-REMESV might be an "adverse" phenomenon associated with decreased LV-EF, driven by IS.