Left Ventricular End-diastolic Volume Research Articles

Preprocedural global myocardial work index independently predicts NT-proBNP in patients undergoing transcatheter aortic valve replacement: a prospective study

Abstract Global myocardial work index is a novel echocardiographic parameter of the left ventricular (LV) function, which may overcome the load-sensitvity of the traditional functional measures by measuring LV deformation in the context of simultaneous pressures. This approach may gain particular importance in pressure overload states, such as patients with severe aortic stenosis. However, the longitudinal changes of this recently introduced measure are scarcely investigated in this population, and data are also lacking about its association with functional improvement following transcatheter aortic valve replacement (TAVR). Accordingly, our aim was to investigate the clinical determinants of preoperative and also postoperative GMWI in patients undergoing TAVR. Eighty-four patients (54%% male, age: 79±6 years) were enrolled. Prior to the procedure, subjects underwent echocardiographic investigation and the detailed medical history was also recorded. Serum NT-proBNP levels were also measured. We calculated LV ejection fraction and LV end-diastolic volume (EDV), and speckle-tracking analysis was performed to measure global longitudinal strain (GLS). As an accepted method of its estimation, LV pressure curve was generated by adding the mean aortic valve gradient to the systolic blood pressure. Using these measures, global myocardial work index (GMWI) was quantified by commercially available software. 12 months after the procedure, the patients underwent a follow-up echocardiographic examination, and at that time point we determined the same measures. At follow-up, GLS has significantly increased (-13.5±4.5 vs. -15.2±3.6%; p<0.001), while GMWI was significantly lower at the follow-up assessment (1913±786 vs. 1666±594 mmHg%, p<0.01). Compared to the preoperative values, LVEDV also showed a significant decrease at follow-up (115±46 vs. 105±41 mL, p<0.01). Using multivariable analysis, atrial fibrillation (β=0.36; p<0.001) ischemic heart disease (β=0.20; p<0.05) and also GMWI (β=-0.22; p<0.05) were found to be independent predictors of the postoperative NT-proBNP (R2=0.36; overall p<0.001). Importantly, by replacing GMWI to GLS, the latter did not enter the model as a predictor (β=0.17, p=0.11). TAVR significantly alters LV functional and morphological measures. Regarding the functional outcome of the patients, different clinical factors influence NT-proBNP after the procedure. Possibly due to its significant load dependency, preoperative GLS failed to predict NT-proBNP at follow-up, while GMWI was an independent precictor of NT-proBNP at follow up along with atrial fibrillation and ischemic heart disease. GMWI may serve as a useful imaging marker of preprocedural patient assessment before TAVR.

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

Abstract Background Sacubitril/valsartan has become an important first-line drug for symptomatic heart failure (HF) patients, especially with left ventricular (LV) ejection fraction (LVEF) < 50%. Since sacubitril/valsartan was reported to be more potent than renin-angiotensin-aldosterone system inhibitors for lowering blood pressure, HF patients with low blood pressure were not included in most clinical studies as a result of sacubitril/valsartan administration, and average systolic blood pressure of most enrolled patients was around 120 mmHg. Thus, the effect of sacubitril/valsartan on cardiovascular outcomes, especially LV reverse remodeling for HF patients with LVEF < 50% and low blood pressure, remains uncertain. Purpose The aim of this study was to examine the effect of sacubitril/valsartan on LV reverse remodeling after initiation of the maximum tolerated dose of sacubitril/valsartan for HF patients with LVEF < 50% and systolic blood pressure ≤ 100 mmHg, and a comparison of its efficacy with that for patients with systolic blood pressure > 100 mmHg. Methods 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. Results sacubitril/valsartan was discontinued for 17 (10.4%) as decided by the attending physician mainly due to hypotension. The prevalence of discontinuation of sacubitril/valsartan for the low blood pressure group was higher than that for the non-low blood pressure group, but the difference was not statistically significant (16.0% vs. 9.4%, P = 0.32). No serious adverse events occurred during this study. The maximum tolerated dose of sacubitril/valsartan was lower for the low blood pressure group than for the non-low blood pressure group (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 (Figure). Conclusions Significant LV reverse remodeling can occur after initiation of sacubitril/valsartan even in HF patients with LVEF < 50% and systolic blood pressure ≤ 100 mmHg if tolerated. This finding is expected to offer new insights for better management of HF patients.Figure

Association between dapagliflozin, cardiac biomarkers, and cardiac remodeling in patients with diabetes mellitus and heart failure: a post-hoc analysis of a randomized study

Abstract Introduction Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors are a relatively new class of antidiabetic drugs, which showed favorable effects in heart failure (HF) patients, irrespective of their left ventricular ejection fraction (LVEF). Recent studies have demonstrated the beneficial effects of empagliflozin on cardiac function and structure, however, less is known about dapagliflozin. Purpose To investigate the association between the use of dapagliflozin and cardiac biomarkers as well as cardiac structure in a cohort of patients with HF and diabetes mellitus (DM). Methods The present was a post-hoc analysis of a recently published randomized study, which included 110 patients (Dapagliflozin group n = 56, Control group n = 54) with HF and DM. Inclusion criteria included: age>18 years, history of DM and HF, regardless of LVEF, and hospitalization for HF exacerbation within 6 months. Exclusion criteria were previous treatment with SGLT2i or Glucagon-like Peptide-1 Receptor agonists, a GFR< 30 and life expectancy< 1 year. The evaluation of patients (at baseline, 6 and 12 months) included clinical assessment, laboratory blood tests, and echocardiography. In order to investigate the changes in biomarkers and ultrasound indexes throughout the follow-up period in the two groups, linear mixed regression analyses were conducted. The regression equation included terms for time, group, time-group interaction, age and heart rate (HR) at baseline. Adjusted regression coefficients (β) with standard errors (SE) were computed from the results of the mixed models. Statistical significance was set at p< 0.05 and analyses were conducted using STATA statistical software (version 13.0). Results After adjusting for age and baseline HR, troponin decreased significantly throughout the follow-up period in a similar degree in both groups. Brain Natriuretic peptide (BNP) decreased significantly across all follow-up time points in both groups. However, the degree of decrease was significantly greater in the SGLT2-inhibitor group (Figure 1A, Table 1). LVEF did not change significantly over the follow-up period in the Control group, while it increased significantly in the SGLT2-inhibitor group. Left atrium (LA) increased significantly throughout the follow-up period only in the Control group, while in the SGLT2-inhibitor group there was no significant change. LA Volume index (Figure 1B), LV end diastolic volume (LVEDV), LVEDV index (Figure 1C), LV end systolic volume (LVESV), LVESV index and Global longitudinal strain (GLS) (Figure 1D) increased significantly throughout the follow-up period in the Control group, while in the SGLT2-inhibitor group they decreased significantly. LV mass index increased significantly throughout the follow-up period in a similar degree in both groups. Conclusion(s) Dapagliflozin, an SGLT2i, was associated with a reduction in cardiac biomarkers and with reverse cardiac remodeling in patients with HF and DM.Figure1.Longitudinal changesTable1.Results of the mixed LR analysis

Pulmonary venous flow changes after Mitraclip implantation is predictor of mid-term right ventricular function improvement

Abstract Background Percutaneous mitral valve repair with Mitraclip has become an effective therapeutic alternative to mitral valve surgery in high-risk surgical patients with severe mitral regurgitation. Pulmonary venous flow assessment by pulsed Doppler is widely used to determine the severity of mitral regurgitation and apparently is the best method to evaluate mitral regurgitation after the procedure because device artifacts do not affect it. The main objective of this study was to assess the impact of pulmonary venous flow changes after Mitraclip implantation in right ventricular function in the follow up at 6 months after the procedure. Methods This single-center, retrospective study included all consecutive patients with mitral regurgitation ≥ III/IV undergoing percutaneous mitral valve repair with the MitraClip device at our institution between 2010 and 2023. We analyzed the changes in the systolic/diastolic flow velocity time integral ratio in pulmonary veins pre and postprocedure. The tricuspid annular plane systolic excursion (TAPSE) was the method used to assess the right ventricular function in the follow up. Results A total of 158 consecutive patients that underwent Mitraclip implantation at our institution were included. Men age was 77 years ±10.3, and 82 patients (52.5%) were women. The etiology of mitral regurgitation was degenerative in 70 patients (44.3%), functional in 60 patients (37.9%) and mixed in 28 patients (17.7%). Preprocedurally, tridimensional effective regurgitant orifice was 0.63 ±0.33cm2, left ventricular end-diastolic volume 145.19 ± 66.14 ml (indexed 80.33 ± 59.59 ml/m2), left ventricular ejection fraction 45.90 ± 15.99%, pulmonary artery systolic pressure (PASP) 48.79 ± 18.12 mmHg and TAPSE 18.59 ± 4.43mm. The change in the pulmonary venous flow assessed by the systolic/diastolic flow velocity time integral ratio, was predictor of a right ventricular function improvement at 6 months (y = -2.7169 + 3.0171 x, r= 0.45, p= 0,006 see figure 1). Conclusions Pulmonary venous flow changes after Mitraclip implantation assessed by the systolic/diastolic flow velocity time integral ratio is predictor of mid-term right ventricular function improvement.Figure 1

The acute hemodynamic effects of sodium lactate infusion: increased cardiac output and decreased afterload in a randomized trial in pigs

Abstract Background Lactate is traditionally acknowledged as a by-product of anaerobic glucose metabolism. Recently, however, lactate has been proven to be a preferred oxidative substrate for stressed myocardium. Studies have shown that exogenous lactate infusion provides beneficial hemodynamic effects including increased cardiac output (CO). Nevertheless, the exact mechanism of action underlying the hemodynamic effects of lactate infusion has not been fully elucidated. Aim To identify the cardiovascular mechanisms behind the acute hemodynamic effects of exogenous sodium lactate infusion in an experimental model of healthy human-sized pigs. Methods We performed a randomized, assessor-blinded crossover study in eight female 60 kg pigs. In randomized order, the pigs received an infusion with 1 M sodium lactate for two hours and a control infusion with iso-osmolar and isovolumetric sodium chloride for two hours. The two infusion periods were separated by a one-hour washout period. We measured CO and pulmonary pressures hourly with a pulmonary artery catheter. A pressure-volume admittance catheter was inserted in the left ventricle to assess measures of cardiac efficiency, contractility, afterload, and preload. Hemodynamic measures as arterial blood pressure, heart rate, and mixed venous saturation (SvO2) were measured hourly as well. The study followed the principles of laboratory animal care (NIH Publication no. 85-23 revised 1985) and national and European legislations. Results Lactate levels increased by 9.9 mmol/L (95% CI 9.1 to 11.0) and CO increased by 2.0 L/min (95% CI 1.2 to 2.8) during lactate infusion as compared with the control period (figure 1). During lactate infusion, ejection fraction increased by 16.0 percentage points (95% CI 1.9 to 31.0) and heart rate by 21 bpm (95% CI 9 to 32) compared with control. Arterial elastance decreased by -1.1 mmHg/ml (95% CI -2.1 to -0.18). Lactate infusion also increased cardiac efficiency, SvO2, arterial pH, and arterial glucose concentration significantly. The infusion of lactate led to no changes in systemic arterial pressure nor pulmonary pressures including pulmonary artery wedge pressure. Also, no changes were found in left ventricle end systolic elastance (contractility). Futhermore, no change in left ventricle end-diastolic volume or -pressure (preload) were observed during lactate infusion compared with the control (figure 2). Conclusion High dose lactate infusion increased cardiac output by reducing afterload. No changes in left ventricular contractility or -preload were observed.Fig 1:Lactate concentration and COFig 2:Changes of endpoint parameters

Improvement in myocardial energetics and perfusion with Liraglutide in patients with type 2 diabetes- A randomised, single centre, open label, cross-over drug trial

Abstract Background Both the insulin secretion and insulin resistance in Type 2 diabetes (T2D) are amenable to pharmacological intervention. In a single center, open-label, randomized, cross-over design trial we sought to compare two distinct glycaemic control strategies of targeting beta-cell dysfunction and promoting insulin secretion using Glucagon-like peptide-1 receptor agonists (GLP-1RA) -liraglutide and targeting peripheral insulin resistance using a peroxisome proliferator activated receptor-gamma agonist (PPAR-g)-pioglitazone to see which results in greater improvements in myocardial perfusion, energetics and function in patients with T2D. Methods Fifty-two T2D patients were screened. Eligible patients with no known prior cardiovascular disease were randomized in a 1:1 ratio to be administered one of the study drugs for a 16-week treatment period followed by an 8-week washout and a further 16-week treatment period for the second drug. Thirty-three eligible participants completed both treatment periods. Participants have undergone 31phosphorus magnetic resonance spectroscopy (31P-MRS) at rest and dobutamine stress followed by the cardiac magnetic resonance (CMR) scans. The CMR protocol consisted of rest and dobutamine stress cine imaging, perfusion imaging (motion corrected, automated in-line perfusion mapping), velocity-encoded mitral in-flow imaging and late gadolinium enhanced imaging at 3T immediately before commencement and after completion of each treatment arm (four scans per participant). Results Clinical and biochemical characteristics, and CMR/31P-MRS results are provided in Tables 1&2 respectively. Liraglutide therapy resulted in a significant reductions in the body mass index and significant improvements in glycemic control. Both drugs reduced insulin resistance indicated by a reduction in the mean triglyceride index. There were no significant changes in NTproBNP or troponin levels with either drug. Therapy with either drug did not result in a significant change in the LV end-diastolic volume, ejection fraction or global longitudinal shortening. Pioglitazone led to a significant increment in mean LV mass and LV mass index, while no significant effect in myocardial mass or mass index were detected with liraglutide. Liraglutide therapy resulted in increased rest and dobutamine stress energetics, global stress myocardial blood flow and myocardial perfusion reserve index. While pioglitazone treatment showed no significant effect in these parameters, an isolated improvement in the rest diastolic function was detected in this arm. Conclusions In this randomised cross-over design trial we showed for the first time that four months treatment with glucagon like protein 1 receptor agonist liraglutide results in significant improvements in myocardial stress perfusion and energetics. Pioglitazone results in an isolated improvement in rest diastolic funct

Prevalence of pulmonary hypertension in reduced left ventricular systolic function and its influence on outcomes

Abstract Background/Introduction Reduced left ventricular (LV) systolic function can lead to pulmonary hypertension (PHT). However, the significance of PHT complicating reduced LV systolic function remains poorly characterised. Purpose We aimed to describe the prevalence and prognostic importance of PHT in a large cohort of adults with at reduced left ventricular ejection fraction (LVEF). Methods We analysed the National Echocardiography Database of Australia (data from 2000-2019). Adults with a recorded tricuspid regurgitation (TR) peak velocity and LVEF <50% were included. Patients with moderate or greater left sided valvular pathology were excluded, as were patients with prior aortic or mitral valve replacements. These subjects (n= 23675) were then categorised according to their TR peak velocity. The relationship between PHT severity and mortality outcomes were evaluated (median follow-up of 2.9 years, interquartile range 1.0-5.4years). Results Subjects were aged 70±15years and 31.7% were female. Overall, 8801 (37.2%), 7061 (29.8%), 5676 (24.0%), and 2137 (9.0%) patients had normal (TR peak velocity <2.5m/sec), borderline (2.5-2.8m/sec), intermediate (2.9-3.4m/sec), or high risk PHT (>3.4m/sec), respectively. An echocardiographic phenotype for ‘left heart disease’ was evident with worsening PHT, showing rising E:e’ ratio and a greater proportion of right ventricular (RV) dilation and dysfunction (p<0.0001 for all). Left and right atrial sizes increased from low-intermediate risk, before plateauing at high risk PHT (p<0.0001). With increasing risk of PHT, 1- and 5-year actuarial mortality increased from 13.3% and 43.8%, to 41.5% and 81.4% respectively (p<0.0001). After adjustment for age, sex, LVEF, LV end diastolic diameter and LA volume index, the risk of mortality increased as TR peak velocity increased (adjusted hazard ratio (aHR) 1.31, 95% confidence interval 1.23-1.38 in borderline risk, to aHR2.38, 95%CI 2.21-2.56 in high risk PHT) (Figure 1). The cohort was also assessed in two groups based on LVEF severity according to guidelines. The sub-group of patients with mildly reduced LVEF (40-49%, n = 12495) showed that mortality risk increased as risk of PHT increased; (aHR 1.38, 95%CI 1.27-1.50 in borderline risk, to aHR2.82, 95%CI 2.52-3.15 in high risk PHT). Similarly, those with reduced LVEF (<40%, n = 11180) mirrored these trends (aHR 1.23, 95%CI 1.14-1.33 in borderline risk, to aHR2.07, 95%CI 1.88-2.28 in high risk PHT). There was a mortality threshold seen from TR peak velocity 2.41m/sec onwards (aHR1.18, 95%CI 1.04-1.33) (Figure 2). Conclusion(s) In this large cohort study, we demonstrate that PHT risk is common in patients with reduced LV systolic function and mortality increases as PHT becomes more severe. A threshold for higher mortality lies within the range of "borderline-intermediate" risk PHT.Adjusted Risk for All-Cause MortalityThreshold for Mortality

Effect of Sacubitril/Valsartan and enalapril on left ventricular function in patients with hematologic malignancies after bone marrow transplantation

Abstract Background and Aims Optimizing treatment for heart failure early after initiation of chemotherapy may prevent myocardial dysfunction. We hypothesized that early initiation of treatment with sacubitril/valsartan (sac/val) or enalapril (ena) may prevent cardiotoxicity. Patients and methods 90 patients (mean age 45.7 ± 14,1 years old, 52 male) with normal LV ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation, were randomized to receive sacubitril/valsartan 24/26 mg bid daily or enalapril 5 mg bid daily or placebo. We measured at baseline, before transplantation and after six months: i) Global Longitudinal Strain (GLS) of left ventricle (LV) by speckle tracking imaging, ii) myocardial global work index (GWI), global constructive work (GCW), global wasted work (GWW) and myocardial global work efficiency (GWE), by longitudinal strain-peripheral blood pressure loops, and iii) Left Ventricular Ejection Fraction (LVEF). Results The 3 treatment groups had similar age, sex, risk factors and cardiotoxic medication before and after bone marrow transplantation. Compared to baseline, patients treated with sacubitril/valsartan or enalapril for six months did not show a deterioration of LV GLS (-19.8±2.8 vs -19.3±4.1%, p=0.403 for sac/val, -20.3±2.8 vs -20.0±3.6%, p=0.634 for ena). Conversely, patients treated with placebo for six months, presented a significant impairment of LV GLS (-20.9±2.1% vs -18.5±2.2, p=0,001). No significant changes were found in LVEF after treatment with sacubitril/valsartan or enalapril for six months (57.5±4.9 vs 57.9±6.8%, p=0.826 for sac/val, 58.8±5.4 vs 60.7±7.1%, p=0.419, for ena), while a borderline deterioration was noticed after treatment with placebo (60.6±5.4 vs 57.7±6.7%, p=0.045). Moreover, in the sacubitril/valsartan group, we noticed a significant reduction of left ventricular end diastolic and end-systolic volume [(102.3±26.9 vs 93.9±21.5 ml, p=0.042 and 44.5±15.4 vs 38.6±9.6ml, p=0.012), respectively]. At 6 months, we did not observe any alteration in GWi, GCW, GWW, GWE in patients treated with enalapril (p>0.05). Conversely, in patients treated with sacubitril/valsartan GWE was improved (94.2±3.1 vs 95.8±1.8 %, p=0.030) and GWW was reduced (111.5±75.7 vs 86.4±43.1 mmHg%, p=0.045), while GWI and GCW did not show any significant alteration. Conversely, in the placebo group, GWI was reduced (1909.9±336.4 vs 1727.9±340.9 mmHg%, p=0.027), GWW was increased (80.7±60.6 vs 110.6±65.1 mmHg%, p=0.045), GWE was also reduced (94.2±3.1 vs 95.8±1.8 %, p=0.030) and GCW did not change at 6 months. Conclusions Treatment with sacubitril/valsartan or enalapril prevented deterioration of myocardial function six months after bone marrow transplantation in patients with hematologic malignancies and preserved LV ejection fraction. Moreover, sacubitril/valsartan showed a more favorable effect on myocardial work.

Effects of pirfenidone on scar size and ventricular remodeling after myocardial infarction: a preclinical study

Abstract Background An intense fibrotic response after myocardial infarction (MI) may lead to scar expansion and left ventricular (LV) remodeling, increasing the risk for ventricular arrhythmias and heart failure. Pirfenidone is a drug currently approved for the treatment of idiopathic pulmonary fibrosis, and reduces LV fibrosis in patients with heart failure and preserved ejection fraction. We aimed to characterize the different profiles or protein expression in the infarct zone in rats receiving or not receiving pirfenidone on top of standard therapy for MI. Methods Male Wistar rats were randomized to: sham procedure (group 1; n=13), reperfused MI induced by surgical ligation of the left anterior descending artery (LAD) for 45 minutes (group 2; n=17), reperfused MI plus standard therapy (aspirin, angiotensin-converting enzyme inhibitor, beta-blocker, and also mineralocorticoid receptor antagonist [MRA]) (group 3; n=17), reperfused MI plus pirfenidone alone (group 4; n=17), reperfused MI plus standard therapy and pirfenidone (group 5; n=17). Rats surviving LAD ligation and reperfusion underwent cardiac magnetic resonance (CMR) after 72 hours and 30 days from MI, and were sacrificed the day after the second CMR exam. The primary endpoint was the change in late gadolinium enhancement (LGE) mass as a percentage of LV mass. Results Forty-six rats survived until the second CMR. Percent changes in LV end-diastolic and end-systolic volume (p=0.370 and 0.423, respectively), ejection fraction (p=0.236) and mass (p=0.815) did not differ significantly between rats on pirfenidone plus standard therapy compared with those receiving standard therapy alone. The decrease in LGE mass was significantly greater in rats on pirfenidone plus standard therapy vs. those on standard therapy alone: -22.0% (interquartile range, -37.1 to -5.7, range -51.1 to +37.5) vs. +1.9% (-7.7 to +12.5, range -19.8 to +56.5), p=0.029. Conclusions Pirfenidone had additive effects to standard therapy for MI (including an MRA) in reducing LV fibrosis in a rat model of reperfused MI, while it did not further improve LV function, volumes or mass.

Treatment with sacubitril/valsartan and improvement of ventricular-arterial coupling in heart failure with reduced ejection fraction

Abstract Background Treatment with the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan (S/V) in patients with heart failure and reduced ejection fraction (HFrEF) reduces mortality and heart failure (HF) hospitalizations. The specific hemodynamic mechanisms underlying these beneficial effects are currently unclear. Purpose This study aimed to assess the effects of S/V treatment on left ventricular (LV) end-systolic elastance (Ees), effective arterial elastance (Ea), and the ventricular-arterial coupling ratio (Ea/Ees) in patients with HFrEF using non-invasive pressure-volume analysis. Methods 117 patients with symptomatic HF and LVEF <40% in whom treatment with S/V was initiated were enrolled in this multicenter German prospective study. We used transthoracic echocardiography with simultaneous arm-cuff blood pressure measurements for non-invasive pressure-volume loop analyses. Primary endpoints were changes in Ees, Ea, and Ea/Ees ratio after six months of S/V treatment. Results The mean age was 65 (±13) years and 30% were female. In 54.7% of the patients, the etiology of HF was ischemic, and 45.3% was non-ischemic. 58.4% had first HF diagnosis at baseline. 102 patients with complete clinical and echocardiographic data at baseline and after six months of follow-up were analyzed. Among those, 62% were on target dose of S/V. Six months of S/V treatment resulted in a significant increase of Ees (0.66 mmHg/ml, IQR [0.45;0.94] vs. 0.78 mmHg/ml [0.57;1.10], p=0.001) and decrease of Ea (1.76 mmHg/ml [1.48;2.13] vs. 1.62 mmHg/ml [1.36;1.96], p=0.014). Hence, the Ea/Ees ratio significantly improved (2.52 [1.88;4.05] vs. 1.93 [1.50;2.63], p<0.001). In addition, LV volumes and pressure improved significantly with a regression of the LV end-systolic volume (LVESV: 142 ml [115;180] vs. 96 ml [65;124]), end-diastolic volume (LVEDV: 216 ml [179;247] vs. 165 ml [132;200]) and LV end-diastolic pressure (LVEDP: 19.6 mmHg [18.2;22.4] vs. 17.8 mmHg [16.6;19.9]), p<0.001 respectively. The LVEF increased from a median of 33% (27;37) to 43% (36;49), p<0.001. NT-proBNP level decreased from (median) 1771 pg/ml [838;5211] to 724 pg/ml [300;1575] and mean 6-minute walking distance increased from 371m (±125) to 423 m (±122), p<0.001 respectively. The percentage of patients with NYHA class III changed from 25.6% to 5.9%. Conclusion In a 6-months treatment period, initiation of sacubitril/valsartan in patients with heart failure and reduced ejection fraction was associated with reduction of LV volumes, improved LV function, reduction in afterload and fewer heart failure symptoms. These new data indicate that beyond reverse LV remodeling, improvement of LV contractility and ventricular-arterial coupling may contribute to the favorable clinical outcomes on treatment with sacubitril/valsartan in chronic heart failure.

Impact of sacubitril valsartan initiation in patients with HFrEF and severe mitral regurgitation referred for percutaneous mitral repair

Abstract Background In patients with heart failure with reduced ejection fraction (HFrEF), the severity of functional mitral regurgitation (MR) is a major predictor of worsened symptoms and poor outcomes. Percutaneous MR repair has been shown to improve outcomes in HFrEF with MR. However, because MR is related to abnormal myocardial function and adverse remodeling, the optimization of guideline-directed medical therapy (GDMT) could improve loading conditions, reversal remodelling and left ventricle function and also may reduce MR severity. We sought to evaluated whether the left ventricle reverse remodeling induced by the addition of sacubitril/valsartan may reduce MR severity sufficiently to avoid need for percutaneous MR repair approach. Methods We performed a single-center, prospective assessor-blinded study to determine the reverse remodeling response of sacubitril/valsartan therapy in HFrEF patients (NYHA class II-IV) with MR evaluated for percutaneous MR repair. Echocardiographic images were assessed offline by 2 investigators blinded to both the clinical data and timing of echocardiograms. Doses of sacubitril/valsartan were optimized to individual tolerance. A clinical and echocardiographic 1 year follow-up was performed. Results Thirty-nine HFrEF patients with MR grade 3-4 were included (mean age 63 years old, 69,2% male). Optimal dose of sacubitril/valsartan was reached in 63,2% of patients. After 1-year follow-up, only 1 patient died and, as we show in Table 1, a significant improvement on NYHA functional class and NT-ProBNP values were present. Left ventricle ejection fraction improved (29.7 ± 6.7% vs 41.3 ± 13.2%; P < 0.001) and left ventricular end-diastolic and end-systolic volume indexed to body surface area decreased (123.4 ± 35.7 mL/m2 vs 98.4 ± 39.7 mL/m2; P < 0.001 and 87.7 ± 30.0 mL/m2 vs 61.9 ± 35.3 mL/m2; P < 0.001, respectively). Volumetric remodeling was associated with a reduction in the degree of mitral regurgitation (64.1% grade 3 and 35.9% grade 4 at the beginning to 28.9% grade 1, 36.8% grade 2, 21.5% grade 3 and 13.2% grade 4 after one year of follow-up; [scale from 0-4]). Conclusion The optimization of GDMT with sacubitril/valsartan induced an improvement on functional class and a beneficial reverse cardiac remodelling, with enhancement of left ventricle function and reducing MR severity, enough in 24 patients to avoid need for percutaneous MR repair. In HFrEF patients with grade 3-4 mitral regurgitation, our results reinforce importance of ensuring optimal GDMT before a percutaneous mitral valve repair approach.Table 1.Changes during follow-up.

The paradox of the association between epicardial adipose tissue, infarct size and left ventricular remodelling after ST-segment elevation myocardial infarction: a CMR study

Abstract Background Epicardial adipose tissue (EAT) is a biologically active fat deposit contained below the visceral pericardium. In latest years, EAT has emerged as a predictor of atherosclerosis, coronary artery disease and adverse cardiovascular events. Nevertheless, EAT significance after ST-segment elevation myocardial infarction (STEMI) in acute phase and its association with left ventricular remodelling is unknown. Purpose We aimed to assess the association of cardiac magnetic resonance (CMR)-derived EAT with the extent of infarct size (IS), microvascular obstruction (MVO) and left ventricular remodelling in a homogeneous cohort of STEMI patients. Methods We prospectively included 255 patients discharged after a first reperfused, anterior STEMI. An early CMR (1-week after STEMI) was performed in all patients. EAT volume (mL/m2), left ventricular (LV) end-diastolic and end-systolic indexed volumes (LVEDiV and LVESiV, mL/m2), left ventricular ejection fraction (LVEF, %), infarct size (IS, % of LV mass) and microvascular obstruction (MVO, % of LV mass) were quantified. A subgroup of 195 patients underwent a follow-up (6-month) CMR. Patients were categorized as extensive EAT (>35 mL/m2) or non-extensive EAT (≤35 mL/m2) according to the upper tertile of this parameter. A specific analysis was performed in patients with extensive IS (>30% of LV mass). Results Patients with extensive EAT were older (62±12 vs. 57±13 years, p=0.004), had an increased prevalence of diabetes mellitus (31% vs. 16%, p=0.007) and depicted a worse baseline risk profile (GRACE risk score 138±37 vs. 126±36 points, p=0.02). At 1-week CMR, patients with extensive EAT displayed larger IS (31±17% vs 24±16%, p=0.001), more MVO (1.4 [0-6.2]% vs 0 [0-2.5]% of LV mass, p=0.022) and more myocardial oedema (39±16% vs 32±17% of LV mass, p=0.003). After adjustment for baseline characteristics, EAT was independently associated with IS (standardized beta coefficient=0.30, p<0.001). However, patients with extensive EAT did not show neither larger LV volumes nor more depressed LVEF (p>0.1 for all comparisons). In the extensive IS subgroup (n=69, 27%), patients with extensive EAT depicted less dilated ventricular volumes (LVEDiV 90±26 vs 111±40 mL/m2, p=0.011; LVESiV 51±26 vs 72±36 mL/m2, p=0.009) and higher LVEF (46±13 vs. 38±10%, p=0.007) at 6-month CMR. At 6-month CMR, in a propensity score-matched population (n=170, 85 with extensive EAT and 85 without extensive EAT), EAT was independently associated with more preserved LVEF, and less dilated LVEDiV and LVESiV only in the subgroup of patients with extensive IS (p<0.05 for all comparisons) (Figure 1). Conclusions EAT seems to exert a bimodal effect in patients with anterior STEMI. More extensive EAT is associated with more extensive infarct size in acute phase but, in patients with large IS, those with extensive EAT display less adverse remodelling during follow-up. This "paradox" of EAT after STEMI merits further investigation.Figure 1.

Echocardiographic characterization of patients with supranormal ejection fraction: pooled core laboratory analysis of the TOPCAT and PARAGON-HF trials

Abstract Background Patients with heart failure and supranormal ejection fraction (HFsnEF) may be phenotypically distinct from those with normal or below normal left ventricular ejection fraction (LVEF), and may demonstrate different prognostic trajectories or treatment responses. Purpose To characterize clinical features, cardiac structure and function among patients with HF with preserved EF (defined as 45% ≤ LVEF ≤ 65%) and supranormal EF (defined as LVEF>65%). Methods Baseline clinical characteristics and key echocardiographic parameters from patients enrolled in the echocardiographic substudies of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist)-Americas and PARAGON-HF (Prospective Comparison of ARNI [angiotensin receptor–neprilysin inhibitor] with ARB [angiotensin-receptor blocker] Global Outcomes in Heart Failure with Preserved Ejection Fraction) were compared between patients with and without HFsnEF. Results Among 1,751 participants (mean age 73 years old, 51% women) in this pooled core laboratory analysis, 265 (15%) had HFsnEF. Participants in HFsnEF group were more likely to be women, and less likely to have prior myocardial infarction and atrial fibrillation (Table 1). Compared with those with LVEF ≤ 65%, those with LVEF > 65% had lower LV end-diastolic and end-systolic volume indices, lower LV mass index, higher LV relative wall thickness, and higher right ventricular fractional area change. LV geometry and measures of LV diastolic function were similar in both groups (Table 1). Global longitudinal strain (GLS) was abnormal (absolute GLS <16%) in 28% in those with HFsnEF compared with 53% in those with LVEF ≤ 65%. After adjusting for baseline LV ejection fraction and sex, and stratified by trial, abnormal GLS was associated with a higher risk of composite of first heart failure hospitalization or cardiovascular death (overall hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.23 – 1.98, P < 0.001), cardiovascular death (overall HR 2.06, 95% CI 1.35 – 3.13, P = 0.001), and heart failure hospitalization (overall HR 1.49, 95% CI 1.15 – 1.93, P = 0.003) in both HFsnEF and non-HFsnEF groups (P-interaction > 0.05 for all, Figure 1). Conclusions Among participants in the TOPCAT-Americas and PARAGON-HF trials, those with LVEF > 65% were predominantly women, had less LV remodeling, and had better RV function based on echocardiographic measures. Nevertheless, despite supranormal LVEF, GLS was abnormal in over a quarter of patients and remained an important predictor of adverse clinical outcomes in this cohort.Table 1Figure 1

Sport-specific cardiac adaptation in 104 female elite athletes: MRI findings from the ELITE cohort

Abstract Background The overlap between exercise-induced cardiac remodelling (EICR) and cardiac pathology is a key challenge in sports cardiology. Mainly based on findings in male athletes, EICR is thought to be sport-specific, and varyingly characterised by increased ventricular volumes, cardiac mass and/or wall thickness. However, no large cardiac magnetic resonance imaging (CMR) study in female elite athletes has extensively examined sport-specific cardiac adaptations. Purpose To investigate sport-specific EICR on CMR in a large cohort of female elite athletes. Methods We performed a cross-sectional CMR analysis in female elite athletes (Para-/Olympic or professional athletes competing ≥10 hours per week at a national/international level) aged ≥16 years, included in the ELITE cohort (1). We excluded athletes with known cardiovascular disease, and classified athletes according to the ESC sports disciplines classification. Our outcomes of interest were sport-specific EICR, defined as BSA-indexed LV and RV end-diastolic volume (EDVi), LV wall mass (LVMi), and maximal LV wall thickness (LVWdmax), LV remodelling index (LVMi/LVEDVi), and LV/RV ratio (LVEDi/RVEDVi). CMR was performed according to a uniform protocol, preferentially on 1.5T. A dedicated core-lab analysed all CMRs in Circle Cardiovascular Imaging. Results We included 104 female elite athletes, 96% Caucasian, mean age of 26.1 ±5 years, BSA 1.8 ±0.1 m2, and mean professional (≥10 hours/week) athlete years of 11.6 ±5. The athletes were classified as skill (n=8), power (n=9), mixed (n=39) and endurance (n=48) sports. Endurance athletes had markedly increased left- and right ventricular volumes compared to power (LVEDVi 111.2 ±15 vs 98.7 ±11 ml/m2, p=0.009; RVEDVi 114.8 ±18 vs 101.7 ±10 ml/m2, p=0.006) and mixed athletes (LVEDVi 111.2 ±15 vs 107.3 ±13 ml/m2, p=0.058; RVEDVi 114.8 ±18 vs 107.8 ±12 ml/m2, p=0.031) (Figure 1). No differences were found between endurance, mixed, power and skill athletes in LVEDVi/RVEDVi ratios (0.97 vs 0.99 vs 0.97 vs 0.99), LVMi (52.6 ±12 vs 46.9 ±10 vs 48.7 ±10 vs 50.4 ±11 g/m2) (Figure 2), LVWdmax (8.1 ±1 vs 7.9 ±1 vs 7.9 ±1 vs 8.9 ±1 mm), LV remodelling index (LVMi/LVEDVi 0.47 vs 0.44 vs 0.49 vs 0.48), LV ejection fraction (56.3 ±4 vs 56.7 ±5 vs 58.2 ±3 vs 57.7 ±3 %), and RV ejection fraction (54.6 ±4 vs 55.7 ±4 vs 55.4 ±3 vs 56.7 ±4). Conclusion In female elite athletes, EICR according to sport categories is mainly characterised by balanced increases in ventricular volumes in endurance athletes, but not in increases in left ventricular wall-mass and thickness, even in sport categories with high static demands. Our findings constitute a first step towards the understanding of sport-specific EICR in female elite athletes.Figure 1.Figure 2.

Long-acting CRF2 peptide agonist improves cardiac function in a rat heart failure model

Abstract Introduction Corticotropin-releasing factor receptor type 2 (CRF2) is a G protein-coupled receptor largely expressed in the cardiorenal system. Upon CRF2 activation, endogenous ligands such as urocortin-2 (UCN-2) or urocortin-3 (UCN-3) have been reported to increase cardiac function, decrease vascular resistance and improve natriuresis and diuresis in heart failure (HF) patients and in various experimental heart failure settings. However UCN-2 or -3 suffer from a very short half-life which markedly limit further clinical investigations in HF patients. For this purpose, a very long acting CRF2 peptide agonist has been developed. Objectives The aim of this study is to determine the acute effect on cardiac hemodynamic of a long acting CRF2 peptide agonist, COR-1167, in a rat model of chronic heart failure. Methods In 10-week-old Wistar rats, a total occlusion of the left anterior descending coronary artery was performed to induce myocardial infarction. Twelve weeks after myocardial infarction, rats had developed heart failure and received COR-1167 at the dose of 0.3 µg/kg or 1 µg/kg, or placebo, administered SC. Left ventricular dimensions and function were then assessed by echocardiography and left ventricular pressure-volume analysis. Results Three months after left coronary artery ligation rats displayed the classical features of heart failure as illustrated by an increase in left ventricular diastolic diameter and reduced ejection fraction, and decreases in LV end-systolic pressure, dP/dtmax and LV end-systolic pressure volume relationship. Major LV diastolic dysfunction developed, as shown by the increases in LV end-diastolic pressure, and LV end-diastolic pressure volume relationship and the decrease in dP/dtmin. Echocardiography and left ventricular pressure-volume analysis showed that COR-1167 at 0.3 and 1 µg/kg SC improved in a dose-dependent manner cardiac contractility and relaxation as assessed by LVESPVR and LVEDPVR, respectively. In addition, stroke volume and cardiac output were significantly ameliorated by COR-1167 at 1.0 µg/kg SC, with no change in heart rate. Conclusion Single acute administration of COR-1167 improved cardiac function in a rat model of heart failure with reduced ejection fraction. Altogether these results confirm that CRF2 agonism is an attractive therapeutic target for the treatment of heart failure.

Shared and distinguishing phenotypic characteristics of filamin c and desmoplakin cardiomyopathy

Abstract Background Rare truncating variants in the genes Filamin C (FLNC) and Desmoplakin (DSP) are increasingly recognised causes of Dilated Cardiomyopathy and Arrhythmogenic Cardiomyopathy (1,2). A direct comparison of both genotypes is needed to aid in subclassification and genotype-specific risk modelling. Purpose We sought to identify shared and distinguishing clinical characteristics and imaging phenotypes between FLNC and DSP cardiomyopathy. Methods 41 patients with ‘pathogenic’ or ‘likely pathogenic’ FLNC or DSP variants by American College of Medical Genetics (ACMG) criteria were identified from a tertiary centre cardiovascular genetics laboratory. Clinical, genetic and imaging data were compiled. Continuous variables are presented as median [IQR] or mean±SD and analysed by nonparametric Mann Whitney U or t-test. Categorical variables were analysed by Chi-Squared or Fisher’s exact test. Results FLNC and DSP cohorts included a similar proportion of patients with truncating variants (91% vs 100%) and female sex (12/21, 57% vs 13/20, 65%). FLNC patients were younger (median age 30 [13-51] vs 57 [41-65] years, p<0.0008) and more likely to present with sustained ventricular arrhythmia (5/21 24% vs 3/20, 15%) (Table 1). Acute myocarditis episodes were exclusively linked to DSP cardiomyopathy (4/20, 20%) with no association to FLNC (0/21, 0%, p<0.05). FLNC cardiomyopathy patients had normal left ventricular (LV) systolic function (LVEF 57±9% SD vs 46±13% DSP, p<0.03) and normal left ventricular cavity side (mean indexed LV end diastolic volume (EDV) 85±12 vs 112±26ml/m2 DSP, p<0.02) (Table 2). Both FLNC and DSP cause exclusive left ventricular or biventricular late gadolinium enhancement (75% Vs 82%) on cardiac magnetic resonance imaging (MRI). Fibrosis was predominantly in a subepicardial distribution in both cohorts (66% FLNC vs 57% DSP). In FLNC, circumferential fibrosis was the most frequent pattern of distribution (5/9, 55%), whereas in DSP inferior and lateral wall fibrosis was the predominant feature (8/14, 57%). There were no cases of isolated RV involvement and no cases fulfilled ‘definite’ ARVC taskforce diagnostic criteria. Over a follow up of median 45months, there was no significant difference in the proportion of FLNC and DSP patients experiencing a composite end point of LVAD implantation, heart transplant, aborted sudden cardiac death or mortality (7/21, 33% FLNC Vs 7/20, 29% DSP p>0.99). Conclusion Normal systolic function with marked circumferential fibrosis is the predominant feature of FLNC cardiomyopathy whereas mild LV dilatation, mild systolic impairment and inferolateral fibrosis are more frequent in DSP cardiomyopathy. Myocarditis episodes are a distinguishing feature of DSP cardiomyopathy, suggesting a different underlying molecular mechanism driven by inflammation. The overall clinical trajectory of FLNC and DSP cardiomyopathy patients are comparable.

Outcome of transcatheter mitral valve repair in heart failure patients with reduced ejection fraction and severe left ventricular dilatation

Abstract Introduction The COAPT trial demonstrated the benefit of transcatheter edge­to­edge mitral valve repair (TEER) for heart failure patients who had reduced ejection fraction (HFrEF) with symptomatic secondary mitral regurgitation (MR). However, patients with severe left ventricular (LV) dilatation were not included in the COAPT trial. Furthermore, disproportionate LV dilatation was suggested as a possible explanation for the lack of benefit in the MITRA­FR trial. Purpose The purpose of this study was to assess the safety and efficacy of TEER in HFrEF patients with severe LV dilatation. Methods We studied 75 HFrEF patients who underwent mitral valve repair between 2018-2021. Reduced LV ejection fraction (LVEF) was defined as LVEF of 40% or less. These patients were categorized with and without severe LV dilatation based on left ventricular end-diastolic volume index (LVEDVI) using a median cut­off value of >139ml/m2 in men and >128cm/m2 in women. Results There were 37 patients with severe LV dilatation (D) and 38 without (ND). Median LVEDVI was 172 [149-190] ml/m2 in the D group vs 120 [105-127] ml/m2 in the ND group. Compared to the ND patients, patients with severe LV dilatation were more treated with SGLT2-inhibitor (rate 24% vs 3%), had lower LVEF (30 [25-31] % vs 32 [30-36] %), and higher BNP (1160 [683-2586] vs 619 [396-1253] pg/ml). There was no significant difference in MR grade (4 [3-4] vs 4 [3-4]), EROA (0.32 [0.22-0.66] vs 0.34 [0.24-0.48] cm2), NYHA class (3 [2-4] vs 3 [2-3]) and mean systolic pulmonary pressure (31 [20-43] vs 34 [25-41] mmHg). Peri­procedural adverse events were rare in both groups. 1 patient had pseudoaneurysm in the ND group, and 1 patient had cardiogenic shock and 1 patient had stroke after the procedure in the D group. At discharge, there was marked improvement in MR grade (1 [1-2] vs 1 [1-2] for both). D group had a tendency of higher reduction in LVEDVI (-12 [-24--1] vs -5[-13-4] ml/m2) than ND group. BNP level of the D group had a significantly higher degree of decline before discharge (-458 [-141--1566] to -102 [+51--306] pg/ml) than that of ND group. No differences were noted in mortality between two groups (Figure). Conclusion TEER in HFrEF patients with severe LV dilatation seems to provide similar outcomes compared to patients with less severe dilatation. Further studies are needed to clarify the indication and establish the effectiveness of TEER in these patients.

A systematic review and meta-analysis of cardiac resynchronization therapy in inotrope-dependent heart failure: an update

Abstract Background Inotrope-dependent heart failure (HF) carries a poor prognosis. Advanced mechanical supports have been viewed as primary treatment modalities for these patients, but cardiac resynchronization therapy (CRT) is an emerging alternative. Whether CRT is viable in HF patients who require inotropic support is uncertain. Purpose To assess outcomes of CRT in end-stage inotrope-dependent HF. Methods Following PRISMA guidelines, we searched Medline, EMBASE, Scopus, and Cochrane Library until December 31st 2022, with the following terms: "end-stage heart failure," "catecholamine-dependent overt heart failure," "inotrope-dependent heart failure," "advanced heart failure," "New York Heart Association class IV," "NYHA class IV." These terms were combined with "cardiac resynchronization therapy" OR "CRT" OR "biventricular device". Studies were included if: 1) HF patients required on inotropic support at CRT implantation; 2) patients were at least 18 years old; and 3) provided a clear definition of "inotrope dependence" or "inability to wean." A meta-analysis with random effects was performed in R (Version 3.5.1) with data presented as mean ± standard error. Results 19 studies comprised of 386 inotrope-dependent HF patients (mean age 64.4 ± 1.2 years, 76.9% male, 54.6% non-ischemic cardiomyopathy, mean QRS duration 168.0 ± 4.6 ms, mean follow-up 778 ± 110.7 days) were included for meta-analysis. A large majority of patients survived until discharge at 90% (95% CI: 81.0%-96.8%, I2=51%, p=0.04, Figure 1A), 88.6% were weaned off inotropes (95% CI: 77.5%-96.8%, I2=64%, p<0.01), and mean time to discharge post-CRT was 7.8 days (95% CI: 3.9-11.7, I2= 84%, p<0.01). After one year of follow-up 69.5% survived (95% CI: 59.2%-78.9%, I2=53%, p=0.02, Figure 1B) and 59.1% (95% CI: 50.1%-67.8%, I2=58%, p<0.01, Figure 1C) were alive at the end of follow-up. During follow-up the mean number of hospital admission for HF was reduced by 1.87 (95% CI: 2.70-1.04, I2=77%, p=0.04). Post-CRT mean QRS duration was reduced by 29.0 ms (95% CI: 41.33-16.68, I2=69%, p=0.006, Fig) and mean left ventricular ejection fraction increased by 4.83% (95% CI: 3.09%-6.57%, I2=16%, p=0.31, Fig). The mean NYHA class post-CRT was 2.7 (95% CI: 2.5-3.0, I2=56%, p=0.03, Figure 2A), 39.6% (95% CI: 18,.7%-62.3%, I2=83%, p<0.01, Figure 2C) improved to NYHA class III and 34.6% (95% CI: 16.4%-55.2%, I2=79%, p<0.01, Figure 2D) improved to NYHA class II. Responders to CRT tended be male (85.7% vs. 40%, p=0.015), have a history of left bundle branch block (71.4% vs. 30%, p=0.036) or an increased left ventricular end-diastolic volume (274.3 mL vs. 225.9 mL, p=0.038). Conclusion(s) Our results suggest that CRT is an alternative option for end-stage inotrope-dependent HF, improving survival, NYHA status, and HF readmission. CRT responders appear to be male with evidence of preserved diastolic function or a history of a left bundle branch block.

Cardiac magnetic resonance for prophylactic implantable-cardioVerter defibrillator therapy international registry in patients with ischemic cardiomyopathy

Abstract Background Sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) remains a leading cause of death. Current guidelines provide a class I recommendation for implantable cardioverter–defibrillator (ICD) implantation in ICM patients with transthoracic echocardiographic (TTE) left ventricular ejection fraction (LVEF) ≤35%. and NYHA functional class II or III. The current paradigm is suboptimal in identifying patients who are likely to benefit. In fact, only a relatively small proportion of ICD recipients for SCD primary prevention receive appropriate device therapy and instead there is a not negligible percentage of patients who experienced SCD event despite not fulfilling criteria for implantation. Purpose The DERIVATE-ICM registry sought to evaluate the additional prognostic value for the indication of ICD implantation using cardiac magnetic resonance (CMR) as compared to standard of care based on TTE in a large cohort of ICM patients. Methods We enrolled 861 ICM patients (86% male, mean age 65±11 years) with chronic heart failure and TTE-LVEF<50%. Major adverse arrhythmic cardiac events (MAACE), defined as the combination of SCD, aborted SCD event, and sustained ventricular tachycardia. were the primary endpoint. Independent predictors were used to calculate a CMR risk score for each patient. Risk levels were defined as low (quantile 1 [Q1]), medium (Q2 and Q3) and high (Q4). Results During a median follow-up of 1054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR:1.007, 95%CI:1.000-1.011, p=0.05), CMR-LVEF (HR:0.972, 95%CI: 0.945-0.999, p=0.045) and late gadolinium enhancement (LGE) mass (HR:1.010, 95%CI: 1.002–1.018, p=0.015) were independent predictors of MAACE. Based on the multivariate analysis, CMR weighted risk score was developed according to the following equation [0.005 * EDV/BSA (mL/m2) – 0.029 * LVEF (%) + 0.010 * LGE ischemic mass (g)]. A multiparametric CMR weighted predictive derived score effectively identifies subjects at high risk for MAACE as compared to TTE-LVEF cut-off of 35% with a Continuous NRI: 31.7% (95%CI: 8.6%-54.8%, p=0.007) (Figure 1, Figure 2). Conclusions In this large multicenter registry, a multi-parametric CMR predictive model provides additional prognostic stratification for MAACE predictions in a large cohort of ICM patients as compared to standard of care. This model identifies a large number of patients with TTE-LVEF<35% at low risk of SCD event and on the other side it identifies a subset of patients who are at high risk of MAACE despite TTE-LVEF≥35% (i.e. the population currently not fulfilling the guideline-based criteria for ICD implantation). Further randomized trials to test a CMR guided strategy for ICD implantation versus standard of care are now needed.Kaplan-Meier curvesEvent rate redistribution

Moderate functional mitral regurgitation: difference between atrial and ventricular mechanism of the regurgitation

Abstract Background/Introduction In severe functional mitral regurgitation (MR), further distinction of the mechanism of MR in atrial functional MR (aFMR) and ventricular functional MR (vFMR) has shown prognostic importance. However, no data are available on moderate functional MR, whose characteristics and prognosis are largely unknown. Purpose To assess clinical and echocardiographic characteristics of patients with moderate aFMR and vFMR and their potential difference in outcome. Methods Patients with moderate functional MR were retrospectively included. aFMR was defined as isolated mitral annulus dilatation in combination with preserved left ventricular ejection fraction (LVEF≥50%) without ischemic heart disease or LV dilatation. Patients were classified as vFMR when LVEF was reduced, LV was dilated and/or wall motion abnormalities were present. Mitral valve intervention and all-cause mortality were used as combined endpoint. Results In total 474 patients with moderate functional MR (mean age 67 ±12, 57% male) were evaluated, of which 136 (29%) had aFMR and 338 (71%) had vFMR as underlying mechanism. Among the clinical variables, patients with aFMR had more atrial fibrillation (77% vs. 35%; p<0.001), were less symptomatic (NYHA class ≥ III: 6% vs. 18%; p<0.001) and had better renal function (eGFR 73 ±23 ml/min/1,73m2 vs. 65 ±23 ml/min/1,73m2; p=0.005) as compared to vFMR. In the vFMR group, 49% of patients had ischemic heart disease. Among the echocardiographic variables, as expected in aFMR, LVEF was higher (42 ±14% vs. 55 ±13%; p<0.001), while LV volumes (LV end-diastolic volume index 55 ±13 mL/m2 vs. 82 ±38 mL/m2; p<0.001) and E/E’ ratio were smaller (10 ±4 vs. 15 ±4; p<0.001) as compared to vFMR. However left atrial (LA) volume index was similar between both groups (43 ±14 mL/m2 vs. 41 ±18 mL/m2; p=0.271). For the echocardiographic measures of the right heart, significant difference was observed only for TAPSE which was higher for the aFMR group (22 ±4mm vs. 20 ±5mm; p<0.001). During a median follow-up of 74 months [IQR: 46.8-107.0], 132 (30%) patients died and 30 (6%) underwent mitral valve intervention. Event-free survival analysis for the combined endpoint was significantly better for aFMR patients (Figure 1). Based on significant variables from the univariable Cox regression analysis, multivariable Cox regression analysis showed that the mechanism of functional MR (with aFMR being protective as compared to vFMR), age, male gender, impaired renal function, NYHA class, severe LA dilatation and TAPSE were independently associated with the combined endpoint (Table 1). Conclusion In patients with moderate functional MR, aFMR is independently associated with better event-free survival as compared to vFMR. Therefore, clear identification of the mechanism of MR implies a better risk stratification and may be helpful for the management of patients with moderate MR.