Ventricular Reverse Remodeling Research Articles

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.

4D Flow Cardiac MR in Primary Mitral Regurgitation.

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

Effect of electroacupuncture on ventricular structure and function in rats with myocardial ischemia-reperfusion injury.

To observe the effect of electroacupuncture (EA) on changes of ventricular structure and function in rats with myocardial ischemia-reperfusion injury (MIRI), so as to explore its potential mechanisms underlying improvement of ventricular remodeling after MIRI. Forty male SD rats were randomly divided into 4 groups：sham operation group, model group, EA group and medication (sacubactril valsartan, LCZ696) group, with 10 rats in each group. The MIRI model was established by ligation of the left anterior descending coronary artery and reperfusion. EA (2 Hz/100 Hz, 2 mA) was applied to bilateral "Neiguan" (PC6) for 20 min, once every other day for 21 d. Rats of the medication group received gavage of LCZ696 (60 mg·kg-1·d-1). After the intervention, echocardiography was used to detect the ejection fraction (EF) and fractional shortening (FS) of the left ventricle, and the contents of serum tumor necrosis factor-α(TNF-α), vascular cell adhesion molecule-1(VCAM-1) and intercellular cell adhesion molecule-1(ICAM-1) were assayed by enzyme-linked immunosorbent assay. The pathological changes of myocardial tissue were observed after HE staining. The Masson staining was used to evaluate the myocardial collagen deposition and myocardial fibrosis. The mRNA expression levels of collagen Ⅰ and Ⅲ and connective tissue growth factor (CTGF) in the myocardial tissue were detected by quantitative real-time PCR, and the expression levels of IL-1β and IL-18 were detected by Western blot. In contrast to the sham operation group, the EF and FS levels of the left ventricle were ob-viously decreased (P<0.001), while the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, the expression levels of IL-1β and IL-18 were significantly increased (P<0.001, P<0.000 1, P<0.05, P<0.01) in the model group. Compared with the model group, the EF and FS levels were remarkably increased (P<0.01), whereas the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, and the expression levels of IL-1β and IL-18 were significantly down-regulated (P<0.001, P<0.01, P<0.05) in both the medication and EA groups. No significant differences were found between the EA and medication groups in all the indexes mentioned above. EA can improve the left-ventricular fibrosis and function, delay or reverse ventricular remodeling in MIRI rats, which may be related to its functions in down-regulating myocardial inflammatory response and mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF.

Long-term outcomes and reverse remodelling in recently diagnosed unexplained left ventricular systolic dysfunction.

In patients with recently diagnosed non-ischaemic LV systolic dysfunction, left ventricular reverse remodelling (LVRR) and favourable prognosis has been documented in studies with short-term follow-up. The aim of our study was to assess the long-term clinical course and stability of LVRR in these patients. We prospectively studied 133 patients (37 women; 55 [interquartile range 46, 61] years) with recently diagnosed unexplained LV systolic dysfunction, with heart failure symptoms lasting <6months and LV ejection fraction <40% persisting after at least 1week of therapy. All patients underwent endomyocardial biopsy (EMB) at the time of diagnosis and serial echocardiographic and clinical follow-up over 5years. LVRR was defined as the combined presence of (1) LVEF≥50% or increase in LVEF≥10% points and (2) decrease in LV end-diastolic diameter index (LVEDDi)≥10% or (3) LVEDDi≤33mm/m2. LVRR was observed in 46% patients at 1year, in 60% at 2years and 50% at 5years. Additionally, 2% of patients underwent heart transplantation and 12% experienced heart failure hospitalization. During 5-year follow-up, 23 (17%) of the study cohort died. In multivariate analysis, independent predictors of mortality were baseline right atrial size (OR 1.097, CI 1.007-1.196), logBNP level (OR 2.02, CI 1.14-3.56), and PR interval (OR 1.02, CI 1.006-1.035) (P<0.05 for all). The number of macrophages on EMB was associated with overall survival in univariate analysis only. LVRR at 1year of follow-up was associated with a lower rate of mortality and heart failure hospitalization (P=0.025). In multivariate analysis, independent predictors of LVRR were left ventricular end-diastolic volume index (OR 0.97, CI 0.946-0.988), LVEF (OR 0.89, CI 0.83-0.96), and diastolic blood pressure (OR 1.04, CI 1.01-1.08) (P<0.05 for all). LVRR occurs in over half of patients with recent onset unexplained LV systolic dysfunction during first 2years of optimally guided heart failure therapy and then remains relatively stable during 5-year follow-up. Normalization of adverse LV remodelling corresponds to a low rate of mortality and heart failure hospitalizations during long-term follow-up.

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

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

Kiosk 4R-FB-06 - Contemporary Heart Failure Medical Therapy Results in Significant Left Ventricular and Left Atrial Reverse Remodelling in Patients with Severe Left Ventricular Systolic Dysfunction

Kiosk 4R-FB-06 - Contemporary Heart Failure Medical Therapy Results in Significant Left Ventricular and Left Atrial Reverse Remodelling in Patients with Severe Left Ventricular Systolic Dysfunction

Kiosk 1R-TC-01 - Association Between LGE Pattern and Left Ventricular Reverse Remodeling in Dilated Cardiomyopathy

Kiosk 1R-TC-01 - Association Between LGE Pattern and Left Ventricular Reverse Remodeling in Dilated Cardiomyopathy

Left ventricular reverse remodeling after transcatheter mitral valve repair in a patient with ischemic cardiomyopathy

Left ventricular reverse remodeling after transcatheter mitral valve repair in a patient with ischemic cardiomyopathy

Long-Term Outcomes of Modified Cone Reconstruction for Ebstein's Anomaly in Pediatric Patients in a Single Center.

We aimed to investigate long-term clinical and echocardiographic outcomes, including tricuspid valve durability, annular growth, and left ventricular reverse remodeling, after modified cone reconstruction in patients with Ebstein's anomaly. This was a retrospective analysis of all pediatric patients who underwent modified cone reconstruction for Ebstein's anomaly at a single tertiary center between January 2005 and June 2021. A total of 14 pediatric patients underwent modified cone reconstruction for Ebstein's anomaly; the median age was 5.8 years (range, 0.01-16.6). There were three patients (21.4%) with Carpentier type B, ten patients with Carpentier type C (71.4%), and one patient with Carpentier type D (7.1%). There was no early or late mortality, arrhythmia, or readmission for heart failure at a 10-year follow-up. There were no cases of more than mild tricuspid stenosis or more than moderate tricuspid regurgitation during the study period, except for one patient with severe tricuspid regurgitation who underwent reoperation. The z value for tricuspid valve annular size significantly decreased immediately after the operation (2.46 vs. -1.15, p<0.001). However, from 1 year to 7 years after surgery, the z values were maintained between -1 and +1. Left ventricular end-systolic volume, end-diastolic volume, and stroke volume increased after surgery and remained elevated until seven years postoperatively. Ebstein's anomaly in children can be repaired by modified cone reconstruction with low mortality and morbidity, good tricuspid valve durability, and annular growth relative to somatic growth.

Effect of left bundle branch pacing on right ventricular function: A 3-dimensional echocardiography study

BackgroundThe effect of left bundle branch pacing (LBBP) on right ventricular (RV) function is not well known, and there is conflicting evidence regarding whether cardiac resynchronization therapy improves RV function. ObjectivesThe study aimed to investigate the effect of LBBP on RV function and to evaluate the response of RV dysfunction (RVD) to LBBP. MethodsSixty-five LBBP candidates were prospectively included in the study and underwent echocardiography at baseline and 6-month follow-up. LBBP response was left ventricular (LV) reverse remodeling, defined as a reduction in LV end-systolic volume of ≥15% at follow-up. ResultsPatients were assigned to 2 subgroups on the basis of 3-dimensional echocardiography–derived RV ejection fraction (EF) before LBBP implantation: 30 patients (46%) in the no RVD group and 35 patients (54%) in the RVD group. The RVD group was characterized by higher N-terminal pro–brain natriuretic peptide levels, New York Heart Association functional class, and larger LV/RV size. LBBP induced a significant reduction in QRS duration, LV size, and improvement in LVEF and mechanical dyssynchrony in both the no RVD and RVD groups, and a significant improvement in RV volumes and RVEF in the RVD group (all P<.01). LBBP resulted in a similar percentage reduction in QRS duration, LV dimensions, LV volumes, and percentage improvement in LVEF in RVD and no RVD groups (all P＞.05). LV reverse remodeling (29 of 35 patients vs 27 of 30 patients; P = .323) in the RVD group was similar to that in the no RVD group after LBBP. ConclusionLBBP induces excellent electrical and mechanical resynchronization, with a significant improvement in RV volumes and function. RVD did not diminish the beneficial effects on LV reverse remodeling after LBBP.

Coronary Microvascular Dysfunction in Patients With Heart Failure: Characterization of Patterns in HFrEF Versus HFpEF.

Coronary microvascular dysfunction (CMD) is involved in heart failure (HF) onset and progression, independently of HF phenotype and obstructive coronary artery disease. Invasive assessment of CMD might provide insights into phenotyping and prognosis of patients with HF. We aimed to assess absolute coronary flow, absolute microvascular resistance, myocardial perfusion, coronary flow reserve, and microvascular resistance reserve in patients with HF with preserved ejection fraction and HF with reduced ejection fraction (HFrEF). Single-center, prospective study of 56 consecutive patients with de novo HF with nonobstructive coronary artery disease divided into HF with preserved ejection fraction (n=21) and HFrEF (n=35). CMD was invasively assessed by continuous intracoronary thermodilution and defined as coronary flow reserve <2.5. Left ventricular and left anterior descending artery-related myocardial mass was quantified by echocardiography and coronary computed tomography angiography. Myocardial perfusion (mL/min per g) was calculated as the ratio between absolute coronary flow and left anterior descending artery-related mass. Patients with HFrEF showed a higher left ventricular and left anterior descending artery-related myocardial mass compared with HF with preserved ejection fraction (P<0.010). Overall, 52% of the study population had CMD, with a similar prevalence between the 2 groups. In HFrEF, CMD was characterized by lower absolute microvascular resistance and higher absolute coronary flow at rest (functional CMD; P=0.002). CMD was an independent predictor of a lower rate of left ventricular reverse remodeling at follow-up. In patients with HF with preserved ejection fraction, CMD was mainly due to higher absolute microvascular resistance and lower absolute coronary flow during hyperemia (structural CMD; P≤0.030). Continuous intracoronary thermodilution allows the definition and characterization of patterns with distinct CMD in patients with HF and could identify patients with HFrEF with a higher rate of left ventricular reverse remodeling at follow-up.

The predictive value of coronary microvascular dysfunction for left ventricular reverse remodelling in dilated cardiomyopathy.

To evaluate the degree of coronary microvascular dysfunction (CMD) in dilated cardiomyopathy (DCM) patients by cardiac magnetic resonance (CMR) first-pass perfusion parameters and to examine the correlation between myocardial perfusion and left ventricle reverse remodelling (LVRR). In this study, 94 DCM patients and 35 healthy controls matched for age and sex were included. Myocardial perfusion parameters, including upslope, time to maximum signal intensity (Timemax), maximum signal intensity (SImax), baseline signal intensity (SIbaseline), and the difference between maximum and baseline signal intensity (SImax-baseline) were measured. Additionally, left ventricular (LV) structure, function parameters, and late gadolinium enhancement (LGE) were also recorded. The parameters were compared between healthy controls and DCM patients. Univariable and multivariable logistic regression analyses were used to determine the predictors of LVRR. With a median follow-up period of 12 months [interquartile range (IQR), 8-13], 41 DCM patients (44%) achieved LVRR. Compared with healthy controls, DCM patients presented CMD with reduced upslope, SIbaseline, and increased Timemax (all p < 0.01). Timemax, SImax, and SImax-baseline were further decreased in LVRR than non-LVRR group (Timemax: 60.35 [IQR, 51.46-74.71] vs. 72.41 [IQR, 59.68-97.70], p = 0.017; SImax: 723.52 [IQR, 209.76-909.27] vs. 810.92 [IQR, 581.30-996.89], p = 0.049; SImax-baseline: 462.99 [IQR, 152.25-580.43] vs. 551.13 [IQR, 402.57-675.36], p = 0.038). In the analysis of multivariate logistic regression, Timemax [odds ratio (OR) 0.98; 95% confidence interval (CI) 0.95-1.00; p = 0.032)], heart rate (OR 1.04; 95% CI 1.01-1.08; p = 0.029), LV remodelling index (OR 1.73; 95% CI 1.06-3.00; p = 0.038) and LGE extent (OR 0.85; 95% CI 0.73-0.96; p = 0.021) were independent predictors of LVRR. CMD could be found in DCM patients and was more impaired in patients with non-LVRR than LVRR patients. Timemax at baseline was an independent predictor of LVRR in DCM.

Efficacy and safety of sacubitril/valsartan after six months in patients with heart failure with reduced ejection fraction and asymptomatic hypotension.

It is not clear whether sacubitril/valsartan is beneficial for patients with heart failure (HF) with reduced ejection fraction (HFrEF) and low systolic blood pressure (SBP). This study aimed to investigate the efficacy and tolerability of sacubitril/valsartan in HFrEF patients with SBP < 100 mmHg. An observational study was conducted on 117 patients, 40.2% of whom had SBP < 100 mmHg without symptomatic hypotension, and 59.8% of whom had SBP ≥ 100 mmHg in an optimized HF follow-up management system. At the 6-month follow-up, 52.4% of patients with SBP < 100 mmHg and 70.0% of those with SBP ≥ 100 mmHg successfully reached the target dosages of sacubitril/valsartan. A reduction in the concentration of N-terminal pro-B-type natriuretic peptide was similar between patients with SBP < 100 mmHg and SBP ≥ 100 mmHg (1627.5 pg/mL and 1340.1 pg/mL, respectively; P = 0.75). The effect of sacubitril/valsartan on left ventricular ejection fraction was observed in both SBP categories, with a 10.8% increase in patients with SBP < 100 mmHg (P < 0.001) and a 14.0% increase in patients with SBP ≥ 100 mmHg (P < 0.001). The effects of sacubitril/valsartan on SBP were statistically significant and inverse across both SBP categories (P = 0.001), with an increase of 7.5 mmHg in patients with SBP < 100 mmHg and a decrease of 11.5 mmHg in patients with SBP ≥ 100 mmHg. No statistically significant differences were observed between the two groups in terms of the occurrence of symptomatic hypotension, deteriorating renal function, hyperkalemia, angioedema, or stroke. Within an optimized HF follow-up management system, sacubitril/valsartan exhibited excellent tolerability and prompted left ventricular reverse remodeling in patients with HFrEF who presented asymptomatic hypotension.

The role of extracellular volume fraction in predicting left ventricular reverse remodelling and adverse outcomes in patients with non-ischemic cardiomyopathy and reduced left ventricular ejection fraction

The role of extracellular volume fraction in predicting left ventricular reverse remodelling and adverse outcomes in patients with non-ischemic cardiomyopathy and reduced left ventricular ejection fraction

Association of echocardiography-derived hemodynamic force parameters with left ventricular reverse remodeling after cardiac resynchronization in non-ischemic cardiomyopathy

Abstract Background Cardiac resynchronization therapy (CRT) improves outcome in selected heart failure patients and can induce left ventricular (LV) reverse remodeling. Echocardiography-derived hemodynamic forces (HDF) are a new clinical tool which provides insight in fluid dynamics. Purpose To evaluate whether baseline HDF parameters are associated with LV reverse remodeling at six months after CRT implantation in patients with non-ischemic cardiomyopathy. Methods From a CRT database, patients with LV ejection fraction &amp;lt;35%, QRS duration &amp;gt;130ms and left bundle branch block were included. At baseline, the following HDF parameters were measured for the complete heart cycle (Figure 1): 1) apical-basal strength, representing the magnitude of the longitudinal HDF, 2) lateral-septal strength, representing the magnitude of the transversal HDF and 3) the angle, representing the HDF orientation. In the systolic thrust (i.e. the positive part of systole in the apical-basal curve), the apical-basal impulse (AB impulse) and the systolic angle were measured. LV reverse remodeling was defined as a reduction of LV end-systolic volume ≥15% at six months. Results In total, 196 patients were included (age 64±11 years, 62% male). LV reverse remodeling was observed in 136 (69%) patients (i.e. responders). Baseline characteristics are presented in Table 1. Responders had a higher angle in the complete heart cycle (67.1 vs 64.1; p = 0.002) as compared to non-responders, indicating less deviation of HDF orientation in responders. Responders also had a higher AB impulse (5.0% vs. 3.4%, p = 0.012) and higher systolic angle (74.0 vs. 71.0), p&amp;lt;0.001), indicating larger magnitude of HDF and less deviation of HDF orientation in the systolic thrust. Univariable logistic regression showed a significant association of loop diuretic use, LV global longitudinal strain (LV GLS), left atrial volume index (LAVI), the angle, AB impulse and the systolic angle with LV reverse remodeling. To minimize collinearity, two multivariable models were built. Loop diuretic use, LV GLS, LAVI and AB impulse were inserted in both models, while the angle was inserted in the first model and the systolic angle in the second model. In the first model, the angle (HR 1.082 (95%CI 1.018, 1.150), p = 0.011) was independently associated with LV reverse remodeling while the systolic angle (HR 1.073 (95%CI 1.011, 1.140), p = 0.021) was independently associated with LV reverse remodeling in the second model. Conclusion At baseline, responders have better orientation of HDF in the complete heart cycle and larger magnitude and better orientation of HDF in the systolic thrust as compared to non-responders. The orientation of HDF in the complete heart cycle and systolic thrust is independently associated with LV reverse remodeling. As such, the angle and systolic angle of HDF have the potential to identify patients that are likely to experience LV reverse remodeling after CRT.Figure 1.HDF in non-ischemic CMPTable 1.Baseline characteristics

Associations of 2013 and 2021 ESC definitions of left bundle-branch block with mechanical dyssynchrony and CRT-induced reverse remodeling

Abstract Background In 2021, a new and stricter ECG-based definition of LBBB was proposed and implemented in the European Society of Cardiology (ESC) guidelines on cardiac pacing and cardiac resynchronization therapy (CRT). Aim To investigate the association between the 2021 and the 2013 LBBB definitions with CRT-induced left ventricular (LV) reverse remodeling, as well as mechanical dyssynchrony. Methods CRT patients (n=191) were retrospectively investigated. Pre-CRT digitally stored ECGs were analyzed and categorized according to the LBBB definition of 2013 (LBBB-2013) and the 2021 (LBBB-2021). Mechanical dyssynchrony (Dyss) was assessed pre-CRT using 2D-echocardiography and was defined as the presence of apical rocking and/or septal flash. CRT-induced LV reverse remodeling was measured as the relative change of left ventricular end systolic volume (LVESV) at 12 ± 6 months after CRT compared to baseline. Results Patients’ characteristics were as follows; age 70 ± 10 years, 69% males and NYHA class 2.7 ± 0.5. QRS width was 156 ± 18 ms and LVEF 33 ± 11%, and 52% had ischemic etiology. Dyss was present in 59% of the population. The percentage of the cohort that was considered to have LBBB was considerably lower according to the LBBB-2021 than according to the LBBB-2013 (18 vs. 57% respectively). Similarly, percentages of patients with LBBB+Dyss were 16 and 46% according to LBBB-2021 and LBBB-2013 respectively, with a respective Kappa coefficient of 0.16 and 0.47 (Figure A). At CRT follow up, LBBB-2013 patients showed significantly more LV reverse remodeling compared to non-LBBB patients (P &amp;lt; 0.001), while there was no significant difference between patients with LBBB-2021 and non-LBBB (P = 0.09, Figure B). Conclusion The LBBB definition proposed in the 2021 ESC guidelines excludes many patients from a class I indication for CRT. It is less associated with mechanical dyssynchrony and with CRT-induced LV reverse remodeling than the 2013 LBBB definition. Therefore, the new LBBB definition appears to be counterproductive with regards to selection of CRT patients.

Transcatheter mitral valve repair and its impact on reverse right ventricular remodelling

Abstract Introduction Transcatheter edge-to-edge repair (TEER) has been proven to reduce cardiovascular events in a particular subset of patients with severe mitral insufficiency (MR) and left ventricle dysfunction. Nevertheless, its short and long-term impact on the right ventricle (RV) remained to be determined. Our goal was to assess the effect of TEER on the RV and right chamber pressures. Methods Patients were consecutively enrolled from Nov 2018 to Jul 2022. Clinical, laboratory echocardiographic and procedural data were collected. Follow-up information of admissions for heart failure, New York Heart Association (NYHA) functional class and survival was collected. The data was analysed prior to and at 3 and 12 months after the procedure. RV dysfunction was defined as Tricuspid Annular Plane Systolic Excursion (TAPSE) &amp;lt; 17mm or S’ &amp;lt; 9cm/s. Changes between baseline and follow-up parameters were assessed using the paired t-test. Results A total of 46 patients were included. Average age was 77.28 ± 7.92 years and 30 were male (65.2%). Twelve patients were on NYHA class III (26.1%) and most had functional mitral insufficiency (25; 54.3%) and mild to moderate tricuspid insufficiency (36; 78.3%). All patients had severe mitral insufficiency (estimated regurgitant orifice area 41.28 ± 16.77mm; regurgitant volume 62 ± 28.96mL). Seventeen patients had diabetes (37.0%), 10 had coronary artery disease (21.7%), 23 had atrial fibrillation (50.0%) and 6 had chronic kidney disease (13.0%). At 3 months, mean right ventricular/right atrial gradient (RV/RAgrad) was significantly lower (37.26 ± 9.66 mmHg vs 30.81 ± 17.36 mmHg; p 0.017) as well as MR (2.98 ± 0.15 vs 1.67 ± 0.63; p &amp;lt; 0.001). There were no differences regarding severity of tricuspid regurgitation (TR) and RV and left ventricle (LV) function. At 1 year follow-up there was a marked improvement of RV/RAgrad (37.49 ± 10.87 mmHg vs 28.12 ± 10.13 mmHg; p 0.009), TAPSE (18.83 ± 4.22 mm vs 20.88 ± 3.08 mm; p 0.035), S’ (10.81 ± 4.00 cm/s vs 13.5 ± 1.97 cm/s, p 0.015) and MR severity (2.98 ± 0.15 vs 1.83 ± 0.71; p &amp;lt;0.001). Number of heart failure readmissions was also lower at 1 year follow-up post TEER (0.35 ± 0.80 vs 0.81 ± 0.87; p 0.032). Over a mean follow-up time of 1.72 ± 1.16 years, only 8.7% of patients died and 17.4% were readmitted due to heart failure. Conclusion TEER has a positive impact on right ventricle function and pressures. This effect was more prominent at 1 year follow-up and suggests reverse remodelling continues even after 3 months. Overall, patients with TEER had low rates of death and heart failure readmissions.

Myocardial DNA damage combined with genotype predicts heart failure outcome in various underlying diseases

Abstract Background Reliable predictors of treatment efficacy in heart failure have been long awaited. DNA damage has been implicated as a cause of heart failure. Purpose To investigate the association of DNA damage in myocardial tissue with treatment response and prognosis of heart failure from various etiologies; and to elucidate the relationships between genotypes and DNA damage, as well as their additive effect in prognosis prediction. Methods We performed immunostaining of DNA damage markers, poly(ADP-ribose) (PAR) and γ-H2A.X on biopsy specimens from 175 patients with heart failure with reduced ejection fraction (HFrEF) of various underlying etiologies. We calculated the percentage of nuclei positive for each DNA damage marker (%PAR and %γ-H2A.X). The primary outcome was left ventricular reverse remodeling (LVRR) at ∼1 year. The secondary outcome was a composite of cardiovascular death, heart transplantation, and ventricular assist device implantation. Whole-exome data from consenting patients were further analyzed to classify pathogenic/likely pathogenic (P/LP) variants in cardiomyopathy-related genes. We compared the degree of DNA damage among different genotypes, and examined the additive effect of combining DNA damage markers and genotypes in predicting treatment response. Results The participants had a mean age of 56 years, of whom 72% were men. Among them, 55% achieved LVRR at ∼1 year. Patients who did not achieve LVRR after the optimization of medical therapies presented with significantly higher %PAR and %γ-H2A.X when compared with those who did [%PAR, 11 (6–19) % vs. 2 (1–4) %, P &amp;lt; 0.001; %γ-H2A.X, 22 (11–40) % vs. 5 (2–9) %, P &amp;lt; 0.001] (Figure, left bottom). The receiver-operating characteristic (ROC) analysis demonstrated good performance of both %PAR and %γ-H2A.X for predicting LVRR (area under the curve 0.87 and 0.85, respectively). Patients with lower %PAR or %γ-H2A.X had reduced long-term clinical events [PAR, hazard ratio 1.63 (95%CI 1.31- 2.01), P &amp;lt; 0.001; γ-H2A.X, 1.48 (1.27-1.72), P &amp;lt; 0.001] (Figure, left bottom). In addition, there was a strong negative correlation between the mean proportion of DNA damage marker positive nuclei and the probability of LVRR, across different underlying diseases (Figure, middle). Genotypes were identified in 105 patients (Figure, right top). Non-sarcomeric mutation (LMNA, etc) carriers presented with more pronounced DNA damage than sarcomeric mutation carriers (TTN, MYBPC3) (Figure, right bottom). Combination of genotypes and %γ-H2A.X augmented the area under the ROC for predicting 1-year LVRR to 0.90, from that of %γ-H2A.X alone at 0.85. Conclusions The degree of DNA damage accumulation in myocardial tissue differs by underlying diseases and genotypes, and determines the consequences of human heart failure. Assessment of DNA damage, especially when combined with genotype, is useful to predict treatment efficacy and prognosis of HFrEF patients with various underlying etiologies.graphical abstract

The predictive role of left ventricular cathode topography relative to CMR-determined latest mechanical activation and scar segments on response to cardiac resynchronisation therapy

Abstract Background Cardiac resynchronisation therapy (CRT) is still burdened by considerable rates of non-response. Herein left ventricular cathode (LVC) positioning has the greatest room for optimisation. Nonetheless, a purely CMR-based approach exploring LVC topography relative to both mechanical delay and tissue viability is yet to be investigated. Purpose To retrospectively analyse the effect on reverse remodelling of CMR-determined LVC topography relative to latest mechanical activation (LMA) and scar segments in a CRT population. Methods This is a retrospective single-centre analysis of 104 CRT-D/P consecutive patients with CMR performed within 6 months before implantation. Electrical delay (Q-LV time) was mapped on all suitable veins with LV lead positioning and cathode programming set in the region of latest electrical activation. Through CART-Tech® software analysis of CMR images, 36-segment 3D anatomical models of radial strain and scar were superimposed on their corresponding fluoroscopy images (Figure 1). Patients were then stratified based on LVC concordance (within), semi-concordance (adjacent) or non-concordance (at least one segment away) with LMA and scar segments (defined as segments with &amp;gt;50% scar transmurality). Follow-up echocardiography was performed at least 6 months after implantation and the degree of reverse remodelling expressed as percentage reduction in end-systolic volume (ESV). Results Of the 104 patients, 36 were excluded due to suboptimal CMR quality (8), switch to conduction system pacing (5), loss to follow-up (18) or death within 6 months of implantation (5), leaving a total of 68 (63 CRT-D and 5 CRT-P). LVC concordance with LMA was associated with a statistically significant improvement in reverse remodelling (Figure 2, A), while the contrary occurred with regards to scar (Figure 2, B). A greater impact of distance from scar compared to LMA proximity was observed, thus a combined analysis of LVC topography relative to both was developed accordingly. Patients were stratified into 4 categories of LVC optimality: optimal (LVC-LMA concordance + LVC-scar non-concordance), semi-optimal (LVC-LMA semi-concordance + LVC-scar non-concordance), suboptimal (LVC-LMA non-concordance + LVC-scar non-concordance), and unfavourable (LVC-scar semi-concordance or concordance regardless of LVC-LMA). The unfavourable group had higher rates of atrial fibrillation, non-LBBB QRS morphology and higher scar burden, while no significant differences were observed in the other 3 groups. This classification appears to predict the degree of reverse remodelling, ESV reduction being more pronounced the more optimal the group (Figure 2, C). Conclusions CMR-determined LVC topography relative to LMA and scar segments predicts left ventricular reverse remodelling in Q-LV-guided CRT implants. Optimisation of CRT response may thus benefit from a CMR-based approach assessing mechanical delay and tissue viability to guide LVC positioning.Figure 1Figure 2

Predictors of left ventricular reverse remodeling after catheter ablation for atrial fibrillation: sub analysis of a randomized controlled EARNEST-PVI trial

Abstract Background Atrial fibrillation (AF) is widely known to cause heart failure. The catheter ablation for AF improves left ventricular function in many patients with heart failure. However, the predictors of left ventricular reverse remodeling are not well established. Purpose The purpose of this study was to examine the predictor of left ventricular reverse remodeling in patients with persistent AF. Methods The predictors of left ventricular reverse remodeling was examined using data from EARNEST-PVI trial which compared 12-month rhythm outcomes between persistent AF patients allocated to pulmonary vein isolation (PVI) alone and those allocated to PVI followed by left atrial linear ablation or complex fractionated electrograms ablation. Left ventricular reverse remodeling in this study was defined as a 15% reduction of left ventricular systolic diameter at transthoracic echocardiogram 12 months after initial ablation compared to preoperative echocardiogram. Results Of the 512 patients enrolled in the EARNEST-PVI trial, 453 patients with preoperative and 12-month postoperative echocardiogram data were analyzed. Median age was 67 [60. 73] years and 75.7% were male. Recurrence of AF was observed in 106 patients (23.4%) during 12 months after the ablation. LVEF before the initial ablation was 44 [39, 47]% and LVEF 12 months after the initial ablation was 60 [55, 63]% (P&amp;lt;0.001), and LVDs before the initial ablation was 30 [27, 34] mm and LVDs after the initial ablation was 29 [27, 31] mm (P&amp;lt;0.001). Left ventricular reverse remodeling was observed in 78 patients (17.2%). Multivariate linear regression analysis showed age (Odds ratio 0.967 [95%CI=0.939-0.996], P=0.025), preoperative hear rate (Odds ratio 1.032 [95%CI=1.018-1.047], P&amp;lt;0.001) and the use of β-blocker (Odds ratio 2.119 [95%CI=1.235-3.638], P=0.006) were independently associated with left ventricular reverse remodeling but AF recurrence was not (Odds ratio 0.532 [95%CI=0.425-1.561], P=0.538). Conclusion Patients with persistent AF showed improvement of LVEF and left ventricular reverse remodeling 12 months after the catheter ablation. Age, heart rate before the initial ablation and the use of β-blocker were predictive factors for the left ventricular reverse remodeling after the ablation regardless of AF recurrence.