Left atrial low-voltage areas, but not volume, predict the recurrence of atrial fibrillation in repeat ablation procedures.

INTRODUCTION: Left atrial (LA) low voltage areas (LVA) are a controversial target in atrial fibrillation ablation procedures. However, LVA and LA volume are good predictors of arrhythmia recurrence in ablation-naïve patients. Their predictive value in progressively diseased pre-ablated atria is uncertain. METHODS: Consecutive patients with recurrent atrial fibrillation (AF) or atrial tachycardia (AT), who were scheduled for repeat LA ablation, were enrolled in the prospective Bernau ablation registry between 2016 and 2020. All patients received a complete LA ultrahigh-density map before ablation. Maps were analyzed for LA size, LVA percentage and distribution. The predictive value of demographic, anatomic, and mapping variables on AF recurrence was analyzed. RESULTS: 160 patients (50.6% male, 1.3 pre-ablations, 60% persistent AF) with complete LA voltage maps were included. Mean follow-up time was 16 ± 11 months. Mean recorded electrograms (EGMs) per map were 9754 ± 5808, mean LA volume was 176.1 ± 35.9 ml and mean rate of LVAs <0.5 mV was 30.6% ± 23.1%. During follow-up recurrence rate of AF or AT >30 s was 55.6%. Patients with recurrence had a significant higher percentage of LVAs (40.0% vs. 18.8%, p < .001) but no relevant difference in LA volume (172 vs. 178 mL, p = .299). ROC curves revealed LVA as a good predictor for recurrence (AUC = 0.79, p < .001) and a cut-off of 22% LVAs with highest sensitivity (73.0%) and specificity (71.8%). Based on this cut off, event free survival was significantly higher in the Low LVA group (p < .01). CONCLUSION: Total LVA percentage has a good predictive power on arrhythmia recurrence in a cohort of advanced scarred left atria in repeat procedures independent of the applied ablation strategy. Left atrial volume seems to have minor impact on the rhythm outcome in our study cohort.

Impact of atrial fibrillation phenotype and left atrial volume on outcome after pulmonary vein isolation.

AIMS: Pulmonary vein isolation (PVI) is increasingly performed in patients with atrial fibrillation (AF). Both AF phenotype and left atrial (LA) volume have been shown to influence ablation outcome. The inter-relationship of the two is incompletely understood. We aimed to investigate the impact of AF phenotype vs. LA volume on outcome after PVI. METHODS AND RESULTS: In a retrospective analysis of a prospective registry of patients undergoing a first PVI, the association of AF phenotype and LA volume index (LAVI) was assessed as well as their impact on AF recurrence during follow-up. Overall, 476 patients were enrolled (median age 63 years, 29% females, 65.8% paroxysmal AF). Obesity, hypertension, chronic kidney disease, and heart failure were all significantly more frequent in persistent AF. After 1 year, single-procedure, freedom from arrhythmia recurrence was 61.5%. Patients with paroxysmal AF had better outcomes compared with patients with persistent AF (65.6 vs. 52.7%, P = 0.003), as had patients with no/mild vs. moderate/severe LA dilation (LAVI <42 mL/m2 67.1% vs. LAVI ≥42 mL/m2 53%, P < 0.001). The combination of both parameters refined prediction of 1-year recurrence (P < 0.001). After adjustment for additional clinical risk factors in multivariable Cox proportional hazard analysis, both AF phenotype and LAVI ≥42 mL/m2 contributed significantly towards the prediction of 1-year recurrence. CONCLUSION: Atrial fibrillation phenotype and LA volume are independent predictors of outcome after PVI. Persistent AF with no/mild LA dilation has a similar risk of recurrence as paroxysmal AF with a moderate/severe LA dilation and should be given similar priority for ablation.

Sex differences in the association between epicardial adipose tissue volume and left atrial volume index.

BACKGROUND: Sex disparities in the association between epicardial adipose tissue volume (EATV) and cardiovascular disease have been reported. The sex-dependent effects of EATV on left atrial (LA) size have not been elucidated. METHODS: Consecutive 247 subjects (median 65 [interquartile range 57, 75] years; 67% of men) who underwent multi-detector computed tomography without significant coronary artery disease or moderate to severe valvular disease were divided into two groups: patients with sinus rhythm (SR) or atrial fibrillation (AF). Sex differences in the association between the EATV index (EATVI) (mL/m2) and LA volume index (LAVI) in 63 SR (28 men and 35 women) and 184 AF (137 men and 47 women) patients were evaluated using univariate and multivariate regression analyses. RESULTS: In overall that includes both men and women, the relationship between EATVI and LAVI was not significantly correlated for patients with SR and AF. The relationship between EATVI and LAVI differed between men and women in both SR and AF groups. In SR patients, there was a positive relationship between EATVI and LAVI in men, but not in women. In contrast, in patients with AF, a negative relationship was found between EATVI and LAVI in women, whereas no association was found in men. CONCLUSIONS: We evaluated sex differences in the association between EATVI and LAVI in patients with either SR or AF, and found a positive relationship in men with SR and a negative relationship in women with AF. This is the first report to evaluate sex differences in the relationship between EATVI and LAVI, suggesting that EAT may play a role, at least in part, in sex differences in the etiology of AF.

Factors influencing post-surgical survival in degenerative mitral regurgitation.

AIMS: Indications for surgery in patients with degenerative mitral regurgitation (DMR) are increasingly liberal in all clinical guidelines but the role of secondary outcome determinants (left atrial volume index ≥60 mL/m2, atrial fibrillation, pulmonary artery systolic pressure ≥50 mmHg and moderate to severe tricuspid regurgitation) and their impact on post-operative outcome remain disputed. Whether these secondary outcome markers are just reflective of the DMR severity or intrinsically affect survival after DMR surgery is uncertain and may have critical importance in the management of patients with DMR. To address these gaps of knowledge the present study gathered a large cohort of patients with quantified DMR, accounted for the number of secondary outcome markers and examined their independent impact on survival after surgical correction of the DMR. METHODS AND RESULTS: The Mitral Regurgitation International DAtabase-Quantitative registry includes patients with isolated DMR from centres across North America, Europe, and the Middle East. Patient enrolment extended from January 2003 to January 2020. All patients undergoing mitral valve surgery within 1 year of registry enrolment were selected. A total of 2276 patients [65 (55-73) years, 32% male] across five centres met study eligibility criteria. Over a median follow-up of 5.6 (3.6 to 8.7) years, 278 patients (12.2%) died. In a comprehensive multivariable Cox regression model adjusted for age, EuroSCORE II, symptoms, left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LV ESD) and DMR severity, the number of secondary outcome determinants was independently associated with post-operative all-cause mortality, with adjusted hazard ratios of 1.56 [95% confidence interval (CI): 1.11-2.20, P = 0.011], 1.78 (95% CI: 1.23-2.58, P = 0.002) and 2.58 (95% CI: 1.73-3.83, P < 0.0001) for patients with one, two, and three or four secondary outcome determinants, respectively. A model incorporating the number of secondary outcome determinants demonstrated a higher C-index and was significantly more concordant with post-operative mortality than models incorporating traditional Class I indications alone [the presence of symptoms (P = 0.0003), or LVEF ≤60% (P = 0.006), or LV ESD ≥40 mm (P = 0.014)], while there was no significant difference in concordance observed compared with a model that incorporated the number of Class I indications for surgery combined (P = 0.71). CONCLUSION: In this large cohort of patients treated surgically for DMR, the presence and number of secondary outcome determinants was independently associated with post-surgical survival and demonstrated better outcome discrimination than traditional Class I indications for surgery. Randomised controlled trials are needed to determine if patients with severe DMR who demonstrate a cardiac phenotype with an increasing number of secondary outcome determinants would benefit from earlier surgery.

The use of dedicated long-axis views focused on the left atrium improves the accuracy of left atrial volumes and emptying fraction measured by cardiovascular magnetic resonance.

BACKGROUND: The use of apical views focused on the left atrium (LA) has improved the accuracy of LA volume evaluation by two-dimensional (2D) echocardiography. However, routine cardiovascular magnetic resonance (CMR) evaluation of LA volumes still uses standard 2- and 4-chamber cine images focused on the left ventricle (LV). To investigate the potential of LA-focused CMR cine images, we compared LA maximuml (LAVmax) and minimum (LAVmin) volumes, and emptying fraction (LAEF), calculated on both standard and LA-focused long-axis cine images, with LA volumes and LAEF obtained by short-axis cine stacks covering the LA. LA strain was also calculated and compared between standard and LA-focused images. METHODS: LA volumes and LAEF were obtained from 108 consecutive patients by applying the biplane area-length algorithm to both standard and LA-focused 2- and 4-chamber cine images. Manual segmentation of a short-axis cine stack covering the LA was used as the reference method. In addition, LA strain reservoir (εs), conduit (εe) and booster pump (εa) were calculated using CMR feature-tracking. RESULTS: Compared to the reference method, the standard approach significantly underestimated LA volumes (LAVmax: bias - 13 ml; LOA = + 11, - 37 ml; LAVmax i: bias - 7 ml/m2; LOA = + 7, - 21 ml/m2; LAVmin; bias - 10 ml, LOA: + 9, - 28 ml; LAVmin i: bias - 5 ml/m2, LOA: + 5, - 16 ml/m2), and overestimated LA-EF (bias 5%, LOA: + 23, - 14%). Conversely, LA volumes (LAVmax: bias 0 ml; LOA: + 10, - 10 ml; LAVmax i: bias 0 ml/m2; LOA: + 5, - 6 ml/m2; LAVmin: bias - 2 ml; LOA: + 7, - 10 ml; LAVmin i: bias - 1 ml/m2; LOA: + 3, - 5 ml/m2) and LAEF (bias 2%, LOA: + 11, - 7%) by LA-focused cine images were similar to those measured using the reference method. LA volumes by LA-focused images were obtained faster than using the reference method (1.2 vs 4.5 min, p < 0.001). LA strain (εs: bias 7%, LOA = 25, - 11%; εe: bias 4%, LOA = 15, - 8%; εa: bias 3%, LOA = 14, - 8%) was significantly higher in standard vs. LA-focused images (p < 0.001). CONCLUSION: LA volumes and LAEF measured using dedicated LA-focused long-axis cine images are more accurate than using standard LV-focused cine images. Moreover, LA strain is significantly lower in LA-focused vs. standard images.

Left atrial expansion index measured with cardiovascular magnetic resonance estimates pulmonary capillary wedge pressure in dilated cardiomyopathy.

BACKGROUND: Pulmonary capillary wedge pressure (PCWP) assessment is fundamental for managing dilated cardiomyopathy (DCM) patients. Although cardiovascular magnetic resonance (CMR) has become the gold-standard imaging technique for evaluating cardiac chamber volume and function, PCWP is not routinely assessed with CMR. Therefore, this study aimed to validate the left atrial expansion index (LAEI), a LA reservoir function parameter able to estimate filling pressure with echocardiography, as a novel CMR-measured parameter for non-invasive PCWP estimation in DCM patients. METHODS: We performed a retrospective, single-center, cross-sectional study. We included electively admitted DCM patients referred to our tertiary center for further diagnostic evaluation that underwent a clinically indicated right heart catheterization (RHC) and CMR within 24 h. PCWP invasively measured during RHC was used as the reference. LAEI was calculated from CMR-measured LA maximal and minimal volumes as LAEI = ( (LAVmax-LAVmin)/LAVmin) × 100. RESULTS: We enrolled 126 patients (47 ± 14 years; 68% male; PCWP = 17 ± 9.3 mmHg) randomly divided into derivation (n = 92) and validation (n = 34) cohorts with comparable characteristics. In the derivation cohort, the log-transformed (ln) LAEI showed a strong linear correlation with PCWP (r = 0.81, p < 0.001) and remained a strong independent PCWP determinant over clinical and conventional CMR parameters. Moreover, lnLAEI accurately identified PCWP ≥ 15 mmHg (AUC = 0.939, p < 0.001), and the optimal cut-off identified (lnLAEI ≤ 3.85) in the derivation cohort discriminated PCWP ≥ 15 mmHg with 82.4% sensitivity, 88.2% specificity, and 85.3% accuracy in the validation cohort. Finally, the equation PCWP = 52.33- (9.17xlnLAEI) obtained from the derivation cohort predicted PCWP (-0.1 ± 5.7 mmHg) in the validation cohort. CONCLUSIONS: In this cohort of DCM patients, CMR-measured LAEI resulted in a novel and useful parameter for non-invasive PCWP evaluation.

Late recurrence of atrial fibrillation 5 years after catheter ablation: predictors and outcome.

AIMS: Atrial fibrillation (AF) is a chronic progressive disease that continuously recurs even after successful AF catheter ablation (AFCA). We explored the mechanism of long-term recurrence by comparing patient characteristics and redo-ablation findings. METHODS AND RESULTS: Among the 4248 patients who underwent a de novo AFCA and protocol-based rhythm follow-up at a single centre, we enrolled 1417 patients [71.7% male, aged 60.0 (52.0-67.0) years, 57.9% paroxysmal AF] who experienced clinical recurrences (CRs), and divided them according to the period of recurrence: within one year (n = 645), 1-2 years (n = 339), 2-5 years (n = 308), and after 5 years (CR>5 yr, n = 125). We also compared the redo-mapping and ablation outcomes of 198 patients. In patients with CR>5 yr, the proportion of paroxysmal AF was higher (P = 0.031); however, the left atrial (LA) volume (quantified by computed tomography, P = 0.003), LA voltage (P = 0.003), frequency of early recurrence (P < 0.001), and use of post-procedure anti-arrhythmic drugs (P < 0.001) were lower. A CR>5 yr was independently associated with a low LA volume [odds ratio (OR) 0.99 (0.98-1.00), P = 0.035], low LA voltage [OR 0.61 (0.38-0.94), P = 0.032], and lower early recurrence [OR 0.40 (0.23-0.67), P < 0.001]. Extra-pulmonary vein triggers during repeat procedures were significantly greater in patients with a CR>5 yr, despite no difference in the de novo protocol (P for trend 0.003). The rhythm outcomes of repeat ablation procedures did not differ according to the timing of the CR (log-rank P = 0.330). CONCLUSIONS: Patients with a later CR exhibited a smaller LA volume, lower LA voltage, and higher extra-pulmonary vein triggers during the repeat procedure, suggesting AF progression.

Echocardiographic Parameters of Left Atrial Structure and Function and Clinical Outcomes at 2 Years in Elderly Patients With Atrial Fibrillation　- The ANAFIE Echocardiographic Substudy.

BACKGROUND: This prospective ANAFIE Registry substudy investigated the relationship between the echocardiographic parameters of left atrial (LA) structure and function and clinical outcomes at 2 years among atrial fibrillation (AF) patients aged ≥75 years.Methods and Results: Outcomes of 1,474 elderly non-valvular AF (NVAF) patients who underwent transthoracic echocardiography at baseline were analyzed by categories of maximum LA volume index (max. LAVi) and LA emptying fraction (LAEF) total. Baseline mean±standard deviation LAEF total and max. LAVi were 28.2±14.9% and 54.2±25.9 mL/m2, respectively. Proportions of oral anticoagulant (OAC), direct OAC, and warfarin use were 92.7%, 68.7%, and 24.0%, respectively. Patients with LAEF total ≤45.0% (n=1,213) vs. >45.0% (n=224) were at higher risk of cardiovascular events (hazard ratio [HR]: 2.19, P=0.021) and heart failure (HF) hospitalization (HR: 2.25, P=0.045). Risk of all-cause death was higher with max. LAVi >48.0 mL/m2(n=656) vs. ≤48.0 mL/m2(n=621) (HR: 1.69, P=0.048). Subgroups with abnormal LA function and structure had increased incidence of cardiac/cardiovascular events and HF hospitalization. No significant interaction was observed between echocardiographic parameters and OAC type. CONCLUSIONS: Elderly Japanese patients with NVAF and LAEF total ≤45.0% were at higher risk of cardiovascular events and HF hospitalization, and those with max. LAVi >48.0 mL/m2were at higher risk of all-cause death.

Early predicting improvement of severe systolic heart failure by left atrial volume.

Left atrium (LA) modulates left ventricle (LV) filling and cardiac performance. We aimed to assess the effect of heart failure (HF) therapy on LA and LV function, and the relationship between LA/LV improvement and clinical outcome in acute HF with reduced LV ejection fraction (LVEF). Totally, 224 hospitalized patients with acute HF and LVEF < 35% were enrolled and underwent echocardiography. They all received maximal tolerable doses of evidence-based medications. Patients received echocardiographic measurements at each visit including stroke volume, LVEF, LA minimal/maximal volume (LAVmin/LAVmax), LA expansion index, and tissue Doppler parameters. The threshold of LV functional improvement was LVEF > 45% ever occurred before study end. During the mean follow-up of 6.3 years, 62 cases improved well, mean LVEF 49 ± 5% at study end. The reduction of LV filling pressure occurring as early as 2 weeks later, LV systolic function improvement took longer (> 1 month). The reductions in LAVmin and LAVmax between initial stabilization and 2 weeks after HF treatment (Initial-2 W) and the increase of LA expansion index (Initial-2 W) were associated independently with LVEF improvement (p 0.002, 0.006, and 0.007, respectively). The best predictor of LVEF improvement was LAVmin reduction (Initial-2 W) > 5 ml with 77% sensitivity, 76% specificity. Cox proportional hazard regression analyses for cardiovascular events revealed LVEF improvement reduced 74% of events (hazard ratio 0.264, 95% CI 0.192-0.607, p < 0.0001); and LA expansion index (per 1% increase) reduced 14% of events (hazard ratio 0.862, 95% CI 0.771-0.959, p < 0.0001). The early reduction of LAV (Initial-2 W), especially LAVmin, is a powerful early predictor of LVEF improvement. Its occurrence reduces cardiovascular events significantly. ClinicalTrials.gov number: NCT01307722.

Left-atrial volume reduction reflects improvement of cardiac sympathetic nervous function in patients with severe aortic stenosis after transcatheter aortic valve replacement.

Trans-catheter aortic valve replacement (TAVR) is an excellent alternative intervention for surgical aortic valve replacement. Cardiac sympathetic nervous (CSN) function and left atrial (LA) volume are both important prognostic factors in patients with aortic stenosis (AS) after TAVR. The relationship between the two clinical factors is unknown, however. This retrospective observational study aimed to assess the correlation between CSN function and LA volume in 48 symptomatic patients with severe AS (median age: 85 years, IQR 82-88 years; 81% female) before and after TAVR. CSN function was assessed by performing 123I-metaiodobenzylguanidine (MIBG) scintigraphy before and 6 months after TAVR, and the delayed heart-to-mediastinum ratio (dHMR) and washout rate (WR) were calculated. We also performed transthoracic echocardiography near the same time. TAVR improved the dHMR, WR, and LA volume index (LAVI) (dHMR: median 2.89 [IQR 2.62-3.23] vs. 2.98 [2.49-3.25], p = 0.0182; WR: 28% [24-38] vs. 23% [16-32], p < 0.0001; LAVI: 47.7 mL/m2 [37.8-56.3] vs. 41.2 mL/m2 [33.7-56.1], p = 0.0024). In multiple linear regression analysis, the percentage change in LAVI from baseline to post-TAVR (∆LAVI%) was an independent predictor of change in dHMR from baseline to post-TAVR (ß = - 0.35, p = 0.0110). In conclusion, LA volume reduction reflected CSN functional improvement after TAVR. In patients with TAVR, ∆LAVI% might be a valuable parameter for evaluating CSN functional recovery.

Resting echocardiographic parameters can exclude significant coronary artery disease: A comparison with coronary computed tomography angiography.

INTRODUCTION: Coronary computed tomography angiography (CCTA) is known to have a high negative predictive value (NPV) in identifying coronary artery disease (CAD). This study aimed to examine whether resting echocardiographic parameters could exclude significant CAD on CCTA. METHODS: We recruited 142 patients who had undergone both CCTA and echocardiography within a 3-month window. Based on the CCTA findings, patients were divided into two groups: Group A (non-significant CAD, defined as all coronary segments having <50% stenosis) and Group B (significant CAD). Resting echocardiographic parameters were compared between the two groups to identify predictors of non-significant CAD on CCTA. RESULTS: A total 92 patients (mean age, 68 ± 13 years; males, 62%) were eligible for this study; 50 in Group A and 42 in Group B. Among the various echo parameters, left atrial volume index (LAVI) and left ventricular (LV) global longitudinal strain (GLS) were significantly lower in Group A (23.5 ± 7.6 vs. 33.6 ± 7.4 mL/m2 , p < .001; -20.2 ± 1.8% vs. -16.8 ± 2.0%, p < .001, respectively). Analysis of the receiver operating characteristic curve revealed that the cutoff value to exclude significant CAD on CCTA was 29.0 mL/m2 for LAVI (NPV 80.8%) and -18.1% for GLS (NPV 80.7%). The NPV increased to 95.0% when these parameters were combined (LAVI < 29.0 mL/m2 and GLS < -18.1%). CONCLUSION: The combination of resting LAVI and GLS was clinically useful in excluding significant CAD via CCTA.

Non-Alcoholic Fatty Liver Disease and Echocardiographic Parameters of Left Ventricular Diastolic Function: A Systematic Review and Meta-Analysis.

The cardiovascular implications of non-alcoholic fatty liver disease (NAFLD) have been associated with heart failure with preserved ejection fraction (HFpEF). The purpose of this review was to conduct a bibliographic search regarding the correlation between NAFLD and the echocardiographic parameters of left ventricular diastolic function. A systematic literature search was conducted in PubMed and Embase for original research data reporting on the association of NAFLD with diastolic function markers [E/e', left atrial volume index (LAVi), left ventricular mass index (LVMi)]. Meta-analysis was performed using the meta and dmetar packages in R studio v.1.4.1106, with p < 0.05 values being considered significant. Results are expressed as the standardized mean difference (SMD) for continuous variables and as the odds ratio (OR) for categorical variables, with respective 95% confidence intervals (CI). Heterogeneity between studies was expressed with index Ι2. From the preliminary search, 2619 articles were found from which 31 studies were included in the final statistical analysis. The meta-analysis of 8 studies which reported on the prevalence of diastolic dysfunction showed that it was increased in patients with NAFLD (OR: 2.07, 95% CI 1.24-3.44 with p = 0.01, I2: 80% with p < 0.01). The meta-analysis of 21 studies showed significantly higher E/e' in NAFLD patients (SMD 1.02, 95% CI 0.43-1.61 with p < 0.001, I2: 97% with p < 0.001). Individuals with NAFLD had increased LAVi (SMD: 0.87, 95% CI 0.38-1.37 with p < 0.001, I2: 96% with p < 0.001) and LVMi (SMD: 0.89, 95% CI 0.31-1.48 with p = 0.003, I2: 100% with p < 0.001). To conclude, in the meta-analysis of 31 observational studies, NAFLD patients were found to have affected left ventricular diastolic function, supporting the hypothesis of NAFLD being associated with HFpEF.

Impact of Structural Abnormalities in Left Ventricle and Left Atrium on Clinical Outcomes in Heart Failure with Preserved Ejection Fraction.

Two key echocardiographic parameters, left ventricular mass index (LVMI) and left atrial volume index (LAVI), are important in assessing structural myocardial changes in heart failure (HF) with preserved ejection fraction (HFpEF). However, the differences in clinical characteristics and outcomes among groups classified by LVMI and LAVI values are unclear.We examined the data of 960 patients with HFpEF hospitalized due to acute decompensated HF from the PURSUIT-HFpEF registry, a prospective, multicenter observational study. Four groups were classified according to the cut-off values of LVMI and LAVI [LVMI = 95 g/m2 (female), 115 g/m2 (male) and LAVI = 34 mL/m2]. Clinical endpoints were the composite of HF readmission and all-cause death. Study endpoints among the 4 groups were evaluated. The composite endpoint occurred in 364 patients (37.9%). Median follow-up duration was 445 days. Kaplan-Meier analysis revealed significant differences in the composite endpoint among the 4 groups (P < 0.001). Cox proportional hazards analysis demonstrated that patients with increased LAVI alone were at significantly higher risk of HF readmission and the composite endpoints than those with increased LVMI alone (P = 0.030 and P = 0.024, respectively). Age, male gender, systolic blood pressure at discharge, atrial fibrillation (AF) hemoglobin, renal function, and LAVI were significant determinants of LVMI and female gender, AF, hemoglobin, and LVMI were significant determinants of LAVI.In HFpEF patients, increased LAVI alone was more strongly associated with HF readmission and the composite of HF readmission and all-cause death than those with increased LVMI alone.

The impact of SGLT2 inhibition on imaging markers of cardiac function: A systematic review and meta-analysis.

OBJECTIVES: The use of sodium-glucose cotransporter-2 inhibitors (SGLT2-Is) has resulted in significant benefits in patients with heart failure irrespective of left ventricular ejection fraction (LVEF) and the presence of diabetes mellitus. The aim of this systematic review and meta-analysis was to assess the impact of SGLT2-Is on cardiac function indices. METHODS: We conducted a systematic literature search for studies assessing the changes in LVEF, global longitudinal strain (GLS), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular mass index (LVMi), left atrial volume index (LAVi), and E/e' following the initiation of an SGLT2-I. RESULTS: A total of 32 studies with 2351 patients were included. SGLT2 inhibition resulted in a significant improvement of LVEF [MD 1.97 (95%CI 0.92, 3.02), p < .01, I2:84%] in patients with heart failure, an increase in GLS [MD 1.17 (95% CI 0.25, 2.10), p < .01], a decrease in LVESV [MD: -3.60 (95% CI -7.02, -0.18), p = .04, I2:9%] while the effect was neutral concerning LVEDV [MD: -3.10 (95% CI -6.76, 0.56), p = .40, I2:4%]. LVMi [MD: -3.99 (95% CI -7.16 to -0.82), p = .01, I2:65%], LAVi [MD: -1.77 (95% CI -2.97, -0.57), p < .01, I2:0%], and E/e' [MD: -1.39 (95% CI -2.04, -0.73), p < .01, I2:55%] were significantly reduced. CONCLUSIONS: In this systematic review and meta-analysis, the use of SGLT2 inhibitors was associated with an improvement in markers of cardiac function, confirming the importance of SGLT2 inhibition towards the reversal of cardiac remodeling.

Elevated plasma Ninjurin-1 levels in atrial fibrillation is associated with atrial remodeling and thromboembolic risk.

BACKGROUND: Nerve injury-induced protein 1 (Ninj1) is elevated in various inflammatory diseases. The soluble form of Ninj1 yield by matrix metalloproteinase cleavage is a secreted protein and inhibits cell adhesion and inflammation. However, the role of plasma Ninj1 in atrial fibrillation (AF) has not been reported. The present study aimed to investigate the correlation between plasma Ninj1 levels and AF. METHODS: A total of 96 AF patients [age 66.00 (60.00, 72.00) years, male 56 (58.33%)] and 51 controls without AF [age 65.00 (55.00, 68.00) years, male 21 (41.18%)] were enrolled in this study. Plasma Ninj1 concentrations were detected using enzyme-linked immunosorbent assay. Also, the clinical characteristics, left atrial volume index (LAVI), CHA2DS2-VASc score, and HAS-BLED score were evaluated. RESULTS: Plasma Ninj1 levels were significantly higher in patients with AF than in controls (P < 0.001). Plasma Ninj1 levels were positively correlated with LAVI (P = 0.019) and CHA2DS2-VASc score (P = 0.024). Logistic regression analysis confirmed that the Ninj1 plasma levels were associated with AF (P = 0.009). The receiver operating characteristic analysis showed that plasma Ninj1 had a predictive value for AF (P < 0.001). CONCLUSIONS: Plasma Ninj1 levels were elevated in patients with AF, associated with left atrial enlargement and thromboembolic risk in AF.

Circulating biomarker correlates of left atrial size and myocardial extracellular volume fraction among persons living with and without HIV.

BACKGROUND: Infection with human immunodeficiency virus (HIV) is associated with higher risk for myocardial disease despite modern combination antiretroviral therapy (cART). Factors contributing to this excess risk, however, remain poorly characterized. We aimed to assess cross-sectional relationships between elevations of left atrial volume index (LAVI) and myocardial extracellular volume (ECV) fraction that have been reported in persons living with HIV and levels of circulating biomarkers of inflammation, fibrosis, and myocyte stretch among persons living with and without HIV (PLWH, PLWOH). METHODS: Participants from three cohorts of PLWH and PLWOH underwent cardiovascular magnetic resonance imaging for measurement of LAVI and ECV. Levels of circulating proteins (IL-6, sCD14, galectin-3, NT-proBNP, GDF-15, TIMP-2, MMP-2, and hsTnI) were measured using immunoassays. Associations were assessed using logistic and linear regression, adjusting for demographics, substance use, and clinical characteristics. RESULTS: Among 381 participants with and without HIV, median age (IQR) was 55.1 (51.2, 58.4) years, 28% were female, 69% were Black, and 46% were current smokers. Sixty-two percent were PLWH (n = 235), of whom 88% were receiving cART and 72% were virally suppressed. PLWH had higher levels of sCD14 (p = < 0.001), GDF-15 (p = < 0.001), and NT-proBNP (p = 0.03) compared to PLWOH, while levels of other biomarkers did not differ by HIV serostatus, including IL-6 (p = 0.84). Among PLWH, higher sCD14, GDF-15, and NT-proBNP were also associated with lower CD4 + cell count, and higher NT-proBNP was associated with detectable HIV viral load. NT-proBNP was associated with elevated LAVI (OR: 1.79 [95% CI: 1.31, 2.44]; p < 0.001) with no evidence of effect measure modification by HIV serostatus. Other associations between HIV-associated biomarkers and LAVI or ECV were small or imprecise. CONCLUSIONS: Our findings suggest that elevated levels of sCD14, GDF-15, and NT-proBNP among PLWH compared to PLWOH observed in the current cART era may only minimally reflect HIV-associated elevations in LAVI and ECV. Future studies of excess risk of myocardial disease among contemporary cohorts of PLWH should investigate mechanisms other than those connoted by the studied biomarkers.

Increased left atrial volume index is associated with more cardiovascular events in patients with acute coronary syndrome: HIJ-PROPER study findings.

AIM: To investigate the association between the left atrial volume index (LAVI) and the incidence of cardiovascular events in patients with acute coronary syndrome (ACS) who did not have atrial fibrillation (AF). METHODS: In this sub-analysis of the HIJ-PROPER study, 226 ACS patients who did not have a history of AF were enrolled. Participants were divided into two groups according to the LAVI cut-off level calculated by receiver operating characteristic (ROC) curve analysis to predict the primary endpoint, and cardiovascular events were compared between groups. The primary endpoint was the first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure. RESULTS: ROC curve analysis for the occurrence of composite of cardiovascular events indicated a LAVI cut-off point of 34 mL/m2 . Based on this, 131 patients (58.0%) were in the LAVI < 34 mL/m2 group and 95 (42.0%) were in the LAVI ≥ 34 mL/m2 group. Over a median follow-up period of 4.0 years [interquartile range: 3.2, 5.1], cardiovascular events were noted in 7 and 15 patients in the LAVI < 34 mL/m2 and LAVI ≥ 34 mL/m2 groups, corresponding to an incidence rate of 5.3% and 15.8%, respectively. Patients with a LAVI value ≥ 34 mL/m2 had a significantly higher risk of cardiovascular events than those with a LAVI value < 34 mL/m2 (hazard ratio: 2.93; 95% confidence interval: 1.19-7.22; P = .014). The tendency was similar after adjusting for several confounders (P = .025). CONCLUSION: In ACS patients without AF, elevated LAVI was associated with increased cardiovascular events. CLINICAL TRIAL REGISTRATION: International standard randomized controlled trial (URL: https://www.umin.ac.jp; UMIN000002742).

Phosphodiesterase inhibitor for heart failure with preserved ejection fraction: A systematic review and meta-analysis.

Background: Although heart failure with preserved ejection fraction (HFpEF) is a serious disease, only limited options are available for its treatment. Recent studies have analyzed the effects of phosphodiesterase (PDE) inhibitors, especially PDE5 and PDE3 inhibitors, in patients with HFpEF, with mixed outcomes. Methods: We searched PUBMED and EMBASE databases up to August 2021. Randomized controlled trials (RCTs) and clinical trials that tested the effects of PDE inhibitors on patients with HFpEF were included as eligible studies. Indicators of left ventricular (LV) function, pulmonary arterial pressure (PAP), right ventricular (RV) function, exercise capacity, and quality of life (QOL) were used to evaluate the efficacy of PDE inhibitors in HFpEF. Results: Six RCTs that reported in 7 studies were included to evaluate the efficiency of PDE inhibitors on HFpEF patients. In the pooled analysis, PDE inhibitors showed insignificant changes in the ratio of early diastolic mitral inflow to annular velocities, left atrial volume index, pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), peak oxygen uptake, 6-minute walking test distance, as well as Kansas City Cardiomyopathy Questionnaire score. However, substantial improvement was observed in the tricuspid annular plane systolic excursion (TAPSE). Additionally, the regression analysis showed that PDE inhibitor administration time is a critical factor for the decrease in PASP. Conclusions: PDE inhibitors did not effectively improve LV function, PAP, exercise capacity, and QOL in patients with HFpEF. However, they improved RV function with significant difference, suggesting that PDE inhibitors might be a promising option for HFpEF patients with RV dysfunction.

Recurrence of atrial fibrillation after pulmonary vein isolation in dependence of arterial stiffness.

BACKGROUND: Arterial stiffness (AS) has emerged as a strong predictor of cardiovascular (CV) diseases. Although increased AS has been described as a predictor of atrial fibrillation (AF), its role as a risk marker for AF recurrence has not yet been elucidated. METHODS: Patients with AF who underwent pulmonary vein isolation (PVI) were included in this study. Presence of AS was evaluated by measuring aortic distensibility (AD) of the descending aorta by transoesophageal echocardiography. RESULTS: In total, 151 patients (mean ± standard deviation (SD) age 71.9 ± 9.8 years) were enrolled and followed for a median duration of 21 months (interquartile range 15.0-31.0). During follow-up, AF recurred in 94 (62.3%) patients. AF recurrence was seen more frequently in patients with permanent AF (27% vs 46%, p = 0.03) and in those who had undergone prior PVI (9% vs 23%, p = 0.02). AD was significantly reduced in patients with AF recurrence (mean ± SD 2.6 ± 2.3 vs 1.5 ± 0.7â€¯× 10-3 mm Hg-1, p < 0.0001), as well as left atrial volume index (LAVI) (mean ± SD 29 ± 12 vs 44 ± 15 ml/m2, p < 0.0001). Multivariable analysis revealed LAVI (odds ratio (OR) 2.9, 95% confidence interval (CI) 1.2-3.4) and AS (OR 3.6, 95% CI 2.8-4.1) as independent risk factors of AF recurrence. CONCLUSION: Increased AS and left atrial size were independent predictors of AF recurrence after PVI. AD as surrogate marker of AS seemed to reflect the overall CV risk. In addition, AD was significantly correlated with left atrial size, which suggests that increased AS leads to atrial remodelling and thus to AF recurrence. TRIAL REGISTRATION: German registry for clinical studies (DRKS), DRKS00019007.

Ablation outcomes for atypical atrial flutter versus recurrent atrial fibrillation following index pulmonary vein isolation.

BACKGROUND: Data related to electrophysiologic characteristics of atypical atrial flutter (AFL) following atrial fibrillation (AF) ablation and its prognostic value on repeat ablation success are limited. METHODS: We studied consecutive patients who underwent a repeat left atrial (LA) ablation procedure for either recurrent AF or atypical AFL, at least 3 months after index AF ablation, between January 2012 and July 2019. The demographics, clinical history, procedural data, complications, and 1-year arrhythmia-free survival rates were recorded for each subject after the first repeat ablation. RESULTS: A total of 336 patients were included in our study. Among these 336 patients, 102 underwent a repeat ablation procedure for atypical AFL and 234 underwent a repeat ablation procedure for recurrent AF. The mean age was 63.7 ± 10.7 years, and 72.6% of patients were men. The atypical AFL cohort had significantly higher LA diameters (4.6 vs. 4.4 cm, p = .04) and LA volume indices (LAVi; 85.1 vs. 75.4 ml/m2 , p = .03) compared to AF patients at repeat ablation. Atypical AFL patients were more likely to have had index radiofrequency (RF) ablation (as opposed to cryoballoon) than recurrent AF patients (98% vs. 81%, p = .01). Atypical AFLs were roof-dependent in 35.6% and peri-mitral in 23.8% of cases. Major complications at repeat ablation occurred in 0.9% of the total cohort. Arrhythmia-free survival at one year was significantly higher in the recurrent atypical AFL compared to the recurrent AF cohort (75.5 vs. 65.0%, p = .04). CONCLUSION: In our series, roof-dependent flutter is the most common form of atypical atrial flutter post AF ablation. Patients developing atypical AFL after index AF ablation have greater LA dimensions than patients with recurrent AF. The success rate of first repeat ablation is significantly higher among patients with recurrent atypical AFL as compared to recurrent AF after index AF ablation.