Independent Predictor Of Heart Failure Research Articles

Fibroblast growth factor 23 independently predicts adverse outcomes after an acute coronary syndrome.

Abnormalities of mineral metabolism (MM) have been related to cardiovascular disorders. There are no reports on the prognostic role of MM after an acute coronary syndrome (ACS). We aim to assess the prognostic role of MM after an ACS. Plasma levels of components of MM [fibroblast growth factor 23 (FGF23), calcidiol, parathormone, klotho, and phosphate], high-sensitivity C-reactive protein, and N-terminal-pro-brain natriuretic peptide were measured in 1190 patients at discharge from an ACS. The primary outcome was a combination of acute ischaemic events, heart failure (HF) and death. Secondary outcomes were the separate components of the primary outcome. Age was 61.7±12.2years, and 77.1% were men. Median follow-up was 5.44 (3.03-7.46) years. Two hundred and ninety-four patients developed the primary outcome. At multivariable analysis FGF23 (hazard ratio, HR 1.18 [1.08-1.29], P<0.001), calcidiol (HR 0.86 [0.74-1.00], P=0.046), previous coronary or cerebrovascular disease, and hypertension were independent predictors of the primary outcome. The predictive power of FGF23 was homogeneous across different subgroups of population. FGF23 (HR 1.45 [1.28-1.65], P<0.001) and parathormone (HR 1.06 1.01-1.12]; P=0.032) resulted as independent predictors of HF. FGF23 (HR 1.21 [1.07-1.37], P=0.002) and calcidiol (HR 0.72 [0.54-0.97), P=0.028) were independent predictors of death. No biomarker predicted acute ischaemic events. FGF23 predicted independently the primary outcome in patients with estimated glomerular filtration rate>60mL/min/1.73m2 . FGF23 and other components of MM are independent predictors of HF and death after an ACS. This effect is homogeneous across different subgroups of population, and it is not limited to patients with chronic kidney disease.

Clinical utility and prognostic value of right atrial function in severe tricuspid regurgitation. One more piece of the puzzle

Abstract Background Optimal management of severe tricuspid regurgitation (TR) remains controversial. While right ventricular systolic function is an established prognostic marker of outcomes, the potential role of right atrial (RA) function is unknown. Purpose This study aimed to describe RA function by 2D speckle tracking echocardiography (STE) in at least severe TR and to evaluate its potential association with cardiovascular outcomes. Methods Consecutive patients with at least (≥) severe TR (severe, massive or torrential TR) evaluated in the Heart Valve Clinic following a comprehensive clinical protocol were included. Consecutive control subjects and patients with permanent isolated AF were included for comparison (control and AF group respectively). RA function was measured with 2D-STE and RA reservoir strain (RASr) was calculated in all subjects (figure 1, AutoStrain, Philips Medical Systems the EPIQ system). The interobserver variability of RA strain was assessed in 30 randomly selected subjects (20 TR+5 AF+5 controls). A combined endpoint of hospital admission due to heart failure (HF) or all cause mortality was defined. Results A total of 227 patients with severe TR, 20 AF patients and 20 controls subjects were included in this study. Patients with at least severe TR showed lower RASr compared to controls and to AF patients (p&amp;lt;0,05). After a median follow-up of 26 months (IQR: 15-48 months), n=83 patients with severe TR (37%) reached the combined endpoint. Patients with events showed lower values of RASr (p&amp;lt;0,01 for both). RASr was an independent predictor of heart failure and all cause mortality adjusted by additional imaging prognostic parameters in a multivariable analysis (biplane vena contracta, RV end-diastolic area, and RV- free wall longitudinal strain [LR Chi2 : 49,7, p&amp;lt;0,001]). RA area or volume was not associated with outcomes. A cut-off value of RASr of &amp;lt;10% held the best accuracy to predict outcomes (adjusted HR 3,8 (2,4-6,1), p&amp;lt;0,001, figure 2). Inter-observer agreements for RA strain values across the whole cohort were high (intraclass correlation coefficient for RASr, RAScd and RASct, r= 0,95, r=0,86, r=0,92 respectively). Conclusions Evaluation of RA function by 2D-STE is feasible, reproducible and is an independent predictor of heart failure and all-cause mortality in patients with at least severe TR.LA STRAINKaplan Meier Curves

Accelerated decline in lung function is associated with cardiac structure and function and independently predicts incident heart failure

Abstract Background The association between impaired lung function and cardiovascular disease is well known. However, it is not fully understood how a decline in lung function affects the development of cardiovascular disease including heart failure (HF). Purpose We aimed to investigate the association between declining lung function and changes in cardiac structure and function. Furthermore, we investigated the association between a decline in lung function and the risk of HF. Methods The study included 2,995 participants from a general population study. All participants had two examinations with spirometry performed 10 years apart. Participants were free of valvular heart disease and HF. A subsample (n=1,164) was also examined with echocardiography at both timepoints. The decline in the forced expiratory volume in one second (dFEV1) from the first visit to the second visit, was calculated. The change in cardiac structure and function between the two visits, was calculated as the decline in left ventricular ejection fraction (dLVEF), global longitudinal strain (dGLS), left ventricular mass index (dLVMi) and the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (dE/e’). Linear regression models were adjusted for the baseline FEV1 and echocardiographic value to account for regression to the mean. Outcome was incident HF. Results The entire sample consisted of 57% women, and the mean age was 62 ± 14 years. A total of 59% had hypertension, 8% had ischemic heart disease (IHD), 6% had diabetes, and 18% were active smokers. Mean FEV1 at baseline was 2.8 ± 0.95 liters (95 ± 19% as percentage of the predicted value). The mean decline in FEV1 between visits (median 10.8 years, IQR: 10.3-11.2) was 309 ± 362 mL. In the subsample examined with echocardiography, decreasing dLVEF was significantly associated with decreasing dFEV1 (p=0.030) in multivariable linear regression analysis, whereas dGLS, dLVMi, and dE/e’ were not. In the total study sample, 105 participants developed incident heart failure following the second visit during a median follow-up of 5.4 years (IQR: 4.5-6.3). Participants in the lowest quartile of dFEV1 (no change or increase) had an incidence rate of 2.48 per 1,000 person years (95%CI 1.33-4.60) versus participants in the highest quartile of dFEV1 (largest decline) with an incidence rate of 13.9 per 1,000 person years (95%CI 10.6-18.3), p&amp;lt;0.001. In multivariable Cox regression analysis, dFEV1 was an independent predictor of HF with a hazard ratio of 3.37 per 1 liter decline (95%CI 1.53-7.43, p=0.003). Conclusion We found a strong association between a decline in FEV1 and a decline in LVEF over a decade. Decreasing FEV1 was independently associated with incident HF. The incidence was highest for those with the largest decline in FEV1.A) Linear association B) Hist. of dLVEFA) Incidence rate B) Cumulative inc.

Ai-based fully automated left atrioventricular coupling index as a prognostic marker in patients undergoing stress-CMR

Abstract Background The left atrioventricular coupling index (LACI) is a strong and independent predictor of heart failure (HF) in individuals without clinical cardiovascular disease. Its prognostic value is not established in patients with cardiovascular disease. Purpose To determine in patients undergoing stress CMR whether fully automated artificial intelligence-based LACI can provide incremental prognostic value to predict HF. Methods Between 2016 and 2018, we conducted a longitudinal study including all consecutive patients with abnormal (inducible ischemia or late gadolinium enhancement (LGE)) vasodilator stress CMR. Control subjects with normal stress CMR were selected using propensity score-matching. LACI was defined as the ratio of LA to LV end-diastolic volumes. The primary outcome included hospitalization for acute HF or cardiovascular death. Cox regression was used to evaluate the association of LACI with the primary outcome after adjustment for traditional risk factors. Results In 2,134 patients [65±12 years, 77% men, 1:1 matched patients (1,067 with normal and 1,067 with abnormal CMR)], LACI was positively associated with the primary outcome (median follow-up 5.2 (4.8-5.5) years) before and after adjustment for risk factors in the overall propensity-matched population (adjusted hazard ratio [HR], 1.18 [95%CI, 1.13-1.24] per 0.1% increment), patients with abnormal (adjusted HR, 1.22 [95%CI, 1.14-1.30] per 0.1% increment), and normal CMR (adjusted HR, 1.12 [95%CI, 1.05-1.20] per 0.1% increment; all p&amp;lt;0.001). After adjustment, a higher LACI of ≥25% showed the greatest improvement in model discrimination and reclassification over and above traditional risk factors and stress CMR findings (C-statistic improvement: 0.16; NRI=0.388; IDI=0.153, all p&amp;lt;0.001; LR-test p&amp;lt;0.001). Conclusion LACI is independently associated with hospitalization for HF and cardiovascular death in patients undergoing stress CMR, with an incremental prognostic value over traditional risk factors including inducible ischemia and LGE.LACI measurement method using CMRKaplan-Meier curves by LACI value

Joint Association of Albuminuria and Left Ventricular Hypertrophy With Incident Heart Failure in Adults at High Risk With Hypertension: A Systolic Blood Pressure Intervention Trial Substudy

Albuminuria and left ventricular hypertrophy (LVH) are independent predictors of heart failure (HF); however, to the best of our knowledge, their combined effect on the risk of HF has not yet been explored. Therefore, we examined the joint associations of albuminuria and electrocardiographic-LVH with incident acute decompensated HF (ADHF), and whether albuminuria/LVH combinations modified the effects of blood pressure control strategy in reducing the risk of ADHF. A total of 8,511 participants from the Systolic Blood Pressure Intervention Trial (SPRINT) were included. Electrocardiographic-LVH was present if any of the following criteria were present: Cornell voltage, Cornell voltage product, or Sokolow-Lyon. Albuminuria was defined as urine albumin/creatinine ratio ≥30mg/g. ADHF was defined as hospitalization or emergency department visit for ADHF. Cox proportional hazard models were used to examine the association of neither LVH nor albuminuria (reference), either LVH or albuminuria, and both (LVH+albuminuria) with incident ADHF. Over a median follow-up of 3.2years, 182 cases of ADHF occurred. In adjusted models, concomitant albuminuria and LVH were associated with greater risk of ADHF than either albuminuria or LVH in isolation (hazard ratio [95% confidence interval]: 4.95 [3.22 to 7.62], 2.04 [1.39 to 3.00], and 1.47 [0.93 to 2.32], respectively, additive interaction p=0.01). The effect of intensive blood pressure in reducing ADHF was attenuated in participants with coexisting albuminuria and LVH without any interaction between treatment group assignment and albuminuria/LVH categories (interaction p=0.26). In conclusion, albuminuria and LVH are additive predictors of ADHF. The effect of intensive blood pressure control in reducing ADHF risk did not vary significantly across albuminuria/LVH combinations.

The association between erector spinae muscle content and chronic heart failure and its severity.

Previous studies have shown a significant reduction in skeletal muscle content in patients with chronic heart failure (CHF). The present study focused on the erector spinae muscle (ESM) to determine whether ESM content is associated with the development and severity of CHF. A total of 652 patients were included in this trial for the study. According to the diagnostic criteria of CHF, 652 patients were divided into two groups, namely, the control group (268 patients) and the CHF group (384 patients). Meanwhile, to assess whether the ESM is associated with the severity of CHF, patients in the CHF group were divided into two groups according to left ventricular ejection fraction (LVEF) values: heart failure with preserved ejection fraction (HFpEF, LVEF ≥50%, 256 patients) and heart failure with reduced ejection fraction (HFrEF, LVEF ≤40%, 68 patients). Receiver operating curve analysis was performed to assess whether ESM content could predict CHF and determine its severity. Compared with the control group, the patients in the CHF group were older, the prevalence of coronary heart disease (CHD) and atrial fibrillation was higher, the colour ultrasound results showed that LVEF decreased significantly, and the left ventricular end-diastolic internal diameter and left ventricular end-systolic internal diameter increased significantly. Besides, patients in the CHF group had significantly lower ESM content, and ESM is an independent predictor of heart failure, with an odds ratio of 0.713 (CHF group vs. control group, 95% confidence interval 0.626-0.811, P<0.001). Compared with the HFpEF group, the HFrEF group has a lower prevalence of CHD, LVEF decreased significantly, the left ventricular end-diastolic internal diameter and left ventricular end-systolic internal diameter increased significantly, also patients in the HFrEF group had significantly lower ESM content compared with patients in the HFpEF group, and ESM is an independent predictor of the severity of heart failure, with an odds ratio of 0.514 (HFrEF group vs. HFpEF group, 95% confidence interval (0.418-0.633, P<0.05). The results of receiver operating curve analysis showed that the sensitivity and specificity of ESM content for the diagnosis of CHF were 65.6% and 71.6%, respectively, while the sensitivity and specificity of ESM content for predicting the severity of CHF were 47.1% and 89.1%, respectively. The ESM is of great value in predicting the onset and severity of CHF.

Development and validation of a prediction model based on machine learning algorithms for predicting the risk of heart failure in middle-aged and older US people with prediabetes or diabetes.

The purpose of this study was to develop and validate a machine learning (ML) based prediction model for the risk of heart failure (HF) in patients with prediabetes or diabetes. We used 3527 subjects aged 40 years and older with a prior diagnosis of prediabetes or diabetes from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. The search for independent risk variables linked to HF was conducted using univariate and multivariable logistic regression analysis. The 3527 subjects were randomly divided into training set and validation set in a 7:3 ratio. Five ML models were built on the training set using five ML algorithms, including random forest (RF), and then validated on the validation set. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis and Bootstrap resampling method were used to measure the predictive performance of the five ML models. Multivariate logistic regression analysis showed that age, poverty-to-income ratio, myocardial infarction condition, coronary heart disease condition, chest pain condition, and glucose-lowering medication use were independent predictors of HF. By comparing the performance of the five ML models, the RF model (AUC = 0.978) was the best prediction model. The risk of HF in middle-aged and elderly patients with prediabetes or diabetes can be accurately predicted using ML models. The best prediction performance is presented by RF model, which can assist doctors in making clinical decisions.

AI-based fully automated left atrioventricular coupling index as a prognostic marker in patients undergoing stress-CMR

The left atrioventricular coupling index (LACI) is a strong and independent predictor of heart failure (HF) in individuals without clinical cardiovascular disease. To determine in patients undergoing stress CMR whether fully automated artificial intelligence-based LACI can provide incremental prognostic value to predict HF. Between 2016 and 2018, we conducted a study including all consecutive patients with abnormal vasodilator stress CMR [inducible ischemia or late gadolinium enhancement (LGE)]. Control subjects with normal CMR were selected using propensity score-matching. LACI was defined as the ratio of LA to LV end-diastolic volumes. The primary outcome included hospitalization for acute HF or cardiovascular death using Cox regression. In 2662 patients [65 ± 12 years, 68% men, 1:1 matched patients (1331 with normal and 1331 with abnormal CMR)], LACI was positively associated with the primary outcome [median follow-up 5.2 (4.8–5.5) years] before and after adjustment for risk factors in the overall propensity-matched population [adjusted hazard ratio (HR), 5.94 (95%CI, 3.74–9.45) per 0.1% increment], patients with abnormal [adjusted HR, 6.38 (95%CI, 3.77–10.8) per 0.1% increment], and normal CMR [adjusted HR, 6.15 (95%CI, 2.97–12.7) per 0.1% increment; all P < 0.001]. After adjustment, a higher LACI of ≥ 25% showed the greatest improvement in model discrimination and reclassification over and above traditional risk factors and stress CMR findings (C-statistic improvement: 0.15; NRI = 0.705; IDI = 0.398, all P < 0.001; LR-test P < 0.001). LACI is independently associated with hospitalization for HF and cardiovascular death in patients undergoing stress CMR, with an incremental prognostic value over traditional risk factors including inducible ischemia and LGE (Fig. 1).

Predicting heart failure during hospitalization in myocarditis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Currently, there is little evidence available regarding their predictive potential of Monocyte-to-lymphocyte ratio (MLR) in patients diagnosed with myocarditis. Purpose We aimed to investigate if MLR can predict heart failure during hospitalization in patients with clinical suspicious of acute myocarditis. Methods Retrospective study with patients admitted with the clinical suspicion of myocarditis in our center from February/2016 to September/2021. A total of 74 patients were included and divided into two groups based on MLR. ROC-analysis was conducted and AUC was calculated for the prediction of heart failure during hospitalization (0.82). Optimal cut-off for MLR was calculated by means of the Youden Index (MLR ≥ 0,817 (sens.: 73%, spec.: 80%). The primary outcome was heart failure during hospitalization. Results We included 74 patients (90,5% males; mean age 37,1±15,1 years old), 96,8% presenting with chest pain and 68,9% presenting with ST-segment elevation on electrocardiogram. During hospitalization, 4 patients needed ionotropic support, 7 had supraventricular tachycardia, 14 non-sustained ventricular tachycardia, 2 sustained ventricular tachycardia, 1 needed extracorporeal membrane oxygenation and 11 had heart failure. Both groups had similar age (39,0±16,9 vs 36,5±16,7 years, p=0,59), previous history of myocarditis (8,9% vs 5,6%, p=0,65), smoking history (16,7% vs 33,9%, p=0,34), diabetes mellitus (7,1% vs 2,6%, p=0,24), dyslipidemia (33,3% vs 19,6%,p=0,23), arterial hypertension (11,1% vs 14,3%,p=0,73), ST-segment elevation on admission (72,7% vs 63,8%, p=0,45), pro-BNP levels on admission [522 (IQR 222-1253) mg/dl vs 495 (IQR 222-970) mg/dl, p = 0,46]. Patients with MLR ≥ 0,817 (24,3%) had lower Left ventricular ejection fraction on admission (45,9%±14,1% vs 53,3%±8,4, p=0,008), high Peak C-reactive protein [13 (IQR 4,5-22) vs 4,5 (IQR 4-6,1), p=0,001] and peak troponin levels [1,98 (IQR 0,98-2,81) vs 0,87 (IQR 0,55-1,74), p=0,007] were higher in this group. Throughout a median hospital stay of 4 days (IQR 3,5–7), 11 patients (17,7%) experienced the primary outcome. After adjusting for possible cofounders, MLR ≥ 0,817 was an independent predictor of heart failure during hospitalization (HR 6,83, 95% CI 1,55-30,01, p=0,011). Conclusion MLR in our population, was a predictive factor for heart failure during hospitalization in patients with acute myocarditis. MLR could facilitate an early risk stratification and clinical management in these patients.

Higher peripheral thyroid sensitivity is linked to a lower risk of heart failure after acute myocardial infarction.

It is still not clear how free triiodothyronine (FT3) to free thyroxine (FT4) ratio affects the prognosis of acute myocardial infarction (AMI), especially the risk of heart failure (HF) subsequent AMI. The purpose of this study was to see how peripheral sensitivity to thyroid hormones, as measured by the FT3/FT4 ratio, affected HF and mortality after AMI. Our study was a retrospective cohort study. The primary endpoint was HF post-AMI during and after hospitalization. The secondary endpoints were all-cause death and cardiovascular death after hospitalization. The main sample included 3,648 AMI inpatients with a median age of 61.0 years, and 68.9% were male. In the fully adjusted model, compared with patients in the lowest Q1 of the FT3/FT4 ratio, the risk of in-hospital HF was reduced by 44% (OR 0.56, 95% CI 0.44-0.72, P trend < 0.001), the risk of out-of-hospital HF in the highest Q4 patients was reduced by 37% (HR 0.63, 95% CI 0.48-0.84, P trend = 0.001), and the risks of all-cause and cardiovascular death were also significantly reduced. The analysis of different subgroups is consistent with the overall results. Furthermore, the sensitivity analysis of the euthyroid sample of 2,484 patients was consistent with the main sample. Mediation analysis showed that altered levels of NT-proBNP were mediators between the FT3/FT4 ratio and all endpoints in our study. The thyroid hormone peripheral sensitivity of the FT3/FT4 ratio is an independent predictor of heart failure and mortality after AMI.

AI-Based Fully Automated Left Atrioventricular Coupling Index as a Prognostic Marker in Patients Undergoing Stress CMR

BackgroundThe left atrioventricular coupling index (LACI) is a strong and independent predictor of heart failure (HF) in individuals without clinical cardiovascular disease. Its prognostic value is not established in patients with cardiovascular disease. ObjectivesThis study sought to determine in patients undergoing stress cardiac magnetic resonance (CMR) whether fully automated artificial intelligence–based LACI can provide incremental prognostic value to predict HF. MethodsBetween 2016 and 2018, the authors conducted a longitudinal study including all consecutive patients with abnormal (inducible ischemia or late gadolinium enhancement) vasodilator stress CMR. Control subjects with normal stress CMR were selected using propensity score matching. LACI was defined as the ratio of left atrial to left ventricular end-diastolic volumes. The primary outcome included hospitalization for acute HF or cardiovascular death. Cox regression was used to evaluate the association of LACI with the primary outcome after adjustment for traditional risk factors. ResultsIn 2,134 patients (65 ± 12 years, 77% men, 1:1 matched patients [1,067 with normal and 1,067 with abnormal CMR]), LACI was positively associated with the primary outcome (median follow-up: 5.2 years [IQR: 4.8-5.5 years]) before and after adjustment for risk factors in the overall propensity-matched population (adjusted HR: 1.18 [95% CI: 1.13-1.24]), in patients with abnormal CMR (adjusted HR per 0.1% increment: 1.22 [95% CI: 1.14-1.30]), and in patients with normal CMR (adjusted HR per 0.1% increment: 1.12 [95% CI: 1.05-1.20]) (all P < 0.001). After adjustment, a higher LACI of ≥25% showed the greatest improvement in model discrimination and reclassification over and above traditional risk factors and stress CMR findings (C-index improvement: 0.16; net reclassification improvement = 0.388; integrative discrimination index = 0.153, all P < 0.001; likelihood ratio test P < 0.001). ConclusionsLACI is independently associated with hospitalization for HF and cardiovascular death in patients undergoing stress CMR, with an incremental prognostic value over traditional risk factors including inducible ischemia and late gadolinium enhancement.

Abstract P522: Breast Arterial Calcification Predicts Heart Failure Across Racial and Ethnic Groups

Introduction: Breast arterial calcification (BAC), which can be seen on mammograms, is emerging as a risk stratification tool for cardiovascular disease (CVD) outcomes including heart failure, though how prediction varies by race and ethnicity is unknown. Methods: This single-center, retrospective study included 18,092 women age ≥40 years who had a digital mammogram between 2008-2016 and clinical follow-up through 2019. BAC was quantified using an automated algorithm (CureMetrix), resulting in a continuous Bradley score. Heart failure (HF) events and self-reported race and ethnicity were obtained via medical records. Adjusted hazard ratios (aHR) were calculated using Cox proportional hazard regression models with interaction terms to evaluate the effect of race and ethnicity on the association between BAC (presence/absence; or Bradley score quartile among those with BAC) with incident HF, adjusted for age, diabetes, smoking, systolic and diastolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and history of CVD and chronic kidney disease. Results: Mean age was 57±11 years with 11,319 (63%) of women White, 907 (5%) Black, 1,694 (9%) Hispanic, 2,321 (13%) Asian, and 1,851 (10%) Other. Over a median follow-up of 3.0 years, 149 of the 4,076 women with BAC (3.7%) developed HF compared to 149 of the 14,016 women without BAC (1.1%). Presence of BAC was associated with incident HF (aHR 1.38, 95% CI 1.21-1.58, p&lt;0.001) overall and among all racial and ethnic groups, with increased risk seen for increasing quartiles of Bradley score (aHR 1.17 in the first, 1.30 in the second, 1.79 in the third, 1.69 in the fourth; p-trend&lt;0.001). The presence of BAC was an even stronger predictor of HF in Black women compared to White women ( Figure ; aHR 1.51 [1.00-2.30], p interaction=0.05). Conclusions: The presence and degree of BAC on a mammogram is an independent predictor of HF and may serve as an especially strong risk factor among Black women.

142 ADVANCED HEART FAILURE IN PATIENTS WITH ARRHYTHMOGENIC CARDIOMYOPATHY

Abstract Background Arrhythmogenic Cardiomyopathy (ACM) is a primary disease of the heart muscle, characterized by fibro-fatty myocardial replacement. Improvements in the clinical diagnosis and antiarrhythmic therapy, including the use of the defibrillator (ICD) and endo-epicardial catheter ablation, have increased the survival of these patients, who experience late complications such as advanced heart failure, which sometimes requires cardiac transplantation. Aim of the study To evaluate clinical, instrumental and genetic features of patients affected with ACM who developed heart failure (HF) and to sought for possible predictive factors of HF. Methods From the entire cohort of probands and family members followed at the Cardiomyopathy unit of our University (555 patients), 34 patients (29%), both probands (n= 26, 77%) and family members who experienced HF (6%) were selected (24 males, 71%). Their anamnestic, clinical, and instrumental data were compared with those without episodes of HF (n-HF). Results The mean age at diagnosis in HF cohort was 45.2 (±18) years. In 14 patients (41%) HF was the first symptom that led to diagnosis. According to 2010 TFC 30 patients (88%) had a definite diagnosis of ACM. The most frequently observed phenotype was the biventricular ACM (n=27, 79%). A disease-related genetic variant was found in 18 (53%) and DSP was the more common disease-gene, accounting for 24% of cases. The mean duration of follow-up was 12.6 (±11.0) years (min-max, 1-20 years). During this period a total of 14 subjects (41.2%) experienced life-threatening arrhythmias (LTA), while 13 patients (38.2%) died, of whom 11 (84.6%) because of refractory HF. Eighteen patients (53%) underwent cardiac transplantation (mean age 43±17 years), approximately 4 (±3.5) years after the onset of symptoms. Comparison with the n-HF cohort of ACM patients showed a significant difference on presence of T-wave inversion (TWI) in V1-V3 (p=0.001), TWI in V4-V6 (p=0.010), low QRS voltages both in precordial and limb leads (both p&amp;lt;0.001) and presence of left bundle-branch block and right bundle-branch block (both p&amp;lt;0.001). Regarding CMR, HF cohort was characterized by a significantly more dilated right and left ventricle EDV (both p&amp;lt;0.001), EF reduction (both p&amp;lt;0.001), presence of wall motion alterations (respectively, p=0.007 and p&amp;lt;0.001) and LGE (respectively, p=0.002 and p=0.005) compared to n-HF group. Regarding outcomes evaluation, the HF group showed more frequently LTA (HF=41.2% vs n-HF 21.5%, p=0.008). Finally, the presence of right bundle-branch block at ECG (OR=20.562, CI 1.884-224.413, p=0.013) and of impaired RV ejection fraction (OR=0.821, CI 0.719-0.937, p=0.004) were found to be independent predictors of HF. Conclusions Heart failure is a rare complication in patients affected with ACM, with a prevalence of 6% in our study. The mean age of onset of HF was 45.2 (±18) years. Furthermore, 18 patients (53%) had an unfavorable progression to heart transplantation. The presence of right bundle branch block at ECG and an impaired CMR RV-EF were found to be predictors of HF. Our results suggest the importance of scheduling a close follow-up in ACM patients who show initial signs and/or symptoms of HF, taking into consideration the fast rate of progression to refractory HF, once established.

Predictors of heart failure in children with congenital heart disease

Background Heart failure continues to be a significant contributor to morbidity and mortality in children with congenital heart disease (CHD). Little is known about heart failure in children. Identifying predictors of heart failure in children with CHD can serve to guide preventive strategies to heart failure.&#x0D; Objective To understand the predictors of heart failure of children with congenital heart disease.&#x0D; Methods A nested, case-control study was performed using secondary data based on a prospective study previously conducted in Dr Sardjito Tertiary Hospital in Yogyakarta in years 2011-2013. We included children aged 1 month-18 years who had been diagnosed with CHD by echocardiography. Age, sex, type of CHD, CHD complexity, as well as presence of syndrome, no pulmonary obstruction, pneumonia, and malnutrition were analyzed as potential predictors of heart failure. Results are presented as odds ratios (OR) with 95% confidence intervals (95%CI).&#x0D; Results A total of 2,646 children were hospitalized in Dr Sardjito Tertiary Hospital during the study period. Congenital heart disease was noted in 216 children (8.16%), 200 (7.5%) of whom met the inclusion criteria. The 100 children with heart failure had median age of 1.5 years and 15% died during hospitalization. Multivariate analysis revealed that acyanotic CHD (OR 2.69; 95%CI 1.45 to 5.00), no pulmonary obstruction (OR 3.05; 95%CI 1.33 to 6.99) and the presence of pneumonia (OR 2.04; 95%CI 1.03 to 4.06) were statistically significant as independent predictors of heart failure in children with CHD. However, sex, age, CHD complexity, as well as presence of a syndrome, and malnutrition were not significantly associated with heart failure in children with CHD.&#x0D; Conclusion The predictors of heart failure in children with CHD were acyanotic CHD, no pulmonary obstruction, and presence of pneumonia.

Prognostic value of a left atrioventricular coupling index in pre- and post-menopausal women from the Multi-Ethnic Study of Atherosclerosis.

Sex hormones associated with both the left atrial (LA) and left ventricular (LV) structures in women, but the association of menopause status with left atrioventricular coupling is not established. To assess the prognostic value of a left atrioventricular coupling index (LACI) in peri-menopausal women without a history of cardiovascular disease (CVD). In all women participating in MESA study with baseline cardiovascular MRI, the LACI was measured as the ratio of the LA end-diastolic volume to the LV end-diastolic volume. Cox models were used to assess the association between the LACI and the outcomes of atrial fibrillation (AF), heart failure (HF), coronary heart disease (CHD) death, and hard CVD. Among the 2,087 women participants (61 ± 10 years), 485 cardiovascular events occurred (mean follow-up: 13.2 ± 3.3 years). A higher LACI was independently associated with AF (HR 1.70; 95%CI [1.51-1.90]), HF (HR 1.62; [1.33-1.97]), CHD death (HR 1.36; [1.10-1.68]), and hard CVD (HR 1.30; [1.13-1.51], all p < 0.001). Adjusted models with the LACI showed significant improvement in model discrimination and reclassification when compared to traditional models to predict: incident AF (C-statistic: 0.82 vs. 0.79; NRI = 0.325; IDI = 0.036), HF (C-statistic: 0.84 vs. 0.81; NRI = 0.571; IDI = 0.023), CHD death (C-statistic: 0.87 vs. 0.85; NRI = 0.506; IDI = 0.012), hard CVD (C-statistic: 0.78 vs. 0.76; NRI = 0.229; IDI = 0.012). The prognostic value of the LACI had a better discrimination and reclassification than individual LA or LV parameters. In a multi-ethnic population of pre- and post-menopausal women, the LACI is an independent predictor of HF, AF, CHD death, and hard CVD. [https://clinicaltrials.gov/], identifier [NCT00005487].

Left atrial coupling index predicts heart failure and atrial fibrillation in the general population

Abstract Background It is well known that left atrial (LA) function and size can provide significant information regarding the risk of atrial fibrillation (AF) and heart failure (HF). The ratio of LA volume index and tissue doppler imaging a' (peak myocardial velocity of the left ventricle in late diastole exposing the atrial contraction) provides the LA volumetric/mechanical coupling index (LACi). LACI is a novel echocardiographic measurement which combines information of LA size and function in one measure with limited previous investigation. Purpose The aim of the present study was to investigate the prognostic value of LACi in relation to incident HF and AF in the general population. Methods The present study included 4,003 participants from a prospective general population. All participants were examined with echocardiography. Incident HF and AF were investigated as separate outcomes. Exclusion criteria were AF and/or HF at baseline. LACi was calculated as the index of LAVI (left atrial volume index) and peak tissue velocity at late diastole measured with pulsed wave Doppler at the septal base of the left ventricle. Results Mean age was 56±17 years, 57% were female, and median LACi was 2.3 [IQR: 1.8, 3.0]. The median follow-up time was 5.4 [IQR: 4.5, 6.3] years. A total of 82 and 164 developed HF and AF during follow-up, respectively. Median LACi was significantly higher among participants developing HF (2.6 [IQR: 2.1, 3.8], P&amp;lt;0.001) and AF (2.8 [IQR: 2.1, 4.1], P&amp;lt;0.001) compared to those who remained event free (2.3 [IQR: 1.8, 3.0]). Multivariable Cox proportional hazard regression models were constructed and adjusted for gender, age, smoking status, hypercholesterolemia, diabetes mellitus, ischaemic heart disease at baseline, hypertension, left ventricular ejection fraction and left ventricular diastolic function (E/e'). LACi was an independent predictor of incident HF and of AF in both univariable and multivariable Cox regression models (Figure 1). LACi remained a significant predictor of both HF and AF in a sensitivity analysis with subgroups in which LAVI was normal and enlarged, respectively (Figure 1). Conclusion LACi is an independent predictor of HF and AF in the general population. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): The Danish Heart Foundation and The Metropolitan Region of Denmark.

Clinical utility and prognostic value of right atrial function in severe tricuspid regurgitation. One more piece of the puzzle

Abstract Background Optimal management of severe tricuspid regurgitation (TR) remains controversial. While right ventricular systolic function is an established prognostic marker of outcomes, the potential role of right atrial (RA) function is unknown. Purpose This study was aimed to describe RA function by 2D speckle tracking echocardiography (STE) in severe TR and to evaluate its potential association with cardiovascular outcomes Methods Consecutive patients with at least severe TR (severe, massive or torrential TR) evaluated in the Heart Valve Clinic following a comprehensive clinical protocol were included. Consecutive control subjects and patients with permanent atrial fibrillation (AF) were included for comparison. RA function was measured with 2D-STE and 3 components of RA function were calculated: reservoir (RASr), conduit (RAScd) and contractile (RASct) RA values using an automatic 2D strain analytical software (AutoStrain, Philips Medical Systems the EPIQ system, Figure 1). A combined endpoint of hospital admission due to heart failure (HF) or all-cause mortality was defined. The interobserver variability of RA strain was assessed in 30 randomly selected subjects (20 TR+5 AF+5 controls). Results A total of 176 patients with severe TR, 20 AF patients and 20 controls subjects were included in this study. Patients with at least severe TR showed lower RASr and RAScd compared to controls and to AF patients (Figure 1 and Table 1, p&amp;lt;0.05). After a median follow-up of 28 months (IQR: 15–48 months), n=65 patients with severe TR (37%) reached the combined endpoint. 65 (37%) were admitted for right heart failure and 8% of the population (n=14) died. Patients with events showed lower values of RASr and RAScd (p&amp;lt;0.01 for both). Between both parameters RASr was more strongly associated with outcomes compared to RAScd (AUC 0.74 vs. 0.65, p&amp;lt;0.01). RASr was an independent predictor of heart failure and all cause mortality adjusted by additional imaging prognostic parameters in a multivariable analysis (biplane vena contracta, RV end-diastolic area, and RV-free wall longitudinal strain [LR χ2: 49.7, p&amp;lt;0.001]). RA area or volume was not associated with outcomes. A cut-off value of RASr of &amp;lt;9.4% held the best accuracy to predict outcomes (adjusted HR 3.2 (1.81–5.84), p&amp;lt;0.001, Figure 1). Inter-observer agreements for RA strain values across the whole cohort were high (intraclass correlation coefficient for RASr, RAScd and RASct, r=0.95, r=0.86, r=0,92 respectively) Conclusions Evaluation of RA function by 2D-STE is feasible, reproducible and is an independent predictor of heart failure and all-cause mortality in patients with at least severe TR. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): INSTITUTO CARLOS III

STREI: a new index of right heart function in isolated severe tricuspid regurgitation by Speckle tracking Echocardiography

Abstract Background Right ventricular (RV) performance is key in the management of patients with severe tricuspid regurgitation (TR); detection of RV dysfunction is crucial to identify on time patients that benefit from valve intervention. Conventional parameters of RV function by 2D echocardiography are influenced by changes on preload conditions and can remain unaffected until late stages of the disease. The right atrium (RA) has an important role in modulating RV filling and RA performance is impaired in severe TR. Potentially, an index that combines RV and RA function may reflect a broader view of the effects of severe TR in right heart function. Purpose 1) to evaluate the clinical utility of combining RV and RA strain for prediction of CV outcomes and 2) to design a novel index by Speckle-tracking echocardiography (STREI index) that integrates RA and RV information Methods Consecutive patients with at least severe TR (severe, massive or torrential TR) evaluated in the Heart Valve Clinic following a comprehensive clinical protocol were included. Consecutive control subjects and patients with permanent atrial fibrillation (AF) were included for comparison. Reservoir RA strain (RASr) and RV-free wall longitudinal strain (RV-FWLS) analysis were performed using novel, automated 2D strain analytical software (AutoStrain, Philips Medical Systems the EPIQ system, Figure 1). Novel STREI index was calculated with the formula: [2 × RV-FWLS] + RASr in absolute numbers. A combined endpoint of hospital admission due to heart failure (HF) or all-cause mortality was defined. The interobserver variability of RA strain was assessed in 30 randomly selected subjects (20 TR+5 AF+5 controls). Results A total of 176 patients with severe TR, 20 AF patients and 20 controls subjects were included in this study. Patients with TR showed lower STREI values compared to controls and to AF patients (TR vs. controls vs. AF: 55±18 vs. 116±12 vs. 70±13, p&amp;lt;0,001). After a median follow-up of 28 months (IQR: 15–48 months), n=65 patients with severe TR (37%) reached the combined endpoint. Patients with both abnormal strains (abnormal RV-FWLS and abnormal RASr strain) showed a significantly higher rate of events (Figure 2A). In a multivariable analysis, STREI index was an independent predictor of HF and mortality adjusted by vena contracta, RV end-diastolic area, NYHA class and BNP values (LR χ2: 46,1, p&amp;lt;0,001). A cut off value of STREI index &amp;lt;50% held the best accuracy to predict outcomes. An abnormal STREI index was associated with 6,1-fold increased risk of HF or death (HR 6,9 (3,9–12,3), p&amp;lt;0,001, Figure 2B) Inter-observer agreements for STREI values were high (intraclass correlation coefficient = 0,96). Conclusion STREI index is a feasible and reproducible new parameter of RV performance that independently predicts outcomes in patients with severe TR. Randomized studies should confirm its potential to identify those patients that benefit from earlier valve interventions. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto Carlos III

Prognostic impact of right ventricular strain in isolated severe tricuspid regurgitation

Abstract Background Right ventricular (RV) systolic function is determinant in the evaluation of patients with severe tricuspid regurgitation (TR). Timely detection of RV dysfunction with conventional 2D echocardiography is challenging. RV strain has emerged as an accurate and sensitive tool for evaluation of RV function with the capability of detecting subclinical RV dysfunction. Purpose This study was aimed to evaluate the prognostic value of RV strain parameters in consecutive stable patients with severe TR. Methods Consecutive patients in stable clinical status with at least severe TR (severe, massive or torrential TR) evaluated in the Heart Valve Clinic following a comprehensive clinical protocol were included. Patients with previous episodes of heart failure or scheduled for TV intervention were excluded. RV systolic function was measured with conventional echocardiographic indices (RV fractional area change [FAC], tricuspid annular plane systolic excursion [TAPSE], DTI S wave [`S]) and with Speckle-tracking echocardiography (STE) derived automatic peak global and free wall longitudinal strain (RV-GLS and RV-FWLS respectively) using the EPIQ system (Philips Medical Systems, Andover, Massachusetts). A combined endpoint of hospital admission due to heart failure (HF) or all-cause mortality was defined. The interobserver variability of RV strain was assessed in 20 randomly selected patients. Results A total of 176 patients were included in this study. Strain parameters detected higher percentage of RV dysfunction compared to conventional indices (figure 1). After a median follow-up of 28 months (IQR: 15–48 months), n=65 patients (37%) reached the combined endpoint. 65 (37%) were admitted for right heart failure and 8% of the population (n=14) died. Cumulative event-free survival was significantly worse in patients with impaired RV-GLS and RV-FWLS. Conventional indices of RV systolic function were not associated with outcomes (p&amp;gt;0.05 for all). In a multivariable analysis (in a model including NYHA class, BNP values, biplane VC, RV end-diastolic area, and RV-FWLS), RV-FWLS was an independent predictors of heart failure and CV mortality (figure 1 and 2; LR χ2: 40.2, p&amp;lt;0.001). Inter-observer agreements for RV strain values were high (intraclass correlation coefficient for RV-GLS and RV-FWLS, r=0.96 and r=0.98 respectively) Conclusion Clinical outcomes demonstrate that RV strain parameters are superior to conventional indices of RV function in patients with isolated ≥ severe TR and absence of previous episodes of heart failure. Among all parameters of RV function, RV-FWLS is the strongest independent predictor of mortality and HF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto Carlos III

Prognostic value of a left atrioventricular coupling index (LACI) in pre- and post-menopausal women. from the multi-ethnic study of atherosclerosis (MESA)

Abstract Background Endogenous sex hormones associated with both the left atrial (LA) and left ventricular (LV) structures in peri-menopausal women, but the association of menopause status with left atrioventricular coupling is not well established. Purpose To assess the prognostic value of a left atrioventricular coupling index (LACI) in pre- and post-menopausal women without a history of cardiovascular disease (CVD) at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods In women participating in the MESA study, the LACI was measured as the ratio of the left atrial (LA) end-diastolic volume to the left ventricular (LV) end-diastolic volume using cardiovascular magnetic resonance (CMR). Cox proportional hazard models were used to assess the association between the LACI and the outcomes of atrial fibrillation (AF), heart failure (HF), and hard CVD defined by myocardial infarction, resuscitated cardiac arrest, stroke, or coronary heart disease death. Results Among the 2,087 women participants (61±10 years), 485 cardiovascular events were observed during the mean follow-up period of 13.2±3.3 years. A higher LACI was independently associated with AF (HR 1.70; 95% CI [1.51–1.90]), HF (HR 1.62; [1.33–1.97]), and hard CVD (HR 1.30; [1.13–1.51], all p&amp;lt;0.001). Adjusted models with the LACI showed significant improvement in model discrimination and reclassification when compared to currently used standard models used to predict the incidence of AF (C-statistic=0.82 vs. 0.79; NRI=0.325; IDI=0.036), HF (C-statistic=0.84 vs. 0.81; NRI=0.571; IDI=0.023), hard CVD (C-statistic=0.78 vs. 0.76; NRI=0.229; IDI=0.012). Conclusion In a multi-ethnic population of pre- and post-menopausal women, the LACI is an independent predictor of HF, AF, and hard CVD. In both pre- and post-menopausal women, the LACI has an incremental prognostic value for predicting cardiovascular events over traditional risk factors and sex hormone levels. ClinicalTrials: gov Identifier: NCT00005487 Funding Acknowledgement Type of funding sources: None.