Progression Of Heart Failure In Patients Research Articles

Analysis and Prediction of Risk Factors for Heart Failure

Abstract. Heart failure is a grave and progressive illness. It is associated with multiple risk factors such as age and other possible factors. Accurately identifying and quantifying these risk factors is critical to developing personalized prevention and treatment strategies. However, it is difficult for common patients to predict heart failure without the professional diagnosis of doctors, and relying on human resources to predict heart failure is more subjective. This study proposes a method to evaluate and predict the factors related to heart failure based on multiple body indicators by using random forest algorithm. The random forest prediction model was applied to assess the correlation between multiple medical indicators such as creatinine phosphokinase (CPK), serum creatinine (SCR), ejection fraction (EF), age and heart failure. CPK was found to be the most associated with heart failure. In addition, increasing follow-up period can also effectively monitor heart failure progression in patients. In this high dimension prediction problem, the prediction effect of random forest is better, and the overall accuracy is higher. The approach used in this research is important for forecasting the risk of heart failure, enhancing the survival rates of patients, and alleviating the burden on healthcare systems.

Catheter ablation of atrial arrhythmias in cardiac amyloidosis: Impact on heart failure and mortality.

Atrial arrhythmias (AA) commonly affect patients with cardiac amyloidosis (CA) and are a contributing risk factor for the development of heart failure (HF). This study sought to investigate the long-term efficacy and impact of catheter ablation on HF progression in patients with CA and AA. Thirty-one patients with CA and AA undergoing catheter ablation were retrospectively included (transthyretin-ATTR CA 61% and light chain-AL CA 39%). AA subtypes included atrial fibrillation (AFib) in 22 (paroxysmal in 10 and persistent in 12), atrial flutter (AFl) in 17 and atrial tachycardia (AT) in 11 patients. Long-term AA recurrence rates were evaluated along with the impact of sinus rhythm (SR) maintenance on HF and mortality. AA recurrence was observed in 14 patients (45%) at a median of 3.5 months (AFib n = 8, AT n = 6, AFl = 0). Post-cardioversion, medical therapy or catheter ablation, 10 patients (32%) remained in permanent AA. Over a median follow-up of 19 months, all-cause mortality was 39% (n = 12): 3 with end-stage HF, 5 due to late complications of CA, 1 sudden cardiac death, 1 stroke, 1 COVID 19 (and one unknown). With maintenance of SR following catheter ablation, significant reductions in serum creatinine and natriuretic peptide levels were observed with improvements in NYHA class. Two patients required hospitalization for HF in the SR maintenance cohort compared to 5 patients in the AA recurrence cohort (p = 0.1). All 3 patients with deaths secondary to HF had AA recurrence compared to 11 out of the 28 patients whom were long-term survivors or deaths not related to HF (p = 0.04). All-cause mortality was not associated with AA recurrence. This study demonstrates moderate long-term efficacy of SR maintenance with catheter ablation for AA in patients with CA. Improvements in clinical and biological status with positive trends in HF mortality are observed if SR can be maintained.

Wireless Pulmonary Artery Pressure Monitor Implantation in a Patient with Duchenne Muscular Dystrophy.

Assessing heart failure progression in patients with Duchenne Muscular Dystrophy (DMD) is challenging given the multi-system nature of disease. Herein we describe the first case use of an implantable pulmonary artery pressure monitor and describe the potential clinical utility of this approach in patients with DMD.

The associations of cytokines and gens polymorphisms of β-adrenoceptors in patients with heart failure and some thyroid pathology (literature review and own observations).

Aim: To analyze the role of cytokines in the progression of heart failure (HF) in patients with concomitant pathology of the thyroid gland. Materials and Methods: The systematization of literature data on the role of cytokines in the progression of HF in patients with concomitant thyroid pathology (TP) was carried out. The results of our own research were presented. Conclusions: The final chapter in the history of the role of cytokines in the progression of HF has not yet been written. Further studies, including genetic ones, are necessary. The patients with HF have higher levels of TNFβ and IL-6, and a lower concentration of IL-4, compared to the control group. Patients with a fatal outcome of the disease, in contrast to those who survived for two years, have an increased level of TNFβ. In patients with concomitant TP, who had repeated hospitalization, a lower level was registered, compared to that under conditions of a more favorable course of heart failure. Concentrations of cytokines in the blood of patients with HF are associated with gene polymorphisms of the β-adrenoreceptor system: the C-allele of the Gly389A polymorphism of the β1-adrenoceptor gene leads to a decrease in the risk of increasing TNFα; IL-1α increases in the presence of the A-allele of the Ser49Gly polymorphism of this gene. In patients with HF and concomitant thyroid pathology, the risk of IL-6 growth increases in homozygous (C) patients for the Ser275 polymorphism of the β3 subunit of the G-protein.

Association of NPPB rs198389 and NPPA rs5068 single-nucleotide polymorphisms with natriuretic peptide levels and heart failure progression risks in patients with atrial fibrillation

Natriuretic peptides (NUPs) are the strongest predictors of poor prognosis in patients with heart failure (HF). Single-nucleotide polymorphisms (SNPs) rs198389 of the NPPB gene and rs5068 of the NPPA gene are associated with altered levels of NUP. The role of candidate gene polymorphisms in the activity of the NUP system and the association of NPPA/ NPPB SNPs with the risk of cardiovascular disease (CVD) in individuals with HF and atrial fibrillation (AF) is not well understood.The study aims to evaluate the allele and genotype frequencies of NPPA rs5068 and NPPB rs198389 SNPs in a selective sample of the Belarusian population, to determine the relationship of these SNPs with NUP concentrations, and to assess the prognostic significance of these SNPs on the risk of HF hospitalization in patients with HF and permanent AF.The study involved 187 patients. The main group included 152 patients with HF with left ventricular ejection fraction (LVEF) < 50 %. Group 1 included 48 patients with HF and AF; group 2 – 51 patients with HF and sinus rhythm (SR) and 35 patients in the control group. The levels of atrial and brain natriuretic peptides (ANP and BNP) and the N-terminal fragment of the brain natriuretic peptide (NT-proBNP) were determined. A genetic testing of polymorphic loci of the rs5068 NPPA gene and the rs198389 NPPB gene was performed. The primary endpoint of the study was hospitalization due to HF progression.The average observation period was 12.1 [from 9 to 14] months. The distribution of the genotype and allele frequencies of rs198389 NPPB and rs5068 NPPA in HF patients with LVEF < 50 % is comparable to that in individuals without CVD. In patients with HF and persistent AF, the minor allele C rs198389 NPPB is associated with higher BNP levels compared to patients with HF and SR (542 [333.7; 909.4] pg/ml versus 247.3 [244; 365.2] pg/ml; p < 0.05), but it has no relationship with the NT-proBNP level. In patients with HF and permanent AF, the ANP levels are not associated with rs5068 NPPA.The frequency of the T allele rs198389 NPPB in hospitalized patients was significantly lower compared to patients who were not hospitalized (22 patients (44 %) versus 83 patients (62 %); p = 0.04). The presence of the C allele rs198389 NPPB was associated with a higher risk of HF progression in patients with HF and AF, the odds ratio (OR) = 2.071 [95 % CI from 1.072 to 4.001], p < 0.05.

Renal tubular damage and clinical outcome in heart failure with preserved ejection fraction and chronic kidney disease.

Despite advances in heart failure (HF) treatment, HF with preserved ejection fraction (HFpEF) remains a health problem with a high mortality rate. HFpEF is composed of diverse phenogroups, of which patients with concomitant renal impairment have worse outcomes. Renal tubular damage (RTD) is associated with the development of HF and chronic kidney disease (CKD). However, the impact of RTD on HF progression in patients with HFpEF and CKD remains unclear. The aim of the present study was to examine whether RTD could predict HF-related events in patients with HFpEF and CKD. We measured RTD markers, such as urinary β2 -microglobulin to creatinine ratio (UBCR) and N-acetyl-β-d-glucosamidase (NAG) level, in 319 consecutive patients with HFpEF and CKD who were hospitalized for acute HF (49% females, mean age 76±12). Based on previous reports, high UBCR and high NAG levels were defined as UBCR ≥300μg/gCr and NAG >14.2U/gCr, respectively. There were 91 HF-related events, defined as HF hospitalizations or HF deaths, during the median follow-up period of 5.2years. The prevalence of high UBCR increased with advancing New York Heart Association functional class and albuminuria. Kaplan-Meier analysis demonstrated that patients with high UBCR had more HF-related events than those with normal or low UBCR. Multivariate Cox proportional hazards regression analyses demonstrated that high UBCR, but not high NAG level, was an independent predictor of HF-related events after adjusting for confounding risk factors in patients with HFpEF and CKD (hazard ratio, 2.60; 95% confidence interval, 1.52-4.72; P=0.0009). UBCR significantly improved the C-statistic, with a significant net reclassification index and integrated discrimination improvement (0.738 vs. 0.684; P=0.0244). RTD, as assessed by a high UBCR, was associated with the severity and clinical outcomes of HFpEF and CKD, indicating that it could be a feasible marker for HF progression.

New insights into the correlation between genotype and cardiac phenotype in laminopathies

Abstract Funding Acknowledgements Type of funding sources: None. Background Genotype-phenotype correlation and risk stratification for heart failure progression in patients with cardiolaminopathies are poorly defined. Purpose The primary aim of the present study is to characterize and correlate phenotype with genotype and sex. The secondary aim is to test the two main existing prognostic scores (the Arbustini and the Whabi score), both developed to predict ventricular arrhythmic events in cardiolaminopathies, for both major ventricular arrhythmias (MVA) and end-stage heart failure (ESHF). Methods This is a retrospective, single-center study, including patients with lamin (LMNA) and/or emerin (EMD) genetic variants. Data were collected from the first medical contact (FMC) to the last follow-up (FU). Results 28 patients (57% male, 82% probands, 68% with a family history of sudden death) were included: 96% harbored LMNA heterozygous variants, 15% had non-missense variants, 11% had variant previously never described. Functionally, 50% were variant of undetermined significance (VUS, C3), the rest were either pathogenetic or likely pathogenic (C4/C5) variants. Median age at FMC was 41 years (IQR 30-55 years), median FU was 11 years (IQR 8-18 years). At FMC, all patients had cardiac involvement, 54% had muscle involvement. By the last FU, 54% developed atrial fibrillation, 43% atrioventricular block (AVB) > I degree, 50% carried an implantable cardioverter defibrillator (21% with resynchronization), 50% had suffered at least one episode of MVA, 25% developed ESHF: 11% died due to refractory HF, 14% underwent heart transplantation (mean age 43.5 ± 9 years). The age of onset of the different types of cardiac phenotype was not influenced by sex. The penetrance of atrioventricular (AV) conduction defects (Figure 1 Panel A) and of atrial tachyarrhythmias (Figure 1 Panel B) was higher and earlier in subjects with non-missense variants. Subjects with VUS, compared to those with pathogenetic/likely pathogenetic variants, showed a significantly lower and later penetrance of MVA (Figure 2 Panel A) and a later penetrance of non- sustained ventricular tachycardia (NSVT, Figure 2, Panel B), but not of AV conduction disturbances, atrial arrhythmias, or contractile dysfunction. Arbustini score at FMC proved to be a predictor of both MVA and ESHF, while Whabi score only predicted MVA. Conclusions In our series, the prevalence and the age of appearance of the different cardiac phenotypes of cardiolaminopathies were not influenced by sex, while the presence of VUS correlated with a lower risk of ventricular arrhythmias, but not of the other cardiac manifestations including contractile disfunction and heart failure. Our data suggest the importance of a close cardiac monitoring and of larger prospective studies even in patients with VUS. All patients developed a sever cardiac phenotype by the age of 60.

The Risk of Heart Failure Progression in Patients With Patent Foramen Ovale: Differential Risk Associated With Device Closure

A patent foramen ovale (PFO) can unload left atrial pressure via an interatrial shunt. We investigated whether device closure of PFO is associated with a subsequent risk of heart failure (HF), particularly in patients with structural heart disease or atrial fibrillation (AF). We enrolled 4,804 consecutive patients who underwent transesophageal echocardiography at tertiary medical centers in Korea between 2007 and 2019. The primary outcome was the 4-year risk of HF hospitalization. Underlying structural heart disease was determined by echocardiography. A PFO was observed in 981 (20.4%) patients, where 161 underwent device closure. During follow-up (median, 3.5 [1.4-6.4] years), the primary outcome was lower in patients with PFO than in those without (2.6% vs 4.0%; adjusted hazard ratio [aHR], 0.65; 95% CI, 0.45-0.94; P=.021). Among the patients with PFO, the primary outcome was higher in the device closure group than in the no-closure group (5.5% vs 1.2%; aHR, 5.59; 95% CI, 4.26-7.34; P<.001). A consistent result was found in patients with structural heart disease or AF (9.6% vs 3.9%; aHR, 2.55; 95% CI, 1.95-3.33; P<.001), demonstrating an increased risk of the primary outcome proportionate to the number of combined structural abnormalities. However, no significant association was observed between the primary outcome and PFO closure in those without structural heart disease or AF (1.7% vs 1.5%; aHR, 1.22; 95% CI, 0.99-1.50; P=.054). Patients with underlying structural heart disease or AF may be predisposed to symptomatic HF progression after PFO closure. Therefore, careful medical surveillance with optimal risk management is needed in these patients.

Abstract 9538: Impact of Device Closure on Heart Failure Progression in Patients With Patent Foramen Ovale

Background: Patent foramen ovale (PFO) can unload left atrial pressure via interatrial shunt. We evaluated whether device occlusion of PFO is associated with subsequent risk of heart failure (HF). Methods: We enrolled 4,804 consecutive patients (median age: 68 years, 62.4% male) who underwent transesophageal echocardiography at tertiary medical centers in Korea between 2007 and 2019. The primary outcome was the 4-year risk of HF. The independent association of PFO closure with HF was evaluated using the Cox regression hazard model after multivariate adjustment for demographics, clinical risk factors, and echocardiographic parameters. Additional subgroup analysis was performed according to the presence structural heart disease defined as left ventricular (LV) ejection fraction &lt; 55%, left atrial (LA) size &gt; 35ml or LA volume ≥ 40ml/m 2 , LV mass index ≥ 115g/m 2 , E/e' ≥ 15, or presence of atrial fibrillation. Results: In total, PFO was observed in 981 (20.4%) patients, where 161 (16.4%) of them underwent device closure. Patients with PFO showed a lower risk of HF than those without (2.6 vs. 4.0%, adjusted hazard ratio [HR]: 0.65, 95% confidence interval [CI] 0.45-0.94, p=0.021). PFO closure group showed a significantly higher risk of HF than no closure group (5.5 vs. 1.2%, adjusted HR: 5.59, 95% CI 4.26-7.34, p&lt;0.001) (Figure). In subgroup analysis, PFO closure was significantly associated with HF risk in patients with underlying structural heart disease (9.6 vs. 3.9%, adjusted HR: 2.55, 95% CI 1.95-3.33, p&lt;0.001), demonstrating an increasing trend in proportion to the number of structural abnormalities. However, PFO closure showed no significant association with HF risk in patients without structural heart disease (1.7 vs. 1.5%, adjusted HR: 1.22, 95% CI 0.99-1.50, p=0.054). Conclusion: PFO closure may increase the risk of HF. Therefore, careful patient selection is needed, especially among those with underlying structural heart disease.

Atrial fibrillation and risk of progressive heart failure in patients with preserved ejection fraction heart failure.

Understanding of the pathophysiology of progressive heart failure (HF) in patients with heart failure with preserved ejection fraction (HFpEF) is incomplete. We sought to identify factors differentially associated with risk of progressive HF death and hospitalization in patients with HFpEF compared with patients with HF and reduced ejection fraction (HFrEF). Prospective cohort study of patients newly referred to secondary care with suspicion of HF, based on symptoms and signs of HF and elevated natriuretic peptides (NP), followed up for a minimum of 6years. HFpEF and HFrEF were diagnosed according to the 2016 European Society of Cardiology guidelines. Of 960 patients referred, 467 had HFpEF (49%), 311 had HFrEF (32%), and 182 (19%) had neither. Atrial fibrillation (AF) was found in 37% of patients with HFpEF and 34% with HFrEF. During 6years follow-up, 19% of HFrEF and 14% of HFpEF patients were hospitalized or died due to progressive HF, hazard ratio (HR) 0.67 (95% CI: 0.47-0.96; P=0.028). AF was the only marker that was differentially associated with progressive HF death or hospitalization in patients with HFpEF HR 2.58 (95% CI: 1.59-4.21; P<0.001) versus HFrEF HR 1.11 (95% CI: 0.65-1.89; P=0.7). De novo patients diagnosed with HFrEF have greater risk of death or hospitalization due to progressive HF than patients with HFpEF. AF is associated with increased risk of progressive HF death or hospitalization in HFpEF but not HFrEF, raising the intriguing possibility that this may be a novel therapeutic target in this growing population.

Factors associated with the risk of heart failure progression in patients with non-compaction cardiomyopathy

Abstract Purpose To identify factors associated with the progression of chronic heart failure (CHF) to NYHA FC III, requiring hospitalization and to reveal high-risk pts. Methods The study included 156 pts with non-compaction cardiomyopathy (NCCM), who were prospectively observed in the RSPC “Cardiology”. The median follow-up was 36 months (6; 152). All pts underwent echocardiography (Echo), cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) and 24-hour Holter monitoring. The median age of the pts was 36 (26; 49) years, men predominated (57.4%). The diagnosis of NCCM was established on the basis of the following criteria: Echo – Jenni criteria, CMR – Petersen/Jaquier criteria. The end point of the study included progression of CHF from NYHA FC II to FC III, requiring hospitalization. Results At the initial examination, symptoms of CHF NYHA FC I were found in 56 (55.4%) pts, symptoms of CHF NYHA FC II – in 45 (44.6%) pts, systolic dysfunction was detected in 43% of pts. During the follow-up period, out of 156 pts, 55 (35.3%) had CHF symptoms that progressed to NYHA FC III and required hospitalization. As a result of the bivariate analysis, the following Echo characteristics were independent factors associated with a high risk of progression of CHF to NYHA FC III: LV EF &amp;lt;40% (HR 6.2; 95% CI 3.4–11.2); end-diastolic LV diameter &amp;gt;62 mm (HR 5.3; 95% CI 2.9–9.7); end-systolic LV diameter &amp;gt;56 mm (HR 6.6; 95% CI 3.8–11.7); end-diastolic LV volume &amp;gt;187 ml (HR 4.4; 95% CI 2.5–8); end-systolic LV volume &amp;gt;93 ml (HR 6.5; 95% CI 3.2–13). The risk of progression of CHF to NYHA FC III was 3.4 times higher in pts with right ventricular (RV) systolic dysfunction: with a decrease of RV fractional area change (FAC) &amp;lt;31% (HR 3.4; 95% CI 1.8–6.3) and 2.5 times higher with a decrease of tricuspid annular plane systolic excursion (TAPSE) (HR 2.5; 95% CI 1.3–4.5); 2.5 times higher in pts with initially increased anteroposterior RV diameter &amp;gt;28 (HR 2.5; 95% CI 1,4–4.5). According to the LGE-CMR data, the factors associated with the risk of progression of CHF to NYHA FC III were the following characteristics: an increase of BSA-indexed end-diastolic LV volume &amp;gt;145 ml/m2 (HR 6.7; 95% CI 3.4–13.3); BSA-indexed end-systolic LV volume &amp;gt;96 ml/m2 (HR 6.8; 95% CI 3.4–13.6); and an increase of RV end-systolic volume &amp;gt;145 ml (HR 5.0; 95% CI 2.3–11). The risk of CHF progression was 4.8 times higher in pts with baseline LV systolic dysfunction (LV EF &amp;lt;34%, HR 4.8; 95% CI 2.8–8.2); 2.7 times higher in pts with RV systolic dysfunction (LVEF &amp;lt;42%, HR 2.7; 95% CI 1.6–4.8). The NC/C ratio and the presence of myocardial replacement fibrosis according to LGE-CMR did not significantly affect the risk of progression of CHF. Conclusion The factors identified as a result of the study associated with the risk of progression of CHF based on biventricular assessment by cardiac imaging methods (Echo and LGE-CMR) can be used to reveal high-risk pts. Funding Acknowledgement Type of funding sources: None.

Prognostic roles of obstructive sleep apnea syndrome and right ventricular dysfunction in heart failure patients with preserved ejection

Abstract Funding Acknowledgements Type of funding sources: None. Objective. To study the prognostic roles of obstructive sleep apnea syndrome (OSAS) and right ventricular dysfunction in the development of heart failure (HF) progression in patients with preserved ejection fraction (HFpEF) during the 12-month follow-up period. Methods. The severity of obstructive breathing disorders during sleep was assessed by the apnea/hypopnea index (AHI). A total of 86 men, median age of 62.0 (41.0; 78.0) years with moderate and severe OSAS (with AHI &amp;gt; 15 per hour) and HF of NYHA class I-III with baseline LVEF of 60% [52; 65]% were enrolled in the study. All patients had the abdominal obesity (WC &amp;gt; 92 cm), body mass index exceeded 30 kg/m2. Serum levels of NT-proBNP were measured using ELISA at baseline. Two-dimensional transthoracic echocardiography with assessment of right ventricular function and 6-minute walk test were performed at baseline and at 12 months. Results. At 12 months of follow-up period all patients were divided into 2 groups: group 1 (n = 33) comprised patients with HF progression, group 2 (n = 53) without it. The concentration of NT-proBNP at baseline was higher by 18% in group 1 than in group 2 (p = 0.024; 338 [168; 678] vs. 278 [177; 815] pg/mL, respectively). The median values of AHI (p &amp;lt; 0.0001) were 46.0 [20.6; 85] per hour in group 1 and 24.0 [21.0; 28.0] per hour in group 2. In group 1 than in group 2 fractional change in the area of the right ventricle (ΔSRV) was less by 9.1% (p = 0.031; 40 [35; 47] vs. 44 [40; 47]%, respectively) and right ventricular myocardial function index (RVSWI, Tey index) was less by 8% (p = 0.022; 0.23 [0.22; 0.25] vs. 0.25 [0.24; 0.26], respectively). Based on ROC-analysis, AHI ≥33.5 episodes per hour (sensitivity 75.8%, specificity 67.9%, AUC = 0.732; p &amp;lt; 0.0001), ΔSRV ≤18.6% (sensitivity 75.8%, specificity 54.7%, AUC = 0.62; p = 0.047) and NT-proBNP ≥311 pg/mL (sensitivity 63.6%, specificity 73.6%, AUC = 0.645; p &amp;lt; 0.0001) were identified as a cut-off values predicting the development of HF progression. The combined evaluation of NT-proBNP and AHI increased the predictive value of the analysis (sensitivity of 82.6%, specificity of 77.1%, and AUС of 0.821; p &amp;lt; 0.0001). Conclusion. Our data suggest that NT-proBNP, AHI and ΔSRV may be used as a diagnostic biomarker for HF progression in patients with preserved ejection fraction (HFpEF) during the 12-month follow-up period. The combined use of NT-proBNP and AHI demonstrated higher diagnostic sensitivity and specificity for prediction of unfavorable course of HF.

Usefulness of Global Longitudinal Strain to Predict Heart Failure Progression in Patients With Nonobstructive Hypertrophic Cardiomyopathy

While predicting prognosis to anticipate adverse disease course has long been an aspiration in hypertrophic cardiomyopathy (HC), reliable markers of progressive and unrelenting heart failure symptoms in the absence of obstruction are not well characterized. We sought to evaluate markers of systolic function, including the role of global longitudinal strain (GLS), to identify nonobstructive HC patients at risk for future heart failure. A cohort of 296 consecutive nonobstructive HC patients (42 ± 18years; 75% male) with NYHA class I/II symptoms and preserved systolic function at study entry (EF: 65 ± 6%), were followed for progressive heart failure symptoms (increase in ≥ 1 NYHA functional class) and/or development of systolic dysfunction (EF < 50%). Over median follow-up of 4 ± 3 years, 35 study patients (10%) experienced new heart failure events, including 31 with progressive symptoms and 4 who developed systolic dysfunction. Abnormal GLS < 16% was associated with a 5-fold increase in risk for heart failure compared to GLS > 18% (p < 0.001). GLS remained an independent predictor of heart failure even after adjustment for other relevant disease variables including EF (OR 1.23, p = 0.005). However, notably, when GLS and EF were combined, the prediction of heart failure for individual patients was enhanced (net reclassification improvement 0.55; p = 0.002). Together, GLS < 16% and EF 50% to 59% were associated with a 12.5-fold greater risk for heart failure versus patients with GLS > 18% and EF ≥ 60%, who were at the lowest risk. In conclusion, in nonobstructive HC with no or mild symptoms and preserved EF, abnormal GLS is a strong independent predictor for subsequent development of progressive heart failure symptoms and/or systolic dysfunction. Furthermore, the greatest power in predicting outcome in nonobstructive HC is achieved by combining GLS with EF to identify HC patients at the highest risk for heart failure progression and systolic dysfunction.

The predictive value of epicardial adipose tissue volume assessed by cardiac magnetic resonance for atrial fibrillation in patients with hypertrophic obstructive cardiomyopathy.

Atrial fibrillation (AF) is the most common arrhythmia and potentially increase the risk of embolic stroke and aggravate progressive heart failure in patients with hypertrophic cardiomyopathy (HCM). Recent studies demonstrated that epicardial adipose tissue (EAT) was closely associated with AF in general population. However, the relationship between EAT and AF in HCM patients remains unclear. A total of 93 consecutive patients with hypertrophic obstructive cardiomyopathy (HOCM) at Fuwai Hospital were enrolled in our study. There were 18 patients with AF and 75 patients without it. Cardiac magnetic resonance (CMR) imaging was performed in all participants. EAT volume (EATV) and left atrial volume (LAV) were determined by E-3D medical model software. HOCM patients with AF had significantly greater EATV index (EATVI, P < 0.001), LAV index (LAVI, P < 0.001) and left ventricular end-systole volume index (LVESVI, P = 0.039), and lower left ventricular ejection fraction (LVEF, P = 0.002). In multivariable logistic regression analysis, EATVI, LAVI, and LVEF remained independent determinants of AF occurrence (OR = 1.023, 95% CI, 1.003-1.043, P = 0.023, OR = 1.043, 95% CI, 1.012-1.075, P = 0.006, and OR = 0.887, 95% CI, 0.818-0.962, P = 0.004, respectively). Furthermore, receiver operating characteristic (ROC) curve analysis demonstrated that integration of EATVI, LAVI and LVEF provided better discriminatory performance for incident AF in HOCM patients with a high sensitivity of 94.4% and a specificity of 69.3% (AUC = 0.864, 95% CI, 0.771-0.958, P < 0.001). EATVI is an independent predictor of the presence of AF, and integration of EATVI, LVEF and LAVI determined by CMR provide greater discriminatory performance for identifying AF in HOCM patients.

Psychosocial Stress Hastens Disease Progression and Sudden Death in Mice with Arrhythmogenic Cardiomyopathy.

Physiological stressors, such as exercise, can precipitate sudden cardiac death or heart failure progression in patients with arrhythmogenic cardiomyopathy (ACM). Yet, whether and to what extent a highly prevalent and more elusive environmental factor, such as psychosocial stress (PSS), can also increase ACM disease progression is unexplored. Here, we first quantified perceived stress levels in patients with ACM and found these levels correlated with the extent of arrhythmias and cardiac dysfunction. To determine whether the observed correlation is due to causation, we inflicted PSS-via the resident-intruder (RI) paradigm—upon Desmoglein-2 mutant mice, a vigorously used mammalian model of ACM. We found that ACM mice succumbed to abnormally high in-trial, PSS mortality. Conversely, no sudden deaths occurred in wildtype (WT) counterparts. Desmoglein-2 mice that survived RI challenge manifested markedly worse cardiac dysfunction and remodeling, namely apoptosis and fibrosis. Furthermore, WT and ACM mice displayed similar behavior at baseline, but Desmoglein-2 mice exhibited heightened anxiety following RI-induced PSS. This outcome correlated with the worsening of cardiac phenotypes. Our mouse model demonstrates that in ACM-like subjects, PSS is incisive enough to deteriorate cardiac structure and function per se, i.e., in the absence of any pre-existing anxious behavior. Hence, PSS may represent a previously underappreciated risk factor in ACM disease penetrance.

Age-Dependent Echocardiographic and Pathologic Findings in a Rat Model with Duchenne Muscular Dystrophy Generated by CRISPR/Cas9 Genome Editing.

Duchenne muscular dystrophy (DMD) is X-linked recessive myopathy caused by mutations in the dystrophin gene. Although conventional treatments have improved their prognosis, inevitable progressive cardiomyopathy is still the leading cause of death in patients with DMD. To explore novel therapeutic options, a suitable animal model with heart involvement has been warranted.We have generated a rat model with an out-of-frame mutation in the dystrophin gene using CRISPR/Cas9 genome editing (DMD rats). The aim of this study was to evaluate their cardiac functions and pathologies to provide baseline data for future experiments developing treatment options for DMD.In comparison with age-matched wild rats, 6-month-old DMD rats showed no significant differences by echocardiographic evaluations. However, 10-month-old DMD rats showed significant deterioration in left ventricular (LV) fractional shortening (P = 0.024), and in tissue Doppler peak systolic velocity (Sa) at the LV lateral wall (P = 0.041) as well as at the right ventricular (RV) free-wall (P = 0.004). These functional findings were consistent with the fibrotic distributions by histological analysis.Although the cardiac phenotype was milder than anticipated, DMD rats showed similar distributions and progression of heart involvement to those of patients with DMD. This animal may be a useful model with which to develop effective drugs and to understand the underlying mechanisms of progressive heart failure in patients with DMD.

Beta-adrenergic reactivity of erythrocytes and the progression of heart failure in patients after myocardial infarction

Aim. To identify the associations between beta-adrenergic reactivity of erythrocytes and the progression of heart failure (HF) in patients after myocardial infarction (MI).Material and methods. The study included 50 patients with HF and history of MI 6 months ago. To determine the level of sympathoadrenal system activity, we analyzed beta-adrenergic reactivity by changing the osmotic resistance of erythrocytes by use of adrenoceptor blocking agent.Results. The frequency of HF progression after index MI was 26% (n=13). All patients were divided into 2 groups depending on the presence/absence of HF progression in the postinfarction period. When determining beta-adrenergic reactivity, it was found that patients with HF progression compared with patients without it had the higher level of beta-adrenergic reactivity of membrane (β-ARM) of erythrocytes: 58,8 (50,9; 78,0) CU and 46,8 (38,0; 66,3) CU, p=0,025). A ROC analysis made it possible to establish the β-ARM level ≥49,53 CU a cut-off point, which can be considered as a marker of HF progression in patients after MI (sensitivity 92,3%, specificity 62,2%). This level of β-ARM is associated with a more than five-fold increase of HF progression risk in patients after MI (OR 5,48; 95% CI 1,28-23,37; p=0,024).Conclusion. In patients with HF and MI history, there is a decrease in the adrenergic reactivity of erythrocyte cell membrane, which is reflected by an increase of β-ARM above normal range of 20 CU. At the same time, β-ARM in patients with HF progression compared with patients without it is significantly increased. Established cut-off point of β-ARM (≥49,53 CU) allows predicting the HF progression with high sensitivity and specificity.

Risk of heart failure progression in patients with reduced ejection fraction: mechanisms and therapeutic options.

Transition from stage C to stage D of heart failure (HF) represents an irreversible process toward end-stage disease. Crucial interventions to be adopted in the attempt to interfere with this process are represented by the identification of patients at high risk to develop HF progression and by an effective and prompt management. Markers of worse prognosis and disease progression are well established and include recurrence of HF decompensation, intolerance to the neurohormonal standard pharmacological treatment, and resistance to loop diuretics. In addition, both NT-proBNP and sympathetic nervous system (SNS) overdrive are strong predictors of adverse clinical outcome and allow to identify high-risk HF patients even in the presence of mild symptoms. To counteract the deleterious effects of the SNS activation, new strategies such as a new drug combining angiotensin receptor and neprilysin inhibition and baroreceptor stimulation therapy (BAT) have been investigated. Inability to properly counteract the SNS overdrive leads to acute HF decompensation by different mechanisms. The leading ones are represented by the progressive sodium and water retention with fluid overload and by the blood volume redistribution between splanchnic and non-splanchnic regions. The correct understanding of these mechanisms, together with the availability of new therapeutic options such as peritoneal ultrafiltration, represent the rationale but not infrequently overlooked therapeutic options to improve congestion management in HF patients.

Myocardial Ischemia Correlates with Left Ventricular Systolic Dysfunction in Patients with Noncompaction Cardiomyopathy

Purpose Noncompaction cardiomyopathy (NCC) results as an arrest of the myocardial compaction process in the embryonic period, leading to the impaired formation of the microvasculature. Myocardial perfusion abnormalities have already been described, however, the functional impact in NCC patients remains undefined. We sought to analyze a potential correlation between myocardial ischemia and heart failure progression in patients with NCC. Methods We enrolled 37 (24 male, 13 female) patients with NCC, average age 47±15 years. Echocardiography determined left ventricular end diastolic diameter and volume (EDD and EDV) and ejection fraction (LVEF). Global longitudinal strain (GLS) postprocessing has been performed. Serum levels of NT-proBNP have been measured. Cardiac MRI has been performed to confirm the diagnosis. Myocardial SPECT was performed at rest and on stress, determining summed difference score (SDS). Significant myocardial ischemia was defined as SDS≥2. Results Myocardial ischemia has been shown in 15 patients (41%, Group A), 22 patients (59%) showed no significant ischemic changes (Group B). The two groups did not differ in sex (male 73% vs. 59% in Group B), age (48±15 years vs. 46±14 years, P=0.65), creatinine (76±14 μmol/L vs. 76±16 μmol/L, P=0.98) or bilirubin (11±6 μmol/L vs. 12±5 μmol/L, P=0.46). When compared to Group B, Group A had significantly lower LVEF (38±15% vs. 55±13% in Group B, P=0.001), higher EDD (6.3±0.9 cm vs. 5.2±0.7 cm, P Conclusion In patients with NCC myocardial ischemia correlates with lower ejection fraction and dilation of the left ventricle, leading to greater neurohumoral activation. As medical heart failure therapy has not been shown to be successful in NCC patients, progressive LV systolic dysfunction due to myocardial ischemia often warrants heart transplantation or left ventricular assist device implantation. Treatment approaches targeting myocardial ischemia, such as CD34+ cell therapy, could slow the progression of disease in NCC patients.

Differential Gene Expression Profile of Renin-Angiotensin System in the Left Atrium in Mitral Regurgitation Patients.

Background Left atrial enlargement is a mortality and heart failure risk factor in primary mitral regurgitation (MR) patients. Pig models of MR have shown differential expression of genes linked to the renin-angiotensin system. Therefore, the aim of this study was to investigate the key genes of the renin-angiotensin that are expressed differentially in the left atrial myocardium in MR patients. Methods Quantitative RT-PCR was used to compare gene expression in the renin-angiotensin system in the left atrium in MR patients, aortic valve disease patients, and normal subjects. Results Plasma angiotensin II concentrations did not significantly differ between MR patients and aortic valve disease patients (P = 0.582). Compared to normal controls, however, MR patients had significantly downregulated expressions of angiotensin-converting enzyme, angiotensin I converting enzyme 2, type 1 angiotensin II receptor, glutamyl aminopeptidase, angiotensinogen, cathepsin A (CTSA), thimet oligopeptidase 1, neurolysin, alanyl aminopeptidase, cathepsin G, leucyl/cystinyl aminopeptidase (LNPEP), neprilysin, and carboxypeptidase A3 in the left atrium. The MR patients also had significantly upregulated expressions of MAS1 oncogene (MAS1) and mineralocorticoid receptor compared to normal controls. Additionally, in comparison with aortic valve disease patients, MR patients had significantly downregulated CTSA and LNPEP expression and significantly upregulated MAS1 expression in the left atrium. Conclusions Expressions of genes in the renin-angiotensin system, especially CTSA, LNPEP, and MAS1, in the left atrium in MR patients significantly differed from expressions of these genes in aortic valve disease patients and normal controls. Notably, differences in expression were independent of circulating angiotensin II levels. The results of this study provide a rationale for pharmacological therapies or posttranslational regulation therapies targeting genes expressed differentially in the renin-angiotensin system to remedy structural remodeling associated with atrial enlargement and heart failure progression in patients with MR.