Non-ischemic Heart Failure Patients Research Articles

Impact of left bundle branch block morphology in predicting response to left bundle branch area pacing for cardiac resynchronization therapy

Abstract Background Left bundle branch area pacing (LBBAP) is a novel pacing technique with an emerging role in resynchronization therapy [1-4]. QRS morphology has shown to significantly influence cardiac resynchronization therapy (CRT) response [5-6]. Purpose The aim of this study was to assess whether different left bundle branch block (LBBB) definitions are associated with response to LBBAP resynchronization therapy. Methods 40 consecutive CRT candidates with previously unsuccessful biventricular (BiV) pacing or in which effective CRT could not be achieved with BiV pacing based on anatomical or functional criteria were selected for this study. Both ischemic and non-ischemic heart failure (HF) patients were included. Patients were divided into two groups according to LBBB morphology. Group 1 included 20 patients (45% ischemic HF) with strict LBBB definition according to Strauss criteria [7], while 20 patients in Group 2 (55% ischemic HF) had conventional LBBB morphology. Response to CRT was defined for (1) reduction in QRS duration; (2) increase in left ventricular ejection fraction (LVEF) ≥ 5% and (3) decrease in left ventricular end systolic volume (LVESV) ≥ 15%. Results LBBAP was successfully achieved in all patients (mean age: 72.0 years; male: 29). The mean baseline QRS duration before implantation was 178.6±13.8 in the Group 1 and 170.8±29.4 in the Group 2, without a statistically significant difference. Over a mean follow-up of 5.6 months, LBBAP resulted in QRS narrowing in both groups, with a greater reduction in Group 1 (-40.6 ms) compared to Group 2 (-15.1 ms), (p 0.002). Pre-implantation ventricular systolic function did not show significant differences between the two groups, with a mean of 30.1±3.5% in the Strauss LBBB group and 31.0±6.0% in the conventional LBBB group. After implantation LVEF was 42.1±8.5 % in the true LBBB patients and 33.2±7.5 in the conventional LBBB group. Echocardiographic response was observed in 65% of patients with a statistically significant difference between Group 1 (90% of responders) and Group 2 (40% of responders), (p 0,001). HF etiology did not impact the response to LBBAP CRT. Conclusions Strict LBBB definition is associated to a greater electrocardiographic and echocardiographic response in patients receiving LBBAP CRT compared to conventional LBBB criteria.\

Efficacy of Native T1 Mapping for Patients With Non-Ischemic Cardiomyopathy and Ventricular Functional Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair.

We investigated the efficacy of left ventricular (LV) myocardial damage by native T1mapping obtained with cardiac magnetic resonance (CMR) for patients undergoing transcatheter edge-to-edge repair (TEER).Methods and Results: We studied 40 symptomatic non-ischemic heart failure (HF) patients and ventricular functional mitral regurgitation (VFMR) undergoing TEER. LV myocardial damage was defined as the native T1Z-score, which was converted from native T1values obtained with CMR. The primary endpoint was defined as HF rehospitalization or cardiovascular death over 12 months after TEER. Multivariable Cox proportional hazards analysis showed that the native T1Z-score was the only independent parameter associated with cardiovascular events (hazard ratio 3.40; 95% confidential interval 1.51-7.67), and that patients with native T1Z-scores <2.41 experienced significantly fewer cardiovascular events than those with native T1Z-scores ≥2.41 (P=0.001). Moreover, the combination of a native T1Z-score <2.41 and more severe VFMR (effective regurgitant orifice area [EROA] ≥0.30 cm2) was associated with fewer cardiovascular events than a native T1Z-score ≥2.41 and less severe VFMR (EROA <0.30 cm2; P=0.002). Assessment of baseline LV myocardial damage based on native T1Z-scores obtained with CMR without gadolinium-based contrast media is a valuable additional parameter for better management of HF patients and VFMR following TEER.

The Role of CCTA-derived Cardiac Structure and Function Analysis in the Prediction of Readmission in Nonischemic Heart Failure

Cardiac function and structure significantly impact nonischemic heart failure (HF) patient outcomes. This study investigated 236 patients (107 nonischemic heart failure, 129 healthy) to assess the relationship between coronary computed tomography angiography (CCTA)-derived parameters and clinical outcomes. Among the nonischemic heart failure patients, 37.3% experienced readmissions. In this group, specific CCTA measurements were identified as significant predictors of readmission: epicardial adipose tissue (CTEAT) at 54.49 cm3 (HR: 1.05; 95% CI: 1.03–1.07; P < 0.001), cardiac muscle mass to lumen volume (CTV/M) at 20% (HR: 0.59; 95% CI: 0.48–0.72; P < 0.001), peri-coronary adipose (CTPCAT) at -64.68 HU (HR: 1.1; 95% CI: 1.03–1.16; P = 0.002) for the right coronary artery, -81.07 HU (HR: 1.3; 95% CI: 1.1–1.53; P = 0.002) for the left anterior descending artery, and -73.42 HU (HR: 1.33; 95% CI: 1.18–1.51; P < 0.001) for the circumflex branch of the left coronary artery. In patients with nonischemic heart failure, increased CTEAT, CTPCAT, and CTV/M independently predicted rehospitalization.Graphical

Incorporating inflammatory biomarkers into a prognostic risk score in patients with non-ischemic heart failure: a machine learning approach.

Inflammation is involved in the mechanisms of non-ischemic heart failure (NIHF). We aimed to investigate the prognostic value of 21 inflammatory biomarkers and construct a biomarker risk score to improve risk prediction for patients with NIHF. Patients diagnosed with NIHF without infection during hospitalization were included. The primary outcome was defined as all-cause mortality and heart transplantations. We used elastic net Cox regression with cross-validation to select inflammatory biomarkers and construct the best biomarker risk score model. Discrimination, calibration, and reclassification were evaluated to assess the predictive value of the biomarker risk score. Of 1,250 patients included (median age, 53 years, 31.9% women), 436 patients (34.9%) experienced the primary outcome during a median of 2.8 years of follow-up. The final biomarker risk score included high-sensitivity C-reactive protein-to-albumin ratio (CAR) and red blood cell distribution width-standard deviation (RDW-SD), both of which were 100% selected in 1,000 times cross-validation folds. Incorporating the biomarker risk score into the best basic model improved the discrimination (ΔC-index = 0.012, 95% CI 0.003-0.018) and reclassification (IDI, 2.3%, 95% CI 0.7%-4.9%; NRI, 17.3% 95% CI 6.4%-32.3%) in risk identification. In the cross-validation sets, the mean time-dependent AUC ranged from 0.670 to 0.724 for the biomarker risk score and 0.705 to 0.804 for the basic model with a biomarker risk score, from 1 to 8 years. In multivariable Cox regression, the biomarker risk score was independently associated with the outcome in patients with NIHF (HR 1.76, 95% CI 1.49-2.08, p < 0.001, per 1 score increase). An inflammatory biomarker-derived risk score significantly improved prognosis prediction and risk stratification, providing potential individualized therapeutic targets for NIHF patients.

Prognostic value of mitral regurgitation in patients with heart failure undergoing cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac resynchronization therapy (CRT) is a well-established treatment for specific groups of heart failure (HF) patients. CRT improves outcomes in ischemic and non-ischemic HF patients, depending on different predictors. Mitral regurgitation (MR) is a common echocardiographic finding with uncertain reported impact on prognosis. Purpose We sought to investigate clinical outcomes in HF patient undergoing CRT according to MR severity, for both ischemic and non-ischemic HF etiology. A transthoracic echocardiogram was performed before and 1-year after device-based therapy to all patients (in doubtful cases, a cardiac magnetic resonance imaging was also performed to evaluate the mitral regurgitant volume). Methods Single-center retrospective study of consecutive patients submitted to CRT implantation. Patients were stratified attending to MR at baseline and after CRT, as having significant (moderate and severe MR) or non-significant MR. The primary endpoint was a composite of major adverse cardiac events (MACE), including HF hospitalization or all-cause mortality. Sustained ventricular arrhythmic events were the secondary endpoint. Results 117 HF patients (mean age 71.1 ± 10.6 years, males 67.5%) were enrolled, 31.6% had an ischemic HF etiology and 23.9% were included in the baseline significant MR (SMR) group. Regarding baseline characteristics, 40.2% had atrial fibrillation (AF), 23.9% obstructive pulmonary disease (COPD) and 9% peripheral artery disease (PAD). Patients in SMR group had more dyslipidemia (p = 0.026) and lower left ventricular ejection fraction (median 25% vs 32%, p = 0.001). At 1-year of follow-up, 11.1% had significant MR, most (61.5%) with the same MR baseline degree and presented with higher NYHA class (p = 0.032). During the follow-up, 15.4% reached the primary endpoint while 8.5% the secondary endpoint. Ischemic etiology (p = 0.204, p = 0.191) and the severity of baseline MR (p = 0.106, p = 0.213) did not predict any of the endpoints. On the contrary, male gender (p = 0.033), alcohol consumption (p = 0.003), PAD (p = 0.004) and COPD (p = 0.005) were independent predictors for MACE endpoint at a multivariable analysis. For the secondary endpoint, PAD (p = 0.020) and AF (p = 0.001) were both significant predictors. Significant MR after CRT implantation was an independent strong predictor only for MACE outcome (HR 4.37, p = 0.014). Conclusions Baseline significant MR was not associated with clinical outcomes after CRT implantation. However, MR at follow-up was a strong determinant of higher mortality and HF hospitalizations in more symptomatic patients, regardless of HF etiology.

Plasma Galectin-3 and H-FABP correlate with poor physical performance in patients with congestive heart failure.

Heart failure (HF) is often associated with compromised physical capacity in patients. However, it is unclear if established HF markers correlate with the physical performance of patients with congestive HF (CHF). We assessed the left ventricular end-systolic dimension (LVESD) and ejection fraction (LVEF) and, physical performance parameters, including short physical performance battery (SPPB), gait speed (GS), and handgrip strength (HGS) in 80 patients with CHF along with 59 healthy controls. Furthermore, levels of plasma HF markers galectin-3 and heart-specific fatty acid binding protein (H-FABP) were measured in relation to the severity of HF and physical performance. Irrespective of etiology, significantly greater LVESD and lower LVEF were observed in HF patients versus controls. As expected, the levels of HF markers galectin-3 and H-FABP were upregulated in the CHF patients which were accompanied by significantly elevated levels of plasma zonulin and inflammatory marker C-reactive protein (CRP). The SPPB scores, GS, and HGS were significantly lower in the ischemic and non-ischemic HF patients than controls. The level of galectin-3 was inversely correlated with SPPB scores (r2 = 0.089, P = 0.01) and HGS (r2 = 0.078, P = 0.01). Similarly, H-FABP levels were also inversely correlated with SPPB scores (r2 = 0.06, P = 0.03) and HGS (r2 = 0.109, P = 0.004) in the patients with CHF. Taken together, CHF adversely affects physical performance, and galectin-3 and H-FABP may serve as biomarkers of physical disability in patients with CHF. The robust correlations of galectin-3 and H-FABP with the physical performance parameters and CRP in CHF patients suggest that the poor physical performance may partly be caused due to systemic inflammation.

Update in LV Only Fusion CRT Pacing: Annals and Future Perspectives.

Triple-chamber cardiac devices are utilized for cardiac resynchronization therapy (CRT) and is the standard-of-care therapy for heart failure (HF) patients in the current guidelines. In the setting of biventricular (BIV) pacing it involves a mandatory implantation of right ventricular (RV) lead that allows simultaneous BIV pacing with 0 ms VV (ventricular to ventricular) interval. Nevertheless, it seems that response to CRT is not related to RV lead position. RV pacing is known for deleterious effects on RV/Left Ventricle (LV) function and should not be used in persons with normal atrioventricular conduction (AV) and sinus rhythm. As it compensates for the additional asynchrony induced by unnecessary stimulation of RV pacing, only pacing the left ventricle (LV) may result in improved cardiac resynchronization therapy (CRT) outcomes and a decrease in the number of individuals who do not respond to the procedure. Furthermore, leadless LV fusion CRT pacing without RV lead could be a potential CRT therapy alternative to BIV pacing in nonischemic heart failure patients with preserved AV conduction. The aim of our study is to made an update in cardiac resynchronization therapy with LV only fusion pacing.

Receptor autoantibodies: Associations with cardiac markers, histology, and function in human non-ischaemic heart failure.

A causal link between non-ischaemic heart failure (HF) and humoral autoimmunity against G-protein-coupled receptors (GPCR) remains unclear except for Chagas' cardiomyopathy. Uncertainty arises from ambiguous reports on incidences of GPCR autoantibodies, spurious correlations of autoantibody levels with disease activity, and lack of standardization and validation of measuring procedures for putatively cardio-pathogenic GPCR autoantibodies. Here, we use validated and certified immune assays presenting native receptors as binding targets. We compared candidate GPCR autoantibody species between HF patients and healthy controls and tested associations of serum autoantibody levels with serological, haemodynamic, metabolic, and functional parameters in HF. Ninety-five non-ischaemic HF patients undergoing transcatheter endomyocardial biopsy and 60 healthy controls were included. GPCR autoantibodies were determined in serum by IgG binding to native receptors or a cyclic peptide (for β1AR autoantibodies). In patients, cardiac function, volumes, and myocardial structural properties were assessed by cardiac magnetic resonance imaging; right heart catheterization served for determination of cardiac haemodynamics; endomyocardial biopsies were used for histological assessment of cardiomyopathy and determination of cardiac mitochondrial oxidative function by high-resolution respirometry. Autoantibodies against β1 adrenergic (β1 AR) , M5-muscarinic (M5AR), and angiotensin II type 2 receptors (AT2R) were increased in HF (all P<0.001). Autoantibodies against α1 -adrenergic (α1 AR) and angiotensin II type 1 receptors (AT1R) were decreased in HF (all P<0.001). Correlation of alterations of GPCR autoantibodies with markers of cardiac or systemic inflammation or cardiac damage, haemodynamics, myocardial histology, or left ventricular inflammation (judged by T2 mapping) were weak, even when corrected for total IgG. β1 AR autoantibodies were related inversely to markers of left ventricular fibrosis indicated by T1 mapping (r=-0.362, P<0.05) and global longitudinal strain (r=-0.323, P<0.05). AT2R autoantibodies were associated with improved myocardial mitochondrial coupling as measured by high-resolution respirometry in myocardial biopsies (r=-0.352, P<0.05). In insulin-resistant HF patients, AT2R autoantibodies were decreased (r=-.240, P<0.05), and AT1R autoantibodies were increased (r=0.212, P<0.05). GPCR autoantibodies are markedly altered in HF. However, they are correlated poorly or even inversely to haemodynamic, metabolic, and functional markers of disease severity, myocardial histology, and myocardial mitochondrial efficiency. These observations do not hint towards a specific cardio-pathogenic role of GPCR autoantibodies and suggest that further investigations are required before specific therapies directed at GPCR autoantibodies can be clinically tested in non-ischaemic HF.

Predicting the survival benefit of cardiac resynchronization therapy with defibrillator function for non-ischemic heart failure-Role of the Goldenberg risk score.

Primary prevention of sudden cardiac death (SCD) in non-ischemic heart failure (HF) patients remains a topic of debate at cardiac resynchronization therapy (CRT) implantation requiring individual risk assessment. Using the Goldenberg SCD risk score, we aimed to predict, which non-ischemic HF patients will benefit from the addition of an implantable cardioverter defibrillator (ICD) to CRT at long-term. Between 2000 and 2018 non-ischemic HF patients undergoing CRT implantation were collected into our retrospective registry. The Goldenberg risk score (GRS) was calculated by the presence of atrial fibrillation, New York Heat Association (NYHA) class > 2, age > 70 years, blood urea nitrogen > 26 mg/dl and QRS > 120 ms. The primary endpoint was all-cause mortality, heart transplantation or left ventricular assist device implantation. From 667 patients, 347 (52%) underwent cardiac resynchronization therapy-pacemaker (CRT-P), 320 (48%) cardiac resynchronization therapy-defibrillator (CRT-D) implantations. During the median follow up time of 4.3 years, 306 (46%) patients reached the primary endpoint (CRT-D 37% vs. CRT-P 63%; p < 0.001). CRT-D patients were younger (64 vs. 69 years; p < 0.001), infrequently females (26 vs. 39%; p < 0.001), and had a lower ejection fraction (27 vs. 29%; p < 0.01) compared to CRT-P patients. After GRS calculation, patients were dichotomized by low (< 3) and high (≥ 3) scores. CRT-D patients with low GRS showed a mortality benefit compared to CRT-P (HR 0.68; 95% CI 0.48-0.96; p = 0.03), high-risk patients did not (HR 0.84; 95% CI 0.62-1.13; p = 0.26). In our non-ischemic cohort, patients with low GRS showed a clear long-term mortality benefit by adding ICD to CRT, however, in high-risk patients no further benefit could be observed.

Prognostic Significance of High-Sensitivity Troponin T in Nonischemic Heart Failure with Reduced Ejection Fraction.

Cardiac biomarkers can help diagnose and predict heart failure prognosis. High-sensitivity troponin T has frequently been investigated in ischemic heart failure studies. However, the relation between high-sensitivity troponin T and mortality in nonischemic heart failure and its level indicating poor prognosis remain unclear. This study aimed to show whether high-sensitivity troponin T is a predictor of all-cause mortality and the cut-off value for high-sensitivity troponin T in patients with nonischemic heart failure with reduced ejection fraction. We included 249 nonischemic heart failure patients with left ventricular ejection fraction ≤ 40%, age ≥ 18 years, and high-sensitivity troponin T level known. Of the patients, 59.8% were male, 73.5% were New York Heart Association I or II, and the median age was 64. High-sensitivity troponin T value of the patients was 18 ng/L [inter-quartile range, 10-34]. The cut-off value of high-sensitivity troponin T for all-cause mortality was 21.5 ng/L, with 72.6% sensitivity and 69.9% specificity (area under the curve: 0.760, 95% CI: 0.692-0.828, P < 0.001). Patients were compared according to the 21.5 ng/L high-sensitivity troponin T cut-off value. At 30-month follow-up, all-cause mortality was 29.3%. According to the Kaplan-Meier analysis, the mortality rate was 14% in the high-sensitivity troponin T < 21.5 ng/L group, while the mortality rate was 50% in the high-sensitivity troponin T ≥ 21.5 ng/L group (P < 0.001, log-rank test). Baseline high-sensitivity troponin T was inde-pendently associated with all-cause mortality in nonischemic heart failure with reduced ejection fraction when adjusted for estimated glomerular filtration rate, hemoglobin, N-terminal pro-brain natriuretic peptide, body mass index, and left atrial diameter (hazard ratio: 1.012, 95% confidence interval: 1.003-1.020, P = 0.005). The high-sensitivity troponin T cut-off value was 21.5 ng/L to predict a worse prognosis in nonischemic heart failure with reduced ejection fraction. There was an independent association between high-sensitivity troponin T and all-cause mortality.

Prognostic Significance of Statins in Ischemic and Non-ischemic Heart Failure Patients with Reduced Ejection Fraction in Real Life.

Although the positive effects of statin therapy in cardiovascular diseases are known, current heart failure guidelines do not recommend statins. The aim of this study was to investigate the effect of statin on all-cause mortality in patients with ischemic or non-ischemic heart failure with low ejection fraction using real-life data. In this study, 1144 patients with heart failure with low ejection fraction were included retrospectively. In the study cohort, 55.4% were ischemic heart failure patients and 42.4% of the patients were on statin therapy. The rate of patients using statins was 60.5% in the ischemic group and 20.2% in the non-ischemic group (P <.001). During the median 35-month follow-up, 337 deaths were observed. Mortality rates were similar in ischemic and non-ischemic groups (31.3% vs 26.9%, P =.092). When the statin usage status of the patients was examined, ischemic heart failure, all survivors, and survivors with ischemic heart failure were using statins at a higher rate (P <.001). In the Kaplan-Meier analysis of all patients, the mortality rate was 22.7% in statin users, while the mortality rate was significantly higher in those who did not use statins, 34.4% (P <001). All-cause mortality was significantly higher in patients with ischemic heart failure not using statins than in patients using statins (P <.001) but not in non-ischemic heart failure (P =.07). Using statin was an independent predictor of all-cause mortality in all patients (hazard ratio: 0.661, 95% CI: 0.518-0.843, P =.001) and ischemic heart failure patients (hazard ratio: 0.618, 95% CI: 0.456-0.838, P =.002). Since statin use reduces all-cause mortality in patients with ischemic heart failure, it may be recommended to continue statin therapy.

Plasma zonulin correlates with cardiac dysfunction and poor physical performance in patients with chronic heart failure

AimsAn aberrant intestinal permeability is often associated with systemic inflammation and cardiovascular diseases accompanied by compromised physical performance. However, the link between these complications is poorly defined. Here we investigated the potential association of zonulin, a regulator of intestinal permeability, with ischemic and non-ischemic heart failure (HF) and, associated physical disability. Main methodsThe investigation including echocardiography, short physical performance battery (SPPB) and measurement of plasma zonulin and c-reactive protein (CRP), was performed in 59 HF patients and an equal number of healthy controls. Key findingsAs expected, the left ventricular end-systolic dimension (LVESD) was significantly higher, which was accompanied by a significantly lower LV ejection fraction (EF) in the HF patients compared to controls. The levels of plasma zonulin and CRP was profoundly elevated in both ischemic (P < 0.0001) and non-ischemic (P < 0.01) HF patients. Interestingly, LVESD positively (r2 = 0.156, P = 0.001) and LVEF negatively (r2 = 0.186, P = 0.0006) correlated with the level of zonulin in HF patients. The SPPB scores for balance, chair sit-to-stand (STS), gait speed (GS), and hand grip strength (HGS) were consistently compromised in HF patients. Moreover, LVESD was negatively (r2 = 0.118, P = 0.007), and there was trend of positive correlation of LVEF (r2 = 0.05, P = 0.08) with the SPPB scores for balance. Consistently, zonulin levels was negatively correlated with SPPB scores for balance (r2 = 0.176, P = 0.0009), STS (r2 = 0.120, P = 0.001) and HGS (r2 = 0.085, P = 0.02). SignificanceChronic cardiac complications induce the level of plasma zonulin, which predicts the cardiac remodeling and dysfunction and physical performance in patients with chronic HF.

Cd4+ T cell phenotypes, autoantibodies and transcriptional signatures overlap between myocarditis, ischemic and nonischemic heart failure, suggesting shared inflammatory pathogenic mechanisms

Abstract Background Myocarditis may progress to heart failure (HF) often as a result of viral myocardial infection where cardiomyocyte damage exposes sequestered self-antigens including cardiac myosin (CM) leading to autoimmunity. CM acts as an adjuvant via activation of Toll-like receptor (TLR)2 and TLR8, and is a potent autoantigen promoting HF in myocarditis through elevated IL-6, IL-17A and Th17 differentiation concomitant with autoantibody responses against CM. Since cardiomyocyte damage also occurs in ischemic and nonischemic cardiomyopathies, we investigated the hypothesis that ischemic and nonischemic HF would have similar inflammatory phenotypes. Purpose We defined CD4+ T helper cell phenotypes, autoantibodies, and peripheral blood transcriptome of the inflammatory phenotypes in myocarditis, compared to ischemic, and nonischemic HF. The identification of immune phenotypes in myocarditis and HF are important for consideration of inflammatory interventions and immunotherapies in myocarditis and HF. Methods Peripheral blood was collected from myocarditis patients within 6 months of disease onset, and from clinically stable, chronic HF patients. CD4+ T helper cells (Th1, Th2, and Th17) were evaluated by flow cytometry after density gradient separation, and human CM autoantibody titers were determined by ELISA. Whole blood RNA sequencing, Ingenuity Pathway Analysis (IPA), as well as multi-contrast pathway enrichment were performed. Results (Fig. 1A) Significantly elevated human CM autoantibodies were observed in myocarditis, ischemic and nonischemic HF patients, and correlated with nonrecovered patients and poor outcomes. (Fig. 1B) Myocarditis and nonischemic HF patients had significantly elevated Th17 and Th2 frequencies. Ischemic HF patients had a trend toward elevated Th 17 and Th 2 CD4+ T cell frequencies. None of the cohorts demonstrated an elevation in Th1 (not shown) (Fig 2A), IPA canonical pathway enrichment for all cohorts together showed elevated pathways concordant with our proposed pathogenic mechanisms in myocarditis and HF, including TLR and inflammasome signaling and IL17A and IL13 pathways (Fig. 2B). Myocarditis and nonischemic HF shared more inflammatory pathway enrichment in common than ischemic HF (Fig. 2C) Multi contrast pathway enrichment demonstrated that males in each cohort shared TLR and IL1b signaling that was not observed in females. Conclusion Nonischemic HF patients have overlapping immunological features with myocarditis including elevated anti-CM autoantibodies, as well as Th17, and Th2 frequencies. Ischemic HF demonstrated elevated CM autoantibodies and fewer inflammatory genes and pathways. The transcriptome supported the immune phenotypes in myocarditis and heart failure suggesting pathogenic autoimmune and inflammatory mechanisms shared in myocarditis and ischemic HF. The results have implications for immunomodulatory therapies in myocarditis and HF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health

Associations of GPCR autoantibodies with clinical, histological, metabolic and hemodynamic features in non-ischemic heart failure patients

Abstract Background Roughly one third of cases of chronic heart failure (HF) are caused by genetic predisposition, metabolic stress and cardiac inflammation. Animal studies suggest that heart-reactive autoantibodies, most notably those directed against G-protein-coupled receptors (GPCR), could also play a pathogenetic role in the disease. However, so far, a causal link between humoral GPCR-autoimmunity and human non-ischemic heart failure other than Chagas' cardiomyopathy remains unclear. Purpose Here, we investigated possible associations of GPCR autoantibodies with inflammatory, hemodynamic, metabolic and functional parameters in patients with chronic non-ischemic HF unrelated to Chagas' disease. Methods We prospectively included 95 patients with newly diagnosed non-ischemic heart failure of unknown origin. Basic cardiac characterization comprised transthoracic echocardiography, cardiac magnetic resonance imaging, coronary angiography and right heart catheterization with endomyocardial biopsy. Mitochondrial oxidative phosphorylation capacity and coupling was measured using high-resolution respirometry in permeabilized myocardial fibers. A panel of candidate GPCR-autoantibodies was determined by validated and certified immune-assays in peripheral venous blood of the HF-patients and 60 matched healthy individuals. Results were normalized to total IgG. Results Among 10 candidate GPCR-autoantibodies determined, only autoantibodies for α1-adrenergic receptor (α1AR), β1-adrenergic receptor (β1AR), muscarinic receptor M5 (M5AR), angiotensin II receptor type 1 (AT1R) and type 2 (AT2R) exhibited HF-associated alterations: Autoantibodies against β1AR, M5R and AT2R were increased. Autoantibodies against α1AR and AT1R were decreased (Figure). These alterations were significant (p&amp;lt;0.01), but not, or only weakly, correlated with markers of cardiac inflammation, cardiac damage, hemodynamics, endomyocardial histology or left ventricular inflammation judged by T2-mapping. However, in HF-patients, increased AT2R autoantibodies were associated with improved myocardial mitochondrial coupling (r=−0.27, p=0.021), and decreased AT2R autoantibodies were associated with insulin resistance (r=−0.24 p=0.027). Conclusion(s) Some previously postulated alterations of GPCR autoantibodies were confirmed in thoroughly characterized HF-patients. However, association of these alterations with cardiac function was not traceable, which argues against a specific pathogenic role. Our data are compatible with multifaceted interactions of GPCR-autoantibodies with the myocardium and potentially with glucose metabolism, possibly indicating a disease-modifying or compensatory role. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Research comission of the Heinrich-Heine University Duesseldorf

Response and long-term outcomes with resynchronization therapy: the role of heart failure etiology

Abstract Background Resynchronization therapy (CRT) reduces mortality across all etiologies of heart failure (HF). Reverse left ventricular (LV) remodelling has been reported to occur more often in non-ischemic patients. Purpose To compare response and outcomes after CRT in non-ischemic (NIHF) and ischemic (IHF) HF patients. Methods Single-center retrospective study of consecutive patients submitted to CRT implantation (2007–2018). Major adverse cardiac events (MACE) included HF hospitalization or all-cause mortality (ACM). Clinical response was defined as New York Heart Association (NYHA) class improvement without MACE in the 1st year of follow-up (FU). Echocardiographic (echo) response implied left ventricle end-systolic volume reduction of &amp;gt;15% at 1-year. LV ejection fraction [LVEF] ≥50% during 1st year of FU defined superresponse. Survival analysis with Kaplan-Meier method and Log-rank test was performed to compare outcomes. Multivariate analysis was performed to assess if HF etiology predicted response to CRT. Results 295 patients (mean age 67±11 years, 91.5% left bundle branch block, baseline QRS 171±22 ms) were included. Patients in NIHF group (n=208, 72.5%) were more often female (35.6% vs 15.6%, p&amp;lt;0.001), tended to be younger (67 vs 70 years, p=0.05), had more valve disease (36.7% vs 23.6%, p=0.037) and kidney disease (32.9% vs 18.5%, p=0.015). In NIHF patients, right ventricular dysfunction (tricuspid annular plane systolic excursion &amp;lt;17 mm) was less common (25.6% vs 47.1%, p=0.039). Addition of defibrillator was identical (53.8% vs 55.7%, p=0.882). NYHA class improvement (79.4% vs 78.4%, p=0.987) and echo response (71.2% vs 74.4%, p=0.860) were similar. NIHF patients were more often superresponders (25.7% vs 9.5%, p=0.006), with greater improvement in LVEF (Δ 11.6% vs 7.6%, p&amp;lt;0.001). Clinical response was more frequent in NIHF patients (66.3% vs 50.6%, p=0.023). After multivariate analysis, HF etiology was not predictive of clinical (p=0.960) or echo response (p=0.075). During a mean FU of 3.8 years, occurrence of MACE (Log rank test, p&amp;lt;0.001) and ACM (Log rank test, p&amp;lt;0.001) were lower in NIHF [Figure 1]. Ventricular arrythmias (6.4% vs 7.5%, p=0.993) or appropriate defibrillator therapies (5.3% vs 7.5%, p=0.743) did not differ. Conclusions In this cohort, consisting mostly of patients with LBBB and QRS ≥150 ms, HF etiology did not predict clinical or echo response to CRT. Still, NIHF patients showed a greater extent of LV remodelling. Lower MACE and ACM rates were also observed in non-ischemic patients. Funding Acknowledgement Type of funding sources: None.

Reintroducing dyssynchrony significantly increases myocardial stiffness at mitral valve closure

Abstract Background Cardiac shear wave elastography (SWE) allows for the non-invasive assessment of myocardial stiffness via the detection of shear waves. Shear waves are mechanical waves that travel through the heart after for example mitral valve closure (MVC). The propagation speed of these waves is directly dependent on myocardial stiffness, where a higher shear wave speed correlates with a higher stiffness. However, the effect of a left bundle branch block (LBBB) and a dyssynchronous contraction pattern on shear wave speed is currently unknown. Purpose To investigate the effect of a dyssynchronous contraction pattern caused by LBBB on shear wave speed. Methods We included 29 non-ischemic heart failure patients with an LBBB (68±15y; 52% males) and 9 age-matched healthy volunteers (68±4y; 55% males) as controls. All LBBB patients were implanted with a CRT device and dyssynchrony was reintroduced by turning biventricular (BiV) pacing off to allow native ventricular conduction. Echocardiographic images were taken during BiV pacing on and BiV pacing off, with a conventional ultrasound machine and an experimental high frame rate ultrasound scanner. Shear waves were visualized in M-modes of the septum, colour coded for tissue acceleration. The slope of the shear waves in the M-mode represents their propagation speed. Further, longitudinal strain at MVC and the time difference between onset of septal contraction and MVC were measured (negative time values indicate that MVC occurs before onset of septal contraction). Results There was no significant difference in shear wave speed between healthy controls and LBBB patients during BiV pacing on (4.5±1.1 m/s vs 4.9±1.2 m/s; p=0.365; Figure A). However, shear wave speed was significantly higher in LBBB patients during BiV pacing off compared to healthy controls (4.5±1.1 m/s vs 5.6±1.1 m/s; p=0.041; Figure A). Turning BiV pacing off lead to a significant increase in shear wave speed in LBBB patients (4.9±1.2 m/s vs 5.6±1.1 m/s; p=0.003; Figure A), indicating that the reintroduction of LBBB increases septal myocardial stiffness. MVC occurred significantly later after the onset of septal contraction during BiV pacing off (−9±57 ms vs 40±26 ms; p=0.001) and strain values at MVC were more negative (−0.3±0.6% vs −2.0±1.5%; p&amp;lt;0.001). Therefore we hypothesize that during BiV pacing off, the septal wall was further into the contraction phase at the time of MVC, leading to an increased myocardial stiffness, and thus increased shear wave speed (Figure B). Our interpretation was further strengthened by a strong correlation between the change in shear wave speed and the change in septal longitudinal strain at MVC when BiV pacing is turned off (r=0.81; p&amp;lt;0.001; Figure C). Conclusion Reintroducing dyssynchrony in LBBB patients significantly increases shear wave speed at MVC. Our results suggest that the earlier contraction of the septum during dyssynchrony is an explanation for the higher septal stiffness at MVC. Funding Acknowledgement Type of funding sources: None.

Validation of R-hf risk score for risk stratification in ischemic heart failure patients: A prospective cohort study

BackgroundThe aim of this study was to validate R-heart failure (R-hf) risk score in ischemic heart failure patients. MethodsWe prospectively recruited a cohort of 179 ischemic and 107 non-ischemic heart failure patients. This study mainly focused on ischemic heart failure patients. Non-ischemic heart failure patients were included for the purpose of validation of the risk score in various heart failure groups. Patients were stratified in high risk, moderate risk and low risk groups according to R-hf risk score. ResultsA total of 179 participants with ischemic heart failure were included. Based on R-hf risk score, 82 had high risk, 50 had moderate risk and 47 had low risk heart failure scores. More than half of the patients having R-hf score of <5 had renal failure (n = 91, 50.8%) and anemia (n = 99, 55.3%). Notably, HFrEF was more prevalent in patients with high risk score (74, 90.2%). Patients with high risk score had significantly higher creatinine (2.63 ± 1.96, p < 0.001), Troponin-T HS (59.9 ± 38.0, p < 0.001) and PRO BNP (17842 ± 6684, p < 0.001) when compared to patients with low and moderate risk score. Patients with low risk score had significantly higher Hb (13.2 ± 1.85, p < 0.001), Albumin (3.69 ± 0.42, p < 0.001) and GFR (90.0 ± 8.04, p < 0.001). A R-hf score of <5 was a significant predictor of mortality in ischemic (OR = 50.34; 95% CI [16.94–194.00, p < 0.001) and non-ischemic (OR = 46.34; 95% CI [12.97–225.39], p < 0.001) heart failure patients. ConclusionsLower R-hf risk score is a significant predictor of mortality in ischemic and non-ischemic heart failure patients. Risk score can be accessed at https://www.hfriskcalc.in.

The value of cardiac sympathetic activity and mechanical dyssynchrony as cardiac resynchronization therapy response predictors: comparison between patients with ischemic and non-ischemic heart failure

BackgroundImpaired cardiac sympathetic activity and mechanical dyssynchrony (MD) are associated with poor prognosis in patients with heart failure (HF) after cardiac resynchronization therapy (CRT). The study aims to assess the significance of scintigraphic evaluation of cardiac sympathetic innervation and contractility in predicting response to CRT in patients with ischemic and non-ischemic chronic HF. Methods and resultsThe study includes 58 HF patients, who were referred for CRT. Prior to CRT all patients underwent 123I-metaiodobenzylguanidine (123I-MIBG) imaging and gated myocardial perfusion imaging (MPI) using a cadmium-zinc-telluride (CZT) SPECT/CT device. At a one-year follow-up post-CRT, the delayed heart-to-mediastinum 123I-MIBG uptake ratio was an independent predictor of CRT response in non-ischemic HF patients (OR 1.469; 95% CI 1.076-2.007, p = .003). In ischemic HF patients the MD index histogram bandwidth (HBW) obtained by CZT-gated MPI had a predictive value (OR 1.06, 95% CI 1.001-1.112, p = .005) to CRT response. ConclusionCRT response can be predicted by cardiac 123I-MIBG scintigraphy, specifically by the heart-to-mediastinum ratio in non-ischemic HF and by the MD index HBW in ischemic HF. These results suggest the value of a potentially useful algorithm to improve outcomes in HF patients who are candidates for CRT.

Prognostic value of high-sensitivity cardiac troponin I in patients with non-ischaemic heart failure: insights from China.

Evidence of the prognostic value of high-sensitivity troponin in patients with non-ischaemic heart failure (NIHF) is scarce. This study aimed to assess the predictive value of high-sensitivity cardiac troponin I (hs-cTnI) in NIHF patients. Hs-cTnI was measured at baseline in 650 NIHF patients admitted to the Heart Failure Center. The prognostic value of hs-cTnI was assessed based on a well-established model (including age, sex, New York Heart Association class, left ventricular ejection fraction, haemoglobin, sodium, estimated glomerular filtration rate, diabetes mellitus, treatment with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, treatment with β-blockers, and NT-proBNP). During a median follow-up of 1036days, 163 patients died of various causes. In total, 46.92% of patients had high hs-cTnI (hs-cTnI >0.011ng/ml). Over a 3-year follow-up, patients with high hs-cTnI (>0.011ng/ml) had a 1.54 [95% confidence interval (95% CI) 1.11-2.15] fold higher all-cause mortality risk than those without. Increasing concertation of hs-cTnI was also associated with a 23.0% (95% CI 13-33%, per log2 increase) increment risk of all-cause mortality. The inclusion of hs-cTnI significantly improved the risk prediction and stratification of all-cause mortality (integrated discrimination improvement 1.58%, 95% CI 0.38-2.79%, absolute net reclassification improvement 23.41% 95% CI 4.52-44.49%, additive net reclassification improvement 27.8%, 95% CI 9.29-46.3%) of the well-established model. Hs-cTnI provides significant prognostic value and could further remarkably improve risk stratification and prediction capabilities in NIHF patients.

Evaluation of Sleep Quality with Use of Angiotensin Receptor Neprilysin Inhibitor in Patients with Reduced Ejection Fraction Heart Failure

Background and Aim: It is known that chronic heart failure reduces sleep quality by causing sleep problems. In recent years, it has been observed that sacubitril-valsartan, which is an angiotensin receptor neprilysin inhibitor, reduces mortality and hospitalization in patients with heart failure. The aim of our study is to examine whether sacubitril-valsartan affects sleep quality in patients with reduced ejection fraction heart failure apart from these benefits.&#x0D; Material and Method: In our study, 44 patients with a history of heart failure with reduced ejection fraction applied to our cardiology outpatient clinic of Gazi Yaşargil Training and Research Hospital were included. Demographic, clinical, laboratory, electrocardiographic, and echocardiographic parameters of these patients were examined. Sacubitril-valsartan treatment was initiated in all patients. Dose titration was performed in patients who could tolerate the treatment. Pittsburgh sleep quality index questionnaire was performed in all patients before treatment and at the end of the second month.&#x0D; Result: The median age of the study population was 61.5 (47.2 - 70.7, IQR) years and 30 (68.2 %) of them were male. There were 30 (72.7 %) ischemic heart failure patients and 14 (27.3 %) non-ischemic heart failure patients. There was a significant decrease in the number of patients with poor sleep quality after angiotensin receptor neprilysin inhibitor treatment compared to baseline [36 (81.8 %) vs 30 (68.2 %), p= 0.031]. In addition, there was a significant decrease in the total Pittsburgh sleep quality index score of patients compared to the baseline [9.0 (7.0 - 12.0) vs 7.0 (5.0 - 9.0), p &lt; 0.001].&#x0D; Conclusion: In our study, we observed that sacubitril-valsartan treatment improves sleep quality in patients with reduced ejection fraction heart failure.