Vagal Neuromodulation in Chronic Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta-Analysis

Objectives: The aim of this study was to evaluate the effects of invasive vagal nerve stimulation (VNS) in patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF).Background: Heart failure is characterized by autonomic nervous system imbalance and electrical events that can lead to sudden death. The effects of parasympathetic (vagal) stimulation in patients with HF are not well-established.Methods: From May 1994 to July 2020, a systematic review was performed using PubMed, Embase, and Cochrane Library for clinical trials, comparing VNS with medical therapy for the management of chronic HFrEF (EF ≤ 40%). A meta-analysis of several outcomes and adverse effects was completed, and GRADE was used to assess the level of evidence.Results: Four randomized controlled trials (RCT) and three prospective studies, totalizing 1,263 patients were identified; 756 treated with VNS and 507 with medical therapy. RCT data were included in the meta-analysis (fixed-effect distribution). Adverse effects related to VNS were observed in only 11% of patients. VNS was associated with significant improvement (GRADE = High) in the New York Heart Association (NYHA) functional class (OR, 2.72, 95% CI: 2.07–3.57, p < 0.0001), quality of life (MD −14.18, 95% CI: −18.09 to −10.28, p < 0.0001), a 6-min walk test (MD, 55.46, 95% CI: 39.11–71.81, p < 0.0001) and NT-proBNP levels (MD −144.25, 95% CI: −238.31 to −50.18, p = 0.003). There was no difference in mortality (OR, 1.24; 95% CI: 0.82–1.89, p = 0.43).Conclusions: A high grade of evidence demonstrated that vagal nerve stimulation improves NYHA functional class, a 6-min walk test, quality of life, and NT-proBNP levels in patients with chronic HFrEF, with no differences in mortality.

Correlates and short-term prognostic value of plasma n-terminal pro-brain natriuretic peptide levels among heart failure patients: A prospective cohort study

BackgroundStudies conducted in developed countries have found measurements of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) to be important in evaluating heart failure (HF) prognosis, however this has not yet been studied in sub-Saharan Africa. The aim of this study was to determine clinical correlates and short-term prognostic value of plasma NT-proBNP levels among HF patients.MethodologyThis was a hospital-based prospective cohort study conducted at Jakaya Kikwete Cardiac Institute, Tanzania from June to December 2020. Patients were consecutively enrolled when they fulfilled the inclusion criteria. Clinical details and NT-proBNP levels were measured at baseline and at 30-day follow-up. Pearson's chi square test was used to associate New York Heart Association (NYHA) functional class and NT-proBNP levels, while Spearman’s correlation coefficient was used to correlate between left ventricular ejection fraction (LVEF) and NT-proBNP levels. Receiver Operating Characteristic (ROC) curves were drawn to determine the best prognostic cut off points of NT-proBNP levels for the different clinical outcomes. A P-value of <0.05 was considered statically significant.Results155 HF patients were enrolled. Their mean±SD age was 48±16 years, 52.3% were male and their mean ±SD LVEF was 37.3±10.7%. At baseline, the median (IQR) NT-proBNP levels was 7654pg/ml (2289, 16000), and the levels dropped to 3383pg/ml (731, 9785) after 1 month. Baseline plasma levels of NT-proBNP increased as the NYHA functional class worsened, (P = 0.018), and with decreasing LVEF (r = -0.65, p<0.05). The ROC curve identified an overall cut-off point for poor prognosis at 18000pg/ml with 54.4% sensitivity and 93.7% specificity (area under the curve (AUC): 0.8). The NT-proBNP cut-off point for mortality was 24500 pg/ml with 100% sensitivity and specificity of 92.54% (AUC: 0.958). The ROC analysis also identified levels of NT-proBNP of ≥7899pg/ml to predict re-hospitalization, with 76% sensitivity and 60% specificity (AUC: 0.68), while levels ≥18762.1 pg/ml predicted long hospital stay with a sensitivity of 100% and specificity of 85.62% (AUC: 0.939).ConclusionThese results demonstrate that NT-proBNP is a powerful measure to predict readmission, mortality and long hospital stay in HF patients and can facilitate discussions with patient prognosis, decisions regarding interventions, and continuity of care.

Head-to-head comparison of NT-proBNP and soluble ST2 for long-term prognosis of patients with hypertrophic cardiomyopathy

Background N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure (HF) in hypertrophic cardiomyopathy (HCM), however, evidence regarding soluble interleukin-1 receptor-like 1 (ST2) in this population is lacking. Purpose To assess the ST2 and NT-proBNP significance for risk stratification of patients with HCM during long-term follow-up. Methods We prospectively enrolled a cohort of consecutive patients with HCM admitted to an ambulatory HF Unit in a Tertiary University Hospital. All patients had clinical and echocardiographic evaluation and measurement of NT-proBNP and ST2 at inclusion. The primary endpoint was the composite of all-cause death or HF-related hospitalization. Results 103 patients were enrolled, 68% (n=70) males with a median (IQR) age of 60 (50–71) years. The median (IQR) of ST2 was 31.5 (IQR: 24.5 – 40.7) pg/mL. During a median follow-up of 2.5 years, 17 patients had the primary endpoint. Both, NT-proBNP and ST2 (both log-transformed) were associated with the primary endpoint in the univariable analyses (p&lt;0.01). However, after adjustment by age, sex, NYHA functional class and left ventricular ejection fraction (LVEF), this association remained statistically significant only for ST2 (HR: 4.62, 95% CI 1.80–11.87, p=0.001 vs HR: 1.57, 95% CI 0.97–2.54, p=0.068 for NT-proBNP). The addition of ST2 to a clinical model (age, sex, NYHA functional class and LVEF) increased the Harrel's C statistic from 0.70 to 0.76, while the addition of NT-proBNP increase this C-statistic only to 0.73. Conclusions ST2 appears to be a valuable biomarker for the prediction of death and heart failure related hospitalization in patients with HCM, outperforming the prognostic value of NT-proBNP. Future research should delve into this association. FUNDunding Acknowledgement Type of funding sources: None.

Long term outcomes of patients with aortic structural valve deterioration treated with transcatheter valve in valve implantation

Introduction The Valve-in-Valve (ViV) technique is an established alternative for the treatment of structural bioprosthetic valve deterioration (SVD). Data describing the long term follow up of patients treated with this approach is scarce. We report on our long-term follow up outcomes of patients with SVD in the Aortic position treated with ViV. Methods Included were patients with symptomatic SVD in the aortic position valve who were treated by Valve in valve transcatheter aortic valve implantation (ViV-TAVI) during the years 20102019 in our center. Three main outcomes were examined during follow up: NYHA functional class, hemodynamic of the VIV-TAVI per echocardiography, and overall mortality. Results Our cohort consisted of 84 patients (mean age 78.8±8.9 years). The indications for aortic ViV were: SVD isolated aortic stenosis in 37.6%, SVD isolated aortic regurgitation in 42.2% and combined valve pathology in 20.0%. Self-expandable and balloon-expandable devices were used in 73 (85.9%) and 12 (14.1%), respectively. Average time of follow up was 3.74±2.4 years. 95% and 91% of patients were in NYHA functional class I/II at 1 and 5 year follow up respectively. At one year the mean trans-aortic valve pressure was 15.3±9.3 and rates of ≥ moderate aortic regurgitation were 3.7%. Survival was 91.4% (95% CI 85.6–97.7) at one year and 79.5% (95% CI 70.2–90.0) at 3 years. Conclusion ViV in the aortic position offers an effective and durable treatment option for patient with SVD, with low rates of all-cause mortality, excellent hemodynamic and improved functional capacity at 3 years follow up. FUNDunding Acknowledgement Type of funding sources: None. NYHA functional class over follow up

New foundational therapy in heart failure with reduced ejection fraction: should we keep following the 2016 European Society of Cardiology Heart Failure Guideline in 2021?

Introduction The 2016 European Society of Cardiology Heart Failure Guidelines (2016 HF GL) suggest sequential therapy initiation with angiotensinogen converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), beta-blocker (BB) and mineralocorticoid receptor antagonist (MRA) for patients with heart failure with reduced ejection fraction (HFrEF). Since their publication, major trials established the benefit of sacubitril/valsartan (ARNi) and SGLT2 in HFrEF, and ARNi are suggested to replace ACEi/ARB as first line therapy. So, with HFrEF foundational therapy evolvement, the 2016 HF GL sequential therapy initiation algorithm has been raised into question. Purpose To compare in the real-world practice, the effect on all-cause mortality of the simultaneous use of every pharmacological class currently included in the HFrEF foundational therapy with conventional sequential therapy. Methods A population of consecutive patients (pts) included in a post-discharge structured follow-up programin in a tertiary center was analyzed. Two groups were defined: 1) patients medicated with all pharmacological classes considered the HFrEF foundational therapy (ARNi, BB, MRA and SGLT2 inhibitor), independently of the dosages – “FT group”; 2) patients medicated with ACEi/ARB, BB and MRA on maximal tolerated doses – “2016 HF GL group”. Pts under other therapeutical combinations were excluded. The study groups were compared with Chi-square and Mann-Whitney tests. Impact on all-cause mortality was established with Kaplan-Meier survival analysis and multivariate Cox regression after adjustment for age, sex and baseline creatinine, NYHA functional class and LVEF. Results From 2016 to February 2021, a total of 101 pts with HFrEF were included and followed for 25±16 months. 54 pts were included in the FT group and 47 in the 2016 HF GL. The study population (69.3% males, 64.6±11.4 years) were mainly in NYHA functional class II (48%) and III (48%). The most common HF aethiologies were ischemic heart disease (49.5%) and dilated cardiomyopathy (30.7%), median LVEF was 26% and 22% were under CRT. Baseline characteristics were similar between groups, except for diabetes (more common in FT group, 70 vs 22%, p&lt;0.001). All-cause mortality rate during follow-up was significantly different between two groups: 1.9% in FT group and 17% in the HF GL group (p: 0.047) – Figure 1. The implementation of all foundational therapy classes was an independent protective factor for all-cause mortality (HR 0.41; IQR 0.004–0.468; P: 0.010) in multivariate Cox regression. Conclusion This real-world study suggests that conventional sequential therapy suggested by the 2016 HF GL may be less effective on reducing all-cause mortality in HFrEF than simultaneous use of all pharmacological classes that nowadays compose the foundation therapy. These results support the hypothesis of promoting early introduction of all therapy classes followed by a tailored uptitration may be beneficial. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

Inclusion of echocardiographic measure of right ventricular function in the non-invasive French pulmonary arterial hypertension risk stratification method

Background Although preserved right ventricular (RV) function is consistently associated with better survival in pulmonary arterial hypertension (PAH), the French risk assessment method has not yet considered echocardiographic criteria of RV function. Purpose In the present study, we tested the value of tricuspid annular plane systolic excursion (TAPSE) measured by echocardiography for non-invasive PAH risk assessment. Methods We retrospectively studied a cohort of 306 incident PAH patients treated in two French expert centers who underwent follow-up TAPSE measurement from echocardiographic apical 4-chamber view in addition to previously validated invasive and non-invasive risk stratification variables. The primary composite outcome was 3-year lung transplantation free survival after follow-up assessment. Results At re-evaluation, 66% of patients were in NYHA functional class I-II and mean pulmonary arterial pressure, cardiac index, N-Terminal pro brain natriuretic peptide (NTproBNP), and 6-minute walk distance (6MWD) were 40±16 mmHg, 3.5±1.1 L/min/m2, 270 [interquartile range (IQR) 896] ng/L and 401 (IQR 213) meters, respectively. The primary outcome occurred in 58 (19%) patients. In multivariable Cox regression analysis, NYHA functional class I-II (p=0.02), NTproBNP &lt;300 ng/L or BNP &lt;50 ng/L (p=0.02), 6MWD &gt;440m (p=0.049) and TAPSE≥17 mm (p=0.02) were associated with lung transplantation free survival. TAPSE provided similar information over 6MWD when both were used alternatively to stratify PAH patients at low risk (log-rank&lt;0.001); Harrell's c-index 0.73. Conclusion Three dichotomized low-risk criteria (TAPSE, 6MWD and NTproBNP or BNP plasma levels) allow non-invasive risk assessment in PAH. FUNDunding Acknowledgement Type of funding sources: None. 3-years transplant-free survival

Severe mitral regurgitation from Libman–Sacks endocarditis treated with MitraClip: a case report

Background Systemic lupus erythematosus (SLE) valvulopathy can manifest as a spectrum of pathologies and treatment of severe valvular dysfunction thus far has been surgical. However, surgery in patients with SLE is frequently associated with high morbidity and mortality due to the presence of significant co-morbidities. Case summary We report the case of a 41-year-old woman with SLE and anti-phospholipid syndrome with extensive co-morbidities including lupus nephritis, pancytopaenia, cerebrovascular accident, and severe airway obstruction from ipsilateral lung collapse and bronchiectasis. She had severe mitral regurgitation (MR) from Libman–Sacks endocarditis and in recent months developed heart failure with progressive exertional dyspnoea from New York Heart Association (NYHA) functional Class from New York Heart Association (NYHA) functional class II to III. In addition, there was progressive left ventricular dilatation and reduction in left ventricular ejection fraction. In view of the high surgical risk, she underwent transcatheter edge-to-edge repair (TEER) of the mitral valve with the MitraClip system. At 1-month follow-up, she was back to NYHA functional Class II with mild MR. Discussion Our case demonstrates that in select patient with suitable anatomy, TEER is a potential treatment option for severe MR from SLE valvulopathy.

Clinical effects of the enhanced external counterpulsation therapy in patients with ischemic chronic heart failure exacerbation COVID-19

Objectives The aim of the study was to assess the effects of the enhanced external counterpulsation (EECP) therapy as a rehabilitation method in patients with ischemic chronic heart failure (CHF) after COVID-19. Methods 54 (n=54) stable symptomatic CHF (NYHA, functional class I-II; 35%≤LVEF≤50%) subjects (44 male and 10 female; mean age 61±9,8) with prior anamnesis of CAD, at least one myocardial infarction got the exacerbation of CHF after COVID-19 episode. They were randomized in a 2:1 manner into either 35 1-hour 250–300 mm Hg sessions of EECP (n=36; 30 male, 6 female) or Sham-EECP (n=18; 14 male, 4 female). All subjects had been received optimal CHF and CAD drug therapy. At baseline, a month and half a year after EECP course every subject was examined with echocardiography and 6-minute walk test. Results All 36 active EECP treatment group subjects improved by at least 1 NYHA class, 66% of them had no heart failure symptoms post treatment (p&lt;0.01). 84% of treatment group pts. had sustained NYHA class improvement at half a year follow-up (p&lt;0.01), compared with baseline. There was significant difference between LVEF 44±6,5% at baseline vs post-EECP LVEF 50±4,6% (p&lt;0.01) in active EECP treatment group subjects. At the same time there were no significant changes of NYHA class and LVEF in Sham-EECP subjects. No one subject dies after half a year of follow up. Conclusions Enhanced external counterpulsation (EECP) therapy sustainably improves NYHA functional class and LVEF in patients with ischemic CHF exacerbation after COVID-19. FUNDunding Acknowledgement Type of funding sources: None.

5 Year Outcomes of Patients With Aortic Structural Valve Deterioration Treated With Transcatheter Valve in Valve – A Single Center Prospective Registry

The Valve-in-Valve (ViV) technique is an established alternative for the treatment of structural bioprosthetic valve deterioration (SVD). Data describing the intermediate term follow up of patients treated with this approach is scarce. We report on our intermediate-term outcomes of patients with SVD in the Aortic position treated with ViV. Included were patients with symptomatic SVD in the aortic position valve who were treated by Valve in valve transcatheter aortic valve implantation (ViV-TAVI) during the years 2010-2019 in our center. Three main outcomes were examined during the follow up period: NYHA functional class, ViV-TAVI hemodynamic per echocardiography, and mortality. Our cohort consisted of 85 patients (mean age 78.8 ± 8.9 years). The indications for aortic ViV were: SVD isolated aortic stenosis in 37.6%, SVD isolated aortic regurgitation in 42.2% and combined valve pathology in 20.0%. Self-expandable and balloon-expandable devices were used in 73 (85.9%) and 12 (14.1%), respectively. Average follow up was 3.7 ± 2.4 years. 95 and 91% of patients were in NYHA functional class I/II at 1 and 5 year follow up respectively. At one year, the mean trans-aortic valve pressure was 15 ± 9 mmHg and rates of ≥ moderate aortic regurgitation were 3.7%. Mortality at one year was 8.6% (95% CI 2.3–14.4) and 31% (95% CI 16.5–42.5) at 5 years. ViV in the aortic position offers an effective and durable treatment option for patient with SVD, with low rates of all-cause mortality, excellent hemodynamic and improved functional capacity at intermediate follow up.

Impact of Sacubitril/Valsartan on Clinical and Echocardiographic Parameters in Heart Failure Patients With Reduced Ejection Fraction: Data From a Real Life 2-year Follow-Up Study

Heart failure (HF) represents a widespread health problem characterized by high morbidity and mortality. Sacubitril/Valsartan (sac/val) has improved clinical prognosis in patients affected by HF with reduced ejection fraction (HFrEF). The aim of this study was to evaluate the effectiveness and durability of sac/val treatment on the clinical, hemodynamic and echocardiographic parameters, in real-life consecutive HFrEF outpatients, evaluated up to 2-years of follow-up. We collected 300 repeated observations over time in 60 patients suffering of HFrEF and symptomatic despite optimal drug therapy. Patients with left ventricular ejection fraction (LVEF) &lt;35 and II-III NYHA functional class were considered. All patients underwent to clinical-instrumental and laboratory determinations and Minnesota Living with HF Questionnaire (MLHFQ) every 6 months until 24 months to evaluate possible clinical benefits and adverse events. During a 2-year follow-up period and through a 6-monthly control of the study variables both clinical, hemodynamic, biochemical and echocardiographic parameters significantly improved, in particular cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS). Furthermore, there was a reduction of NT-proBNP levels and betterment of renal function and NYHA functional class, demonstrating the efficacy and durability of sac/val treatment. In a multiple linear mixed model the longitudinal evolutions of CI were associated to concomitant changes of GLS and E/e’ ratio. Our study, contemplating the collection of 300 repeated observations in 60 patients, provides a complete and detailed demonstration of sac/val effects, showing effectiveness, safety and effect durability of the treatment every 6 months up to 2-years of follow-up with significant improvement of several clinical, hemodynamic and echocardiographic parameters in HFrEF outpatients.