Citations

AbstractObjectiveTo describe the hemodynamic and early clinical outcomes of percutaneous alcohol septal ablation in patients with concomitant dynamic left ventricular outflow tract (LVOT) obstruction and aortic valvular stenosis (AS).BackgroundAlcohol septal ablation is an established method to relieve dynamic LVOT obstruction in patients with hypertrophic cardiomyopathy (HCM). However, the feasibility, safety, and efficacy of alcohol septal ablation in patients with serial obstructions from HCM and AS remain unclear.MethodsIn this case series, we describe the early outcomes of alcohol septal ablation in six patients with significant dynamic LVOT obstruction and AS. All patients had evidence of severe dynamic LVOT obstruction (resting or provoked gradient ≥50 mmHg), mild to severe AS, and NYHA class III symptoms or greater.ResultsFour (66.7%) patients had septal ablation performed in the setting of concomitant native valvular AS and two (33.3%) patients had TAVR performed prior to septal ablation. Successful alcohol septal ablation was performed in all patients and was associated with an immediate reduction of the dynamic LVOT gradient with a residual fixed obstruction related to AS. Four (66.7%) patients had follow‐up at 1 month and of these, three (75%) had NYHA Class I–II symptoms and one (25%) Class III.ConclusionsAlcohol septal ablation is a feasible method of relieving dynamic LVOT obstruction in patients with concomitant HCM and AS. Further study is required to determine the optimal treatment approach in these patients.

Abstract Aims Pulmonary hypertension (PH) represents an important phenotype among the broader spectrum of patients with heart failure with preserved ejection fraction (HFpEF), but its mechanistic basis remains unclear. We hypothesized that activation of endothelin and adrenomedullin, two counterregulatory pathways important in the pathophysiology of PH, would be greater in HFpEF patients with worsening PH, and would correlate with the severity of haemodynamic derangements and limitations in aerobic capacity and cardiopulmonary reserve. Methods and results Plasma levels of C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM), central haemodynamics, echocardiography, and oxygen consumption (VO2) were measured at rest and during exercise in subjects with invasively-verified HFpEF (n = 38) and controls free of HF (n = 20) as part of a prospective study. Plasma levels of CT-proET-1 and MR-proADM were highly correlated with one another (r = 0.89, P < 0.0001), and compared to controls, subjects with HFpEF displayed higher levels of each neurohormone at rest and during exercise. C-terminal pro-endothelin-1 and MR-proADM levels were strongly correlated with mean pulmonary artery (PA) pressure (r = 0.73 and 0.65, both P < 0.0001) and pulmonary capillary wedge pressure (r = 0.67 and r = 0.62, both P < 0.0001) and inversely correlated with PA compliance (r = −0.52 and −0.43, both P < 0.001). As compared to controls, subjects with HFpEF displayed right ventricular (RV) reserve limitation, evidenced by less increases in RV s′ and e′ tissue velocities, during exercise. Baseline CT-proET-1 and MR-proADM levels were correlated with worse RV diastolic reserve (ΔRV e′, r = −0.59 and −0.67, both P < 0.001), reduced cardiac output responses to exercise (r = −0.59 and −0.61, both P < 0.0001), and more severely impaired peak VO2 (r = −0.60 and −0.67, both P < 0.0001). Conclusion Subjects with HFpEF display activation of the endothelin and adrenomedullin neurohormonal pathways, the magnitude of which is associated with pulmonary haemodynamic derangements, limitations in RV functional reserve, reduced cardiac output, and more profoundly impaired exercise capacity in HFpEF. Further study is required to evaluate for causal relationships and determine if therapies targeting these counterregulatory pathways can improve outcomes in patients with the HFpEF-PH phenotype. Clinical trial registration NCT01418248; https://clinicaltrials.gov/ct2/results? term=NCT01418248&Search=Search

Background Neprilysin is a metalloprotease involved in proteolysis of numerous peptides, including natriuretic peptides, and is of prognostic and therapeutic importance in heart failure with reduced ejection fraction. No studies have investigated circulating neprilysin in the community, its clinical correlates, or its relationship to cardiovascular disease in the general population. Methods and Results Plasma neprilysin was measured in 1536 participants from Olmsted County, Minnesota, using a commercially available sandwich ELISA assay. Clinical and echocardiographic correlates and subsequent outcomes were determined. Soluble neprilysin is non‐normally distributed in the community (median: 3.9 ng/mL; interquartile range: 1.0–43.0 ng/mL). There was no relationship between plasma neprilysin and age (Spearman correlation: −0.04, P =0.16); body mass index (Spearman correlation: −0.04, P =0.16); glomerular filtration rate (Spearman correlation: −0.007, P =0.8); or A‐, B‐, or C‐type natriuretic peptides (Spearman correlation: 0.03, P =0.22; −0.001, P =0.96; 0.01, P =0.67, respectively). Among tertiles of neprilysin, the lowest tertile group had the highest prevalence of smokers ( P <0.001), hypertension ( P =0.04), dyslipidemia ( P =0.03), and diastolic dysfunction ( P =0.02). Soluble neprilysin was not prospectively associated with death or heart failure over a median of 10.7 years. Conclusions In a large community‐based cohort, for the first time, we described the distribution of circulating neprilysin in the general community. We observed that neprilysin does not correlate with natriuretic peptide levels and is not independently associated with adverse outcomes. The novel associations observed between low soluble neprilysin levels and an adverse cardiometabolic and smoking profile requires further investigation.

Objective This study aimed to identify characteristics, spectrum of tricuspid regurgitation (TR) severity and treatment patterns in patients considered for intervention of severe TR at a tertiary centre. The population being considered for TR intervention is currently not well defined and the role of transcatheter interventions is unclear. Methods The study involved 87 patients with severe TR considered for intervention from 1 March 2016 to 12 November 2018 at Mayo Clinic. Patients receiving medications alone were compared with those receiving intervention to identify patterns in demographics, clinical/echocardiographic associations and survival. Results Mean age was 80±9 (56% female), 93% had atrial fibrillation and 64% had chronic kidney disease ≥3 a. Follow-up was 331±276 days; 95% were symptomatic with 6 min walk distance of 270±110 m. Loop diuretics were used in 93%; aldosterone antagonists in 35%. Mean tricuspid annular plane systolic excursion was 15.6±3.8 mm, effective regurgitant orifice area (EROA) 82±32 mm2 and stroke volume index 39±11 mL/m2; 48% had at least moderate right ventricular (RV) dysfunction, and 75% did not undergo intervention. Patients receiving intervention showed trends towards larger EROA (93±33 vs 75±31 mm2), better right ventricular function and more severe symptoms. Overall group 30-day and 1-year survival were 100% and 76%, respectively. Conclusions Patients with severe TR considered for intervention are commonly elderly with atrial fibrillation, advanced TR and RV dysfunction; 75% were treated with medications alone and not offered intervention. Patients with greater EROA, better RV function and more severe symptoms were more likely to receive intervention. These findings have implications for future trial design.

Abstract Despite improvements in outcomes in the last few decades for heart failure (HF) with reduced ejection fraction (HFrEF), there still remains a need for novel therapies as many patients incompletely recover with existing therapies and progress to advanced HF. In this review, we will discuss recent advances in the management of HFrEF with a focus on upcoming therapies that hold the greatest promise for clinical use. We will discuss novel pharmacological therapies and areas of uncertainty with existing therapies. We will also discuss the potential utility and controversy surrounding novel interventions for HF such as percutaneous mitral valve repair, atrial fibrillation ablation, and other emerging interventions with positive signals for benefit in HFrEF. Finally, we will summarize the current state of stem cell and gene therapy for HFrEF and future directions.