Impact of Interatrial Shunts on Invasive Hemodynamics and Exercise Tolerance in Patients With Heart Failure

Approximately 50% of patients with heart failure have preserved ejection fraction. Although a wide variety of conditions cause or contribute to heart failure with preserved ejection fraction, elevated left ventricular filling pressures, particularly during exercise, are common to all causes. Acute elevation in left-sided filling pressures promotes lung congestion and symptoms of dyspnea, while chronic elevations often lead to pulmonary vascular remodeling, right heart failure, and increased risk of mortality. Pharmacologic therapies, including neurohormonal modulation and drugs that modify the nitric oxide/cyclic GMP-protein kinase G pathway have thus far been limited in reducing symptoms or improving outcomes in patients with heart failure with preserved ejection fraction. Hence, alternative means of reducing the detrimental rise in left-sided heart pressures are being explored. One proposed method of achieving this is to create an interatrial shunt, thus unloading the left heart at rest and during exercise. Currently available studies have shown 3- to 5-mm Hg decreases of pulmonary capillary wedge pressure during exercise despite increased workload. The mechanisms underlying the hemodynamic changes are just starting to be understood. In this review we summarize results of recent studies aimed at elucidating the potential mechanisms of improved hemodynamics during exercise tolerance following interatrial shunt implantation and the current interatrial shunt devices under investigation

Contribution of cardiac and extra-cardiac disease burden to risk of cardiovascular outcomes varies by ejection fraction in heart failure.

AIMS: Patients with heart failure (HF) often have multiple co-morbidities that contribute to the risk of adverse cardiovascular (CV) and non-CV outcomes. We assessed the relative contribution of cardiac and extra-cardiac disease burden and demographic factors to CV outcomes in HF patients with reduced (HFrEF) or preserved (HFpEF) left ventricular ejection fraction (LVEF). METHODS AND RESULTS: We utilized data from the CHARM trial, which enrolled HF patients across the ejection fraction spectrum. We decomposed the previously validated MAGGIC risk score into cardiac (LVEF, New York Heart Association class, systolic blood pressure, time since HF diagnosis, HF medication use), extra-cardiac (body mass index, creatinine, diabetes mellitus, chronic obstructive pulmonary disease, smoker), and demographic (age, gender) categories, and calculated subscores for each patient representing the burden of each component. Cox proportional hazards models were used to estimate the population attributable risk (PAR) associated with each component to the outcomes of death, CV death, HF, myocardial infarction, and stroke relative to patients with the lowest risk score. PARs for each component were depicted across the spectrum of LVEF. in 2675 chronic HF patients from North America [HFrEF (LVEF ≤40%): n = 1589, HFpEF (LVEF >40%): n = 1086] with data available for calculation of the MAGGIC score, the highest risk of death and CV death was attributed to cardiac burden. This was especially evident in HFrEF patients (PAR: 76% cardiac disease vs. 58% extra-cardiac disease, P < 0.05). Conversely, in HFpEF patients, extra-cardiac burden accounted for a greater proportion of risk for death than cardiac burden (PAR: 15% cardiac disease vs. 49% extra-cardiac disease, P < 0.05). For HF hospitalization, the contribution of both cardiac and extra-cardiac burden was comparable in HFpEF patients (PAR: 42% cardiac disease vs. 53% extra-cardiac disease, P = NS). In addition, demographic burden was especially high in HFpEF patients, with 62% of deaths attributable to demographic characteristics. CONCLUSION: In North American HF patients enrolled in the CHARM trials, the relative contribution of cardiac and extra-cardiac disease burden to CV outcomes and death differed depending on LVEF. The high risk of events attributable to non-cardiac disease burden may help explain why cardiac disease-modifying medication proven to be efficacious in HFrEF patients has not proven beneficial in HFpEF

Uric acid in advanced heart failure: relation to central haemodynamics and outcome

Objective The role of hyperuricaemia as a prognostic maker has been established in chronic heart failure (HF) but limited information on the association between plasma uric acid (UA) levels and central haemodynamic measurements is available.Methods A retrospective study on patients with advanced HF referred for right heart catherisation. Regression analyses were constructed to investigate the association between UA and haemodynamic variables. Cox models were created to investigate if UA was a significant predictor of adverse outcome where log1.1(UA) was used to estimate the effect on outcome associated with a 10% increase in UA levels.Results A total of 228 patients were included (77% males, age 49±12 years, mean left ventricular ejection fraction (LVEF) of 17%±8%). Median UA was 0.48 (0.39–0.61) mmol/L. UA level was associated to pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) in univariable (both p&lt;0.001) and multivariable regression analysis (p&lt;0.004 and p=0.025 for PCWP and CI). When constructing multivariable Cox models including PCWP, CI, central venous pressure, age, estimated glomerular filtration rate (eGFR), use of loop diuretics and LVEF, log1.1(UA) independently predicted the combined endpoint (left ventricular assist device, total artificial heart implantation, heart transplantation or all-cause mortality) (hazard ratio (HR): 1.10 (1.03–1.17), p=0.004) as well as all-cause mortality (HR: 1.15 (1.06–1.25), p=0.001).Conclusions Elevated UA is associated with greater haemodynamic impairment in advanced HF. In adjusted Cox models (age, eGFR, LVEF and haemodynamics), UA predicts the combined endpoint and all-cause mortality in long-term follow-up