Mads J. Andersen

Lung congestion in chronic heart failure: haemodynamic, clinical, and prognostic implications

The goal of the study was to examine the prognostic impact, haemodynamic and clinical features associated with lung congestion in patients with chronic heart failure (HF).

Heart Failure with Preserved Ejection Fraction: Current Understandings and Challenges

Heart failure (HF) is the leading cause of hospitalization among older adults and the prevalence is growing with the aging populations in western countries. Approximately one-half of patients with HF have preserved ejection fraction (HFpEF). In contrast to HF with reduced EF (HFrEF), there is no proven effective treatment for HFpEF. The pathophysiology of HFpEF is complex, and the dominant mechanisms leading to symptoms of HF often vary between afflicted patients, confounding efforts to apply “one-size fits all” types of therapeutic approaches. Current treatment strategies focus on control of volume status and comorbidities, but future research aimed at individualized therapies holds promise to improve outcomes in this increasingly prevalent form of cardiac failure.

Arterial Stiffening With Exercise in Patients With Heart Failure and Preserved Ejection Fraction

BACKGROUNDnAortic stiffening and reduced nitric oxide (NO) availability may contribute to the pathophysiology ofxa0heart failure with preserved ejection fraction (HFpEF).nnnOBJECTIVESnThis study compared indices of arterial stiffness at rest and during exercise in subjects with HFpEF and hypertensive control subjects to examine their relationships to cardiac hemodynamics and determine whether exertional arterial stiffening can be mitigated by inorganic nitrite.nnnMETHODSnA total of 22 hypertensive control subjects and 98 HFpEF subjects underwent hemodynamic exercise testing with simultaneous expired gas analysis to measure oxygen consumption. Invasively measured radial artery pressure waveforms were converted to central aorticxa0waveforms by transfer function to assess integrated measures of pulsatile aortic load, including arterial compliance, resistance, elastance, and wave reflection.nnnRESULTSnArterial load and wave reflections in HFpEF were similar to those in control subjects at rest. During submaximal exercise, HFpEF subjects displayed reduced total arterial compliance and higher effective arterial elastance despite similar mean arterial pressures in control subjects. This was directly correlated with higher ventricular filling pressures and depressed cardiac output reserve (both pxa0< 0.0001). With peak exercise, increased wave reflections, impaired compliance, and increased resistance and elastance were observed in subjects with HFpEF. A subset of HFpEF subjects (nxa0=xa052) received sodium nitrite or placebo therapy in a 1:1 double-blind, randomized fashion. Compared to placebo, nitrite decreased aortic wave reflections at rest and improved arterial compliance and elastance and central hemodynamics during exercise.nnnCONCLUSIONSnAbnormal pulsatile aortic loading during exercise occurs in HFpEF independent of hypertension and is correlated with classical hemodynamic derangements that develop with stress. Inorganic nitrite mitigates arterial stiffening with exercise and improves hemodynamics, indicating that arterial stiffening with exercise is at least partially reversible. Further study is required to test effects of agents that target the NO pathway in reducing arterial stiffness in HFpEF. (Study of Exercise and Heart Function in Patients With Heart Failure and Pulmonary Vascular Disease [EXEC]; NCT01418248. Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preservedxa0Ejection Fraction; NCT01932606. Inhaled Sodium Nitrite on Heart Failure With Preserved Ejection Fraction; NCT02262078).

Invasive Hemodynamic Characterization of Heart Failure with Preserved Ejection Fraction

Recent hemodynamic studies have advanced our understanding of heart failure with preserved ejection fraction (HFpEF). Despite improved pathophysiologic insight, clinical trials have failed to identify an effective treatment for HFpEF. Invasive hemodynamic assessment can diagnose or exclude HFpEF, making it invaluable in understanding the basis of the disease. This article reviews the hemodynamic mechanisms underlying HFpEF and how they manifest clinically, discusses invasive hemodynamic assessment as a diagnostic tool, and explores how invasive hemodynamic profiling may allow understanding of pathophysiological differences and inform the design and entry criteria for future trials.

Relationships Between Biomarkers and Left Ventricular Filling Pressures at Rest and During Exercise in Patients After Myocardial Infarction

BACKGROUNDnIncreased pulmonary capillary wedge pressure (PCWP) is an independent prognostic predictor after myocardial infarction (MI), but PCWP is difficult to assess noninvasively in subjects with preserved ejection fraction (EF). We hypothesized that biomarkers would provide information regarding PCWP at rest and during exercise in subjects with preserved EF after MI.nnnMETHODS AND RESULTSnSeventy-four subjects with EF >45% and recent MI underwent right heart catheterization at rest and during a symptom-limited semisupine cycle exercise test with simultaneous echocardiography. Plasma samples were collected at rest for assessment of midregional pro-A-type natriuretic peptide (MR-proANP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3 (Gal-3), copeptin, and midregional pro-adrenomedullin (MR-proADM). Plasma levels of MR-proANP and PCWP were associated at rest (rxa0=xa00.33; Pxa0=xa0.002) and peak exercise (rxa0=xa00.35; Pxa0=xa0.002) as well as with changes in PCWP (rxa0=xa00.26; Pxa0=xa0.03). Plasma levels of NT-proBNP and PCWP were weakly associated at rest (rxa0=xa00.23; Pxa0=xa0.03) and peak exercise (rxa0=xa00.28; Pxa0=xa0.02) but not with changes in PCWP (rxa0=xa00.20; Pxa0=xa0.09). In a multivariable analysis, plasma levels of MR-proANP remained associated with rest and exercise PCWP (Pxa0<xa0.01), whereas NT-proBNP did not. Plasma levels of Gal-3, copeptin, and MR-proADM were not associated with PCWP at rest or peak exercise.nnnCONCLUSIONSnIn subjects recovering from an acute MI with preserved EF, plasma levels of natriuretic peptides, particularly MR-proANP, are associated with filling pressures at rest and during exercise.

The reservoir-wave approach to characterize pulmonary vascular-right ventricular interactions in humans

Using the reservoir-wave approach (RWA) we previously characterized pulmonary vasculature mechanics in a normal canine model. We found reflected backward-traveling waves that decrease pressure and increase flow in the proximal pulmonary artery (PA). These waves decrease right ventricular (RV) afterload and facilitate RV ejection. With pathological alterations to the pulmonary vasculature, these waves may change and impact RV performance. Our objective in this study was to characterize PA wave reflection and the alterations in RV performance in cardiac patients, using the RWA. PA pressure, Doppler-flow velocity, and pulmonary arterial wedge pressure were measured in 11 patients with exertional dyspnea. The RWA was employed to analyze PA pressure and flow; wave intensity analysis characterized PA waves. Wave-related pressure was partitioned into two components: pressures due to forward-traveling and to backward-traveling waves. RV performance was assessed by examining the work done in raising reservoir pressure and that associated with the wave components of systolic PA pressure. Wave-related work, the mostly nonrecoverable energy expended by the RV to eject blood, tended to vary directly with mean PA pressure. Where PA pressures were lower, there were pressure-decreasing/flow-increasing backward waves that aided RV ejection. Where PA pressures were higher, there were pressure-increasing/flow-decreasing backward waves that impeded RV ejection. Pressure-increasing/flow-decreasing backward waves were responsible for systolic notches in the Doppler flow velocity profiles in patients with the highest PA pressure. Pulmonary hypertension is characterized by reflected waves that impede RV ejection and an increase in wave-related work. The RWA may facilitate the development of therapeutic strategies.

Response to Letter Regarding “Differential Hemodynamic Effects of Exercise and Volume Expansion in People With and Without Heart Failure”

We thank Dr Guazzi for his interest in our study comparing the hemodynamic effects of volume loading and exercise in patients with and without heart failure with preserved ejection fraction (HFpEF).1 We agree that impairments in right ventricular (RV)–pulmonary arterial coupling are important in the pathophysiology of this disorder and that one might expect a better …