Congestion in heart failure: a contemporary look at physiology, diagnosis and treatment

Boorsma, Eva M; Maaten, Jozine M. ter; Damman, Kevin; Dinh, Wilfried; Gustafsson, Finn; Goldsmith, Steven R.; Burkhoff, Daniel; Zannad, Faı̈ez; Udelson, James E.; Voors, Adriaan A.

doi:10.1038/s41569-020-0379-7

Cited by 154 publications

(149 citation statements)

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“…In our data no effect on serum sodium could be found, which might be explained by the fact that only a small proportion of patients presented with hyponatraemia and the lowest measured sodium upon admission was 129 mmol/L. Moreover, this might position SGLT2 inhibitors as a treatment for tissue congestion or residual congestion as increased plasma osmolality attracts fluid from the interstitial space into the blood stream 24 . This notion is supported by earlier findings that the SGLT2 inhibitor dapagliflozin has been calculated to reduce interstitial fluid volume three times more than it reduces blood volume, compared to an interstitial fluid reduction of only 66% of the reduction in blood volume by bumetanide 25 .…”

Section: Discussioncontrasting

confidence: 67%

Effects of empagliflozin on renal sodium and glucose handling in patients with acute heart failure

Boorsma

Beusekamp

Maaten

et al. 2020

European J of Heart Fail

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Aims Sodium–glucose co‐transporter 2 (SGLT2) inhibitors improve clinical outcome in patients with heart failure (HF), but the mechanisms behind their beneficial effects are not yet fully understood. We examined the effects of empagliflozin on renal sodium and glucose handling in patients with acute HF. Methods and results This study was a pre‐defined sub‐study of a double‐blind, randomized, placebo‐controlled, multicentre study (EMPA‐RESPONSE‐AHF). Patients were allocated within 24 h of an acute HF admission to either empagliflozin 10 mg/day (n = 40) or placebo (n = 39) for 30 days. Markers of glucose and sodium handling were measured daily during the first 96 h and at day 30. Patients were 76 (range 38–89) years old and 33% had diabetes. The use of loop diuretics during the first 96 h was similar in both groups. Empagliflozin increased fractional glucose excretion with a peak after 24 h (21.8% vs. 0.1%; P < 0.001), without affecting plasma glucose concentration, while fractional sodium and chloride excretion and urinary osmolality remained unchanged (P >0.3 for all). However, empagliflozin increased plasma osmolality (delta osmolality at 72 h: 5 ± 8 vs. 2 ± 5 mOsm/kg; P = 0.049). Finally, there was an early decline in estimated glomerular filtration rate with empagliflozin vs. placebo (−10 ± 12 vs. −2 ± 12 mL/min/1.73 m2; P = 0.009), which recovered within 30 days. Conclusion In patients with acute HF, empagliflozin increased fractional glucose excretion and plasma osmolality, without affecting fractional sodium excretion or urine osmolality and caused a temporary decline in estimated glomerular filtration rate. This suggests that empagliflozin stimulates osmotic diuresis through increased glycosuria rather than natriuresis in patients with acute HF.

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Section: Discussioncontrasting

confidence: 67%

Effects of empagliflozin on renal sodium and glucose handling in patients with acute heart failure

Boorsma

Beusekamp

Maaten

et al. 2020

European J of Heart Fail

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“…Despite these echocardiographic parameters, poor prognostic Q3 group showed frequent usage of intubation, non-invasive positive pressure ventilator, carperitide, and calcium channel blocker injection for initial treatment, frequent prior usage of loop diuretics, and higher NT-proBNP elevation on admission. The frequent usage of loop diuretics might directly affect the increase of plasma osmolality on admission [ 26 ]. These aspects ensured that Q3 group was in more decompensated hemodynamic status on admission paradoxically from the echocardiographic observations, and it seemed reasonable that those patients served poor outcomes.…”

Section: Discussionmentioning

confidence: 99%

Prognostic relevance of elevated plasma osmolality on admission in acute decompensated heart failure with preserved ejection fraction: insights from PURSUIT-HFpEF registry

Nakagawa¹,

Yasumura²,

Yoshida³

et al. 2021

BMC Cardiovasc Disord

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Background Complicated pathophysiology makes it difficult to identify the prognosis of heart failure with preserved ejection fraction (HFpEF). While plasma osmolality has been reported to have prognostic importance, mainly in heart failure with reduced ejection fraction (HFrEF), its prognostic meaning for HFpEF has not been elucidated. Methods We prospectively studied 960 patients in PURSUIT-HFpEF, a multicenter observational study of acute decompensated HFpEF inpatients. We divided patients into three groups according to the quantile values of plasma osmolality on admission. During a follow-up averaging 366 days, we examined the primary composite endpoint of cardiac mortality or heart failure re-admission using Kaplan–Meier curve analysis and Cox proportional hazard testing. Results 216 (22.5%) patients reached the primary endpoint. Kaplan–Meier curve analysis revealed that the highest quantile of plasma osmolality on admission (higher than 300.3 mOsm/kg) was significantly associated with adverse outcomes (Log-rank P = 0.0095). Univariable analysis in the Cox proportional hazard model also revealed significantly higher rates of adverse outcomes in the higher plasma osmolality on admission (hazard ratio [HR] 7.29; 95% confidence interval [CI] 2.25–23.92, P = 0.0009). Multivariable analysis in the Cox proportional hazard model also showed that higher plasma osmolality on admission was significantly associated with adverse outcomes (HR 5.47; 95% CI 1.46–21.56, P = 0.0113) independently from other confounding factors such as age, gender, comorbid of atrial fibrillation, hypertension history, diabetes, anemia, malnutrition, E/e′, and N-terminal pro-B-type natriuretic peptide elevation. Conclusions Higher plasma osmolality on admission was prognostically important for acute decompensated HFpEF inpatients.

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“…The splanchnic veins contain anywhere between 20% and 50% of the total blood volume 58 . As a result of sympathetic nerve overactivity in HF, vasoconstriction in this compartment forces movement of venous blood to the circulating compartment, which contributes to HF decompensation; this may be particularly important in acute HF 58–60 . As an additional component, high IAP compresses intra‐abdominal and intrathoracic blood vessels, compromising microvascular blood flow 61 .…”

Section: Clinical Scenarios Associated With Congestive Nephropathymentioning

confidence: 99%

“…particularly important in acute HF. [58][59][60] As an additional component, high IAP compresses intra-abdominal and intrathoracic blood vessels, compromising microvascular blood flow. 61 Diminished venous drainage results in renal, intestinal, and mesenteric venous congestion, oedema, and ischaemia.…”

Section: Chronic Kidney Disease and Pulmonary Hypertensionmentioning

confidence: 99%

Congestive nephropathy: a neglected entity? Proposal for diagnostic criteria and future perspectives

et al. 2020

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Venous congestion has emerged as an important cause of renal dysfunction in patients with cardiorenal syndrome. However, only limited progress has been made in differentiating this haemodynamic phenotype of renal dysfunction, because of a significant overlap with pre‐existing renal impairment due to long‐term hypertension, diabetes, and renovascular disease. We propose congestive nephropathy (CN) as this neglected clinical entity. CN is a potentially reversible subtype of renal dysfunction associated with declining renal venous outflow and progressively increasing renal interstitial pressure. Venous congestion may lead to a vicious cycle of hormonal activation, increased intra‐abdominal pressure, excessive renal tubular sodium reabsorption, and volume overload, leading to further right ventricular (RV) stress. Ultimately, renal replacement therapy may be required to relieve diuretic‐resistant congestion. Effective decongestion could preserve or improve renal function. Congestive acute kidney injury may not be associated with cellular damage, and complete renal function restoration may be a confirmatory diagnostic criterion. In contrast, a persistently low renal perfusion pressure might induce renal dysfunction and histopathological lesions with time. Thus, urinary markers may differ. CN is mostly seen in biventricular heart failure but may also occur secondary to pulmonary arterial hypertension and elevated intra‐abdominal pressure. An increase in central venous pressure to >6 mmHg is associated with a steep decrease in glomerular filtration rate. However, the central venous pressure range that can provide an optimal balance of RV and renal function remains to be determined. We propose criteria to identify cardiorenal syndrome subgroups likely to benefit from decongestive or pulmonary hypertension‐specific therapies and suggest areas for future research.

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Congestion in heart failure: a contemporary look at physiology, diagnosis and treatment

Abstract: 9universite de lorraine, Inserm, centre d'Investigations cliniques-Plurithematique 14-33, and Inserm u1116, cHru, F-crIN INI-crct (cardiovascular and renal clinical trialists),

Cited by 154 publications

References 138 publications

Effects of empagliflozin on renal sodium and glucose handling in patients with acute heart failure

Effects of empagliflozin on renal sodium and glucose handling in patients with acute heart failure

Prognostic relevance of elevated plasma osmolality on admission in acute decompensated heart failure with preserved ejection fraction: insights from PURSUIT-HFpEF registry

Congestive nephropathy: a neglected entity? Proposal for diagnostic criteria and future perspectives

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