Sex-related differences in patients presenting with heart failure-related cardiogenic shock.

BACKGROUND: Heart failure-related cardiogenic shock (HF-CS) accounts for a significant proportion of all CS cases. Nevertheless, there is a lack of evidence on sex-related differences in HF-CS, especially regarding use of treatment and mortality risk in women vs. men. This study aimed to investigate potential differences in clinical presentation, use of treatments, and mortality between women and men with HF-CS. METHODS: In this international observational study, patients with HF-CS (without acute myocardial infarction) from 16 tertiary-care centers in five countries were enrolled between 2010 and 2021. Logistic and Cox regression models were used to assess differences in clinical presentation, use of treatments, and 30-day mortality in women vs. men with HF-CS. RESULTS: N = 1030 patients with HF-CS were analyzed, of whom 290 (28.2%) were women. Compared to men, women were more likely to be older, less likely to have a known history of heart failure or cardiovascular risk factors, and lower rates of highly depressed left ventricular ejection fraction and renal dysfunction. Nevertheless, CS severity as well as use of treatments were comparable, and female sex was not independently associated with 30-day mortality (53.0% vs. 50.8%; adjusted HR 0.94, 95% CI 0.75-1.19). CONCLUSIONS: In this large HF-CS registry, sex disparities in risk factors and clinical presentation were observed. Despite these differences, the use of treatments was comparable, and both sexes exhibited similarly high mortality rates. Further research is necessary to evaluate if sex-tailored treatment, accounting for the differences in cardiovascular risk factors and clinical presentation, might improve outcomes in HF-CS.

Clinical presentation, shock severity and mortality in patients with de novo versus acute-on-chronic heart failure-related cardiogenic shock.

AIMS: Heart failure-related cardiogenic shock (HF-CS) accounts for a significant proportion of CS cases. Whether patients with de novo HF and those with acute-on-chronic HF in CS differ in clinical characteristics and outcome remains unclear. The aim of this study was to evaluate differences in clinical presentation and mortality between patients with de novo and acute-on-chronic HF-CS. METHODS AND RESULTS: In this international observational study, patients with HF-CS from 16 tertiary care centres in five countries were enrolled between 2010 and 2021. To investigate differences in clinical presentation and 30-day mortality, adjusted logistic/Cox regression models were fitted. Patients (n = 1030) with HF-CS were analysed, of whom 486 (47.2%) presented with de novo HF-CS and 544 (52.8%) with acute-on-chronic HF-CS. Traditional markers of CS severity (e.g. blood pressure, heart rate and lactate) as well as use of treatments were comparable between groups. However, patients with acute-on-chronic HF-CS were more likely to have a higher CS severity and also a higher mortality risk, after adjusting for relevant confounders (de novo HF 45.5%, acute-on-chronic HF 55.9%, adjusted hazard ratio 1.38, 95% confidence interval 1.10-1.72, p = 0.005). CONCLUSION: In this large HF-CS cohort, acute-on-chronic HF-CS was associated with more severe CS and higher mortality risk compared to de novo HF-CS, although traditional markers of CS severity and use of treatments were comparable. These findings highlight the vast heterogeneity of patients with HF-CS, emphasize that HF chronicity is a relevant disease modifier in CS, and indicate that future clinical trials should account for this.

Complications in patients with cardiogenic shock on veno-arterial extracorporeal membrane oxygenation therapy: distribution and relevance. Results from an international, multicentre cohort study.

AIMS: Veno-arterial extracorporeal membrane oxygenation therapy (VA-ECMO) restores circulation and tissue oxygenation in cardiogenic shock (CS) patients, but can also lead to complications. This study aimed to quantify VA-ECMO complications and analyse their association with overall survival as well as favourable neurological outcome (cerebral performance categories 1 + 2). METHODS AND RESULTS: All-comer patients with CS treated with VA-ECMO were retrospectively enrolled from 16 centres in four countries (2005-2019). Neurological, bleeding, and ischaemic adverse events (AEs) were considered. From these, typical VA-ECMO complications were identified and analysed separately as device-related complications. n = 501. Overall, 118 were women (24%), median age was 56.0 years, median lactate was 8.1 mmol/L. Acute myocardial infarction caused CS in 289 patients (58%). Thirty-days mortality was 40% (198/501 patients). At least one device-related complication occurred in 252/486 (52%) patients, neurological AEs in 108/469 (23%), bleeding in 192/480 (40%), ischaemic AEs in 123/478 (26%). The 22% of patients with the most AEs accounted for 50% of all AEs. All types of AEs were associated with a worse prognosis. Aside from neurological ones, all AEs and device-related complications were more likely to occur in women; although prediction of AEs outside of neurological AEs was generally poor. CONCLUSION: Therapy and device-related complications occur in half of all patients treated with VA-ECMO and are associated with a worse prognosis. They accumulate in some patients, especially in women. Aside from neurological events, identification of patients at risk is difficult, highlighting the need to establish additional quantitative markers of complication risk to guide VA-ECMO treatment in CS.

Association between left ventricular ejection fraction, mortality and use of mechanical circulatory support in patients with non-ischaemic cardiogenic shock.

BACKGROUND: Currently, use of mechanical circulatory support (MCS) in non-ischaemic cardiogenic shock (CS) is predominantly guided by shock-specific markers, and not by markers of cardiac function. We hypothesise that left ventricular ejection fraction (LVEF) can identify patients with a higher likelihood to benefit from MCS and thus help to optimise their expected benefit. METHODS: Patients with non-ischaemic CS and available data on LVEF from 16 tertiary-care centres in five countries were analysed. Cox regression models were fitted to evaluate the association between LVEF and mortality, as well as the interaction between LVEF, MCS use and mortality. RESULTS: N = 807 patients were analysed: mean age 63 [interquartile range (IQR) 51.5-72.0] years, 601 (74.5%) male, lactate 4.9 (IQR 2.6-8.5) mmol/l, LVEF 20 (IQR 15-30) %. Lower LVEF was more frequent amongst patients with more severe CS, and MCS was more likely used in patients with lower LVEF. There was no association between LVEF and 30-day mortality risk in the overall study cohort. However, there was a significant interaction between MCS use and LVEF, indicating a lower 30-day mortality risk with MCS use in patients with LVEF ≤ 20% (hazard ratio 0.72, 95% confidence interval 0.51-1.02 for LVEF ≤ 20% vs. hazard ratio 1.31, 95% confidence interval 0.85-2.01 for LVEF > 20%, interaction-p = 0.017). CONCLUSION: This retrospective study may indicate a lower mortality risk with MCS use only in patients with severely reduced LVEF. This may propose the inclusion of LVEF as an adjunctive parameter for MCS decision-making in non-ischaemic CS, aiming to optimise the benefit-risk ratio.

Use of mechanical circulatory support in patients with non-ischaemic cardiogenic shock.

AIMS: Despite its high incidence and mortality risk, there is no evidence-based treatment for non-ischaemic cardiogenic shock (CS). The aim of this study was to evaluate the use of mechanical circulatory support (MCS) for non-ischaemic CS treatment. METHODS AND RESULTS: In this multicentre, international, retrospective study, data from 890 patients with non-ischaemic CS, defined as CS due to severe de-novo or acute-on-chronic heart failure with no need for urgent revascularization, treated with or without active MCS, were collected. The association between active MCS use and the primary endpoint of 30-day mortality was assessed in a 1:1 propensity-matched cohort. MCS was used in 386 (43%) patients. Patients treated with MCS presented with more severe CS (37% vs. 23% deteriorating CS, 30% vs. 25% in extremis CS) and had a lower left ventricular ejection fraction at baseline (21% vs. 25%). After matching, 267 patients treated with MCS were compared with 267 patients treated without MCS. In the matched cohort, MCS use was associated with a lower 30-day mortality (hazard ratio 0.76, 95% confidence interval 0.59-0.97). This finding was consistent through all tested subgroups except when CS severity was considered, indicating risk reduction especially in patients with deteriorating CS. However, complications occurred more frequently in patients with MCS; e.g. severe bleeding (16.5% vs. 6.4%) and access-site related ischaemia (6.7% vs. 0%). CONCLUSION: In patients with non-ischaemic CS, MCS use was associated with lower 30-day mortality as compared to medical therapy only, but also with more complications. Randomized trials are needed to validate these findings.

Timing of Active Left Ventricular Unloading in Patients on Venoarterial Extracorporeal Membrane Oxygenation Therapy.

BACKGROUND: It is currently unclear if active left ventricular (LV) unloading should be used as a primary treatment strategy or as a bailout in patients with cardiogenic shock (CS) treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). OBJECTIVES: This study sought to evaluate the association between timing of active LV unloading and implantation of VA-ECMO with outcomes of patients with CS. METHODS: Data from 421 patients with CS treated with VA-ECMO and active LV unloading at 18 tertiary care centers in 4 countries were analyzed. Patients were stratified by timing of device implantation in early vs delayed active LV unloading (defined by implantation before up to 2 hours after VA-ECMO). Adjusted Cox and logistic regression models were fitted to evaluate the association between early active LV unloading and 30-day mortality as well as successful weaning from ventilation. RESULTS: Overall, 310 (73.6%) patients with CS were treated with early active LV unloading. Early active LV unloading was associated with a lower 30-day mortality risk (HR: 0.64; 95% CI: 0.46-0.88) and a higher likelihood of successful weaning from ventilation (OR: 2.17; 95% CI: 1.19-3.93) but not with more complications. Importantly, the relative mortality risk increased and the likelihood of successful weaning from ventilation decreased almost proportionally with the time interval between VA-ECMO implantation and (delayed) initiation of active LV unloading. CONCLUSIONS: This exploratory study lends support to the use of early active LV unloading in CS patients on VA-ECMO, although the findings need to be validated in a randomized controlled trial.

Heterotopic Transcatheter Tricuspid Valve Replacement in a Patient With Carcinoid Heart Disease.

Neuroendocrine tumors can lead to carcinoid heart disease with subsequent development of severe tricuspid regurgitation due to thickening and restriction of the tricuspid leaflets. We present a patient who underwent successful heterotopic transcatheter tricuspid valve replacement for torrential tricuspid regurgitation due to carcinoid heart disease. (Level of Difficulty: Intermediate.).

Association of Repetitive Dosing of Levosimendan with Reduction of NYHA Class and NT-proBNP Levels in Decompensated Heart Failure: A Retrospective Cohort Study.

BACKGROUND: There is evidence that repetitive administration of levosimendan can improve outcome in chronic heart failure patients. OBJECTIVE: The aim of this retrospective study was to investigate the effect of therapy with levosimendan (LEV) additional to standard medical care in patients with symptomatic heart failure (HFrEF = heart failure with reduced ejection fraction) on NYHA class, NT-proBNP values, ejection fraction (EF) and body weight. PATIENTS AND METHODS: 178 participating patients (125 male, 53 female; mean age of 73 ± 13 years) were grouped according to whether LEV was given once (group 1) or repetitively (group 2). In group 2 data were analysed for first treatment with LEV (group 2a) and for the following repetitive LEV treatments (group 2b). The differentiation was required to see if there were different results for the particular groups. RESULTS: Repetitive dosing was given between two and 11 times, leading to 47 repetitive applications of LEV and a total of 225 (178 once + 47 repetitive) applications. The mean time between the repetitive dosing was 133 days or 4.3 months. LEV in addition to standard medical treatment was associated with reduction of NT-proBNP levels from 9138 to 7051 pg/mL (p < 0.05). The corresponding values in group 2a and group 2b were 8790-4717 pg/mL (p < 0.05) as well as 13,681-7581 pg/mL (p < 0.05). The ejection fraction measured by echocardiography improved from 30 to 38% in group 1, from 31 to 45% in group 2a and from 30 to 35% in group 2b (p < 0.05). Addition of LEV was associated with significant reduction of NYHA class and bodyweight in all groups. No adverse side effects (e.g., rhythm disorder, hypotension, electrolyte disorder) were seen. CONCLUSION: LEV may be useful as an additive to standard care of treatment for patients with acute de novo decompensation due to acute heart failure as well as to prevent further deterioration in patients with chronic heart failure disease at high risk for hospitalisation. Intraindividual changes in NT-proBNP levels may be useful in decision-making about the need for additional treatment options in patients with worsening heart failure.

Pathophysiology of heart failure.

Heart failure is an epidemic disease which affects about 1% to 2% of the population worldwide. Both, the etiology and phenotype of heart failure differ largely. Following a cardiac injury (e.g., myocardial infarction, increased preload or afterload) cellular, structural and neurohumoral modulations occur that affect the phenotype being present. These processes influence the cell function among intra- as well as intercellular behavior. In consequence, activation of the sympathoadrenergic and renin-angiotensin-aldosterone-system takes place leading to adaptive mechanisms, which are accompanied by volume overload, tachycardia, dyspnoea and further deterioration of the cellular function (vicious circle). There exists no heart failure specific clinical sign; the clinical symptomatic shows progressive deterioration acutely or chronically. As a measure of cellular dysfunction, the level of neurohormones (norepinephrine) and natriuretic peptides (e.g., NT-pro BNP) increase. For the diagnosis of heart failure, noninvasive (echocardiography, NMR, NT-proBNP) and invasive (heart catheterization, biopsy) diagnostic procedures are implemented. Modulation of the activated systems by ß-blocker, ACE-inhibitors and ARNI improve outcome and symptoms in heart failure patients with left ventricular dysfunction. Interventional and surgical therapy options may be performed as well. The understanding of the underlying pathophysiology of heart failure is essential to initiate the adequate therapeutic option individually for each patient. Furthermore, prevention of cardiovascular risk factors is essential to lower the risk of heart failure.