Impact of the 2022 pulmonary hypertension definition on haemodynamic classification and mortality in patients with aortic stenosis undergoing valve replacement.

Aims: With the 2022 pulmonary hypertension (PH) definition, the mean pulmonary artery pressure (mPAP) threshold for any PH was lowered from ≥25 to >20 mmHg, and the pulmonary vascular resistance (PVR) value to differentiate between isolated post-capillary PH (IpcPH) and combined pre- and post-capillary PH (CpcPH) was reduced from >3 Wood units (WU) to >2 WU. We assessed the impact of this change in the PH definition in aortic stenosis (AS) patients undergoing aortic valve replacement (AVR). Methods and results: Severe AS patients (n = 503) undergoing pre-AVR cardiac heart catheterization were classified according to both the 2015 and 2022 definitions. The post-AVR mortality [median follow-up 1348 (interquartile range 948-1885) days] was assessed. According to the 2015 definition, 219 (44% of the entire population) patients had PH: 63 (29%) CpcPH, 125 (57%) IpcPH, and 31 (14%) pre-capillary PH. According to the 2022 definition, 321 (+47%) patients were diagnosed with PH, and 156 patients (31%) were re-classified: 26 patients from no PH to IpcPH, 38 from no PH to pre-capillary PH, 38 from no PH to unclassified PH, 4 from pre-capillary PH to unclassified PH, and 50 from IpcPH to CpcPH (CpcPH: +79%). With both definitions, only the CpcPH patients displayed increased mortality (hazard ratios ≈ 4). Among the PH-defining haemodynamic components, PVR was the strongest predictor of death. Conclusion: In severe AS, the application of the 2022 PH definition results in a substantially higher number of patients with any PH as well as CpcPH. With either definition, CpcPH patients have a significantly increased post-AVR mortality.

[Heart failure with preserved left ventricular ejection fraction (HFpEF)].

INTRODUCTION: Heart failure with preserved left ventricular ejection fraction (HFpEF) is a common and very important disease entity because of its association with frequent repeat hospitalization and high mortality. Hallmarks of the underlying pathophysiology include a small left ventricular cavity due to concentric remodeling, impaired left ventricular compliance and left atrial dysfunction. This leads to an increase in left atrial and pulmonary pressure on exertion and in advanced stages of the disease already at rest with consecutive exertional dyspnea and exercise intolerance. Additional cardiovascular mechanisms including atrial fibrillation, chronotropic incompetence and coronary artery disease as well as non-cardiac co-morbidities contribute to a variable extent to the clinical picture. The diagnostic work-up is demanding and complex but the concepts have significantly improved during the last years. The study results of the Sodium Glucose cotransporter-2 inhibitors (SGLT-2-inhibitors) have revolutionized the treatment of HFpEF. In the present article, we provide an overview about the current understanding of the pathophysiology of HFpEF, the principles of the diagnostic pathways and a summary of the intervention studies in the field, and we propose an approach for the treatment in clinical practice.

Quantifying Hemodynamic Cardiac Stress and Cardiomyocyte Injury in Normotensive and Hypertensive Acute Heart Failure.

BACKGROUND: The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments. METHODS: The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90-140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324). RESULTS: In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF [1105 (611-1956) versus 827 (448-1419) pg/mL, and 5890 (2959-12,162) versus 4068 (1986-8118) pg/mL, both p < 0.001, respectively]. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF [41 (24-71) versus 33 (19-59) ng/L, p < 0.001]. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31-2.10; p < 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort. CONCLUSION: Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.

Screening for heart failure in patients with diabetes mellitus in tertiary care - A SwissDiab study.

AIMS: To evaluate the prevalence of heart failure (HF) in patients with diabetes in tertiary care, and the implementation of sodium-glucose co-transporter 2 inhibitor (SGLT2i). METHODS: Between 28.09.2020 and 31.03.2022, patients enrolled in the Swiss Diabetes Registry at one study centre were screened for HF based on the recommendations by the European Society of Cardiology. Indicated patients were referred for echocardiography and a clinical evaluation of HF, further stratified by preserved (HFpEF), mildly reduced (HFmrEF), and reduced (HFrEF) left ventricular ejection fraction. RESULTS: In total, 534 patients were screened (31.5%, type 1 diabetes (T1D); 59.7%, type 2 diabetes (T2D); 8.8%, other forms). Overall, HF was present in 11.2% (HFpEF, 56.7%; HFmrEF, 11.7%; HFrEF, 31.7%). Prevalence by diabetes type was 2.4%, T1D; 16.0%, T2D; and 10.6%, other forms. Of the identified cases, 40.0% were previously diagnosed and 60.0% were diagnosed as a result of the screening. Of the 24 patients with previously known HF, 50.0% were prescribed SGLT2i (including 2 out of 3 patients with HFrEF). CONCLUSIONS: The fact that most cases of HF were previously undiagnosed and treatment with SGLT2i could be improved highlights the need to increase awareness of HF among healthcare professionals treating patients with diabetes.

Pleural effusion in severe aortic stenosis: marker of an adverse haemodynamic constellation and poor prognosis.

AIM: Pleural effusion (PE) is a common chest radiography (CXR) finding in patients with advanced cardiac disease. The pathophysiology and clinical value of PE in this setting are incompletely defined. We aimed to assess the haemodynamic correlates and prognostic impact of PE in patients with severe aortic stenosis (AS). METHODS AND RESULTS: We studied 471 patients (mean age 74 ± 10 years) with severe AS (indexed aortic valve area 0.42 ± 0.12 cm2/m2, left ventricular ejection fraction 58 ± 12%) undergoing right heart catheterization and upright CXR prior to aortic valve replacement (AVR). Two radiologist independently evaluated all CXR for the presence of bilateral PE, unilateral, or no PE, blinded to any other data. There were 49 (10%) patients with bilateral PE, 32 (7%) patients with unilateral PE, and 390 (83%) patients with no PE. Patients with bilateral PE had the highest mean right atrial pressure, mean pulmonary artery wedge pressure (mPAWP), and pulmonary vascular resistance, and had the lowest stroke volume index while those with unilateral PE had intermediate values. In the multivariate analysis, mPAWP was an independent predictor of any PE and bilateral PE. After a median (interquartile range) post-AVR follow-up of 1361 (957-1878) days mortality was highest in patients with bilateral PE (2.7 times higher than in patients without PE), whereas patients with unilateral PE had similar mortality as those without PE. CONCLUSIONS: In severe AS patients, the presence of PE, particularly bilateral PE, is a marker of a poor haemodynamic constellation. Bilateral PE is associated with a substantially increased post-AVR mortality.

ECG left ventricular hypertrophy in aortic stenosis: Relationship with cardiac structure, invasive hemodynamics, and long-term mortality.

BACKGROUND: In aortic stenosis (AS), left ventricular hypertrophy (LVH) is the response to pressure overload and represents the substrate for a maladaptive cascade, the so-called AS-related cardiac damage. We hypothesized that in AS patients electrocardiogram (ECG) LVH not only predicts echocardiography LVH but also other noninvasive and invasive markers of cardiac damage and prognosis after aortic valve replacement (AVR). METHODS: In 279 patients with severe AS undergoing ECG, echocardiography, and cardiac catheterization before AVR, the Sokolow-Lyon index, the Cornell product, the Romhilt-Estes score, and the Peguero-Lo Presti score were assessed. RESULTS: The mean left ventricular mass index was 109 ± 34 g/m2 , and 131 (47%) patients had echocardiography LVH. The areas under the receiver operator characteristics curve (AUC) for the Sokolow-Lyon index, the Cornell product, the Romhilt-Estes score, and the Peguero-Lo Presti score for the prediction of echocardiography LVH were 0.59, 0.70, 0.63, and 0.65. The Peguero-Lo Presti score had the numerically greatest AUC for the prediction of left ventricular end-diastolic pressure >15 mmHg, mean pulmonary artery wedge pressure >15 mmHg, pulmonary vascular resistance >3 Wood units, mean right atrial pressure >14 mmHg, and stroke volume index <31 mL/m2 . After a median follow-up of 1365 (interquartile range: 931-1851) days after AVR only the Peguero-Lo Presti score was significantly associated with all-cause mortality [hazard ratio: 1.24 (95% confidence interval: 1.01-1.54); per 1 mV increase; p = .045]. CONCLUSIONS: Among severe AS patients, the Peguero-Lo Presti score is associated with abnormalities in cardiac structure including LVH, invasive measures of cardiac damage, and long-term mortality after AVR.

Pulmonary and Systemic Hemodynamics in Patients with Hyperthyroidism.

BACKGROUND: There is an association between hyperthyroidism and pulmonary hypertension. However, the prevalence of pulmonary hypertension in hyperthyroidism and the underlying mechanisms are incompletely defined. METHODS: Consecutive patients with severe hyperthyroidism, mostly due to Graves disease, were included in this single-center study. Echocardiographic assessment of pulmonary hemodynamics was performed at the time of hyperthyroidism diagnosis (baseline) and after normalization of thyroid hormones (follow-up; median 11 months). In a subset of patients, right heart catheterization and noninvasive assessment of central hemodynamics was performed. RESULTS: Among all 99 patients, 31% had pulmonary hypertension at baseline. The estimated systolic pulmonary artery pressure correlated significantly with the estimated left ventricular filling pressure (E/e'). The invasively measured systolic pulmonary artery pressure correlated well with the estimated systolic pulmonary artery pressure. Cardiac output, E/e', left and right ventricular dimensions were significantly reduced from baseline to follow-up, whereas the estimated pulmonary vascular resistance did not differ. Diastolic blood pressure was significantly higher at follow-up, with no change in systolic blood pressure. The central systolic blood pressure, however, exhibited a trend for a reduction at follow-up, while the pulse wave velocity was significantly lower at follow-up. CONCLUSIONS: Approximately one-third of patients with hyperthyroidism have evidence of pulmonary hypertension. Our data suggest that an increased cardiac output and left ventricular filling pressure are the main mechanisms underlying the elevated systolic pulmonary artery pressure in hyperthyroidism, whereas there is no evidence of significant pulmonary vascular disease.

Comprehensive vasodilatation in women with acute heart failure: Novel insights from the GALACTIC randomized controlled trial.

AIMS: Sex-specific differences in acute heart failure (AHF) are both relevant and underappreciated. Therefore, it is crucial to evaluate the risk/benefit ratio and the implementation of novel AHF therapies in women and men separately. METHODS AND RESULTS: We performed a pre-defined sex-specific analysis in AHF patients randomized to a strategy of early intensive and sustained vasodilatation versus usual care in an international, multicentre, open-label, blinded endpoint trial. Inclusion criteria were AHF with increased plasma concentrations of natriuretic peptides, systolic blood pressure ≥100 mmHg, and plan for treatment in a general ward. Among 781 eligible patients, 288 (37%) were women. Women were older (median 83 vs. 76 years), had a lower body weight (median 64.5 vs. 77.6 kg) and lower estimated glomerular filtration rate (median 48 vs. 54 ml/min/1.73 m2 ). The primary endpoint, a composite of all-cause mortality or rehospitalization for AHF at 180 days, showed a significant interaction of treatment strategy and sex (p for interaction = 0.03; hazard ratio adjusted for female sex 1.62, 95% confidence interval 1.05-2.50; p = 0.03). The combined endpoint occurred in 53 women (38%) in the intervention group and in 35 (24%) in the usual care group. The implementation of rapid up-titration of renin-angiotensin-aldosterone system (RAAS) inhibitors was less successful in women versus men in the overall cohort and in patients with heart failure with reduced ejection fraction (median discharge % target dose in patients randomized to intervention: 50% in women vs. 75% in men). CONCLUSION: Rapid up-titration of RAAS inhibitors was less successfully implemented in women possibly explaining their higher rate of all-cause mortality and rehospitalization for AHF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, unique identifier NCT00512759.

Gender-specific disease trajectories prior to the onset of COPD allow individualized screening and early intervention.

BACKGROUND: Nation-wide hospitalization databases include diagnostic information at the level of an entire population over an extended period of time. Comorbidity network and early disease development can be unveiled. Chronic obstructive pulmonary disease (COPD) is an underdiagnosed condition for which it is crucial to identify early disease indicators. The identification of gender-specific conditions preceding the onset of COPD may reveal disease progression patterns allowing for early diagnosis and intervention. The objective of the study was to investigate the antecedent hospitalization history of patients newly diagnosed with COPD and to retrace a gender-specific trajectory of coded entities prior to the onset of COPD. MATERIAL AND METHODS: A population-wide hospitalization database including information about all hospitalizations in Switzerland between 2002 and 2018 was used. COPD cases were extracted from the database and comorbidities occurring prior to the onset of COPD identified. Comorbidities significantly over-represented in COPD compared with a 1:1, age- and sex-matched control population were identified and their longitudinal evolution was analyzed. RESULTS: Between 2002 and 2018, 697,714 hospitalizations with coded COPD were recorded in Switzerland. Sixty-two diagnoses were significantly over-represented before onset of COPD. These preceding comorbidities included both well-established conditions and novel links to COPD. Early pre-conditions included nicotine and alcohol abuse, obesity and cardiovascular diseases. Later comorbidities included atrial fibrillation, diseases of the genitourinary system and pneumonia. Atherosclerotic heart diseases were more prevalent in males, whereas hypothyroidism, varicose and intestinal disorders were more frequent in females. Disease trajectories were validated using an independent data set. CONCLUSIONS: Gender-specific disease trajectories highlight early indicators and pathogenetic links between COPD and antecedent diseases and could allow for early detection and intervention.

Estimated glomerular filtration rate, haemodynamics, and mortality in patients with aortic stenosis.

BACKGROUND: In aortic stenosis (AS), estimated glomerular filtration rate (eGFR) is an important prognostic marker but its haemodynamic determinants are unknown. We investigated the correlation between eGFR and invasive haemodynamics and long-term mortality in AS patients undergoing aortic valve replacement (AVR). METHODS: We studied 503 patients [median (interquartile range) age 76 (69-81) years] with AS [indexed aortic valve area .42 (.33-.49) cm2 /m2 ] undergoing cardiac catheterization prior to surgical (72%) or transcatheter (28%) AVR. Serum creatinine was measured on the day before cardiac catheterization for eGFR calculation (CKD-EPI formula). RESULTS: The median eGFR was 67 (53-82) mL/min/1.73 m2 . There were statistically significant correlations between eGFR and mean right atrial pressure (r = -.13; p = .004), mean pulmonary artery pressure (mPAP; r = -.25; p < .001), mean pulmonary artery wedge pressure (r = -.19; p < .001), pulmonary vascular resistance (r = -.21; p < .001), stroke volume index (r = .16; p < .001), extent of coronary artery disease, and mean transvalvular gradient but not indexed aortic valve area. In multivariate linear regression, higher age, lower haemoglobin, lower mean transvalvular gradient (i.e. lower flow), lower diastolic blood pressure, and higher mPAP were independent predictors of lower eGFR. After a median post-AVR follow-up of 1348 (948-1885) days mortality was more than two-fold higher in patients in the first eGFR quartile compared to those in the other three quartiles [hazard ratio 2.18 (95% confidence interval 1.21-3.94); p = .01]. CONCLUSION: In patients with AS, low eGFR is a marker of an unfavourable haemodynamic constellation as well as important co-morbidities. This may in part explain the association between low eGFR and increased post-AVR mortality.

Systemic blood pressure in severe aortic stenosis: Haemodynamic correlates and long-term prognostic impact.

AIMS: Blood pressure (BP) targets in patients with aortic stenosis (AS) are controversial. This study sought to describe the haemodynamic profile and the clinical outcome of severe AS patients with low versus high central meaarterial pressure (MAP). METHODS AND RESULTS: Patients with severe AS (n = 477) underwent right and left heart catheterization prior to aortic valve replacement (AVR). The population was divided into MAP quartiles. The mean systolic BP, diastolic BP, and MAP in the entire population were 149 ± 25, 68 ± 11, and 98 ± 14 mmHg. Patients in the lowest MAP quartile had the lowest left ventricular ejection fraction (LVEF), systemic vascular resistance, and valvulo-arterial impedance, whereas there were no significant differences in mean right atrial pressure, mean pulmonary artery wedge pressure, pulmonary vascular resistance, and stroke volume index across MAP quartiles. However, left ventricular stroke work index (LVSWI) was lowest in patients in the lowest and highest in those in the highest MAP quartile. After a median (interquartile range) post-AVR follow-up of 3.7 (2.6-5.2) years, mortality was highest in patients in the lowest MAP quartile [hazard ratio 3.08 (95% confidence interval 1.21-7.83); P = 0.02 for lowest versus highest quartile]. In the multivariate analysis, lower MAP [hazard ratio 0.78 (95% confidence interval 0.62-0.99) per 10 mmHg increase; P = 0.04], higher mean right atrial pressure and lower LVEF were independent predictors of death. CONCLUSIONS: In severe AS patients, lower MAP reflects lower systemic vascular resistance and valvulo-arterial impedance, which may help to preserve stroke volume and filling pressures despite reduced left ventricular performance, and lower MAP is a predictor of higher long-term post-AVR mortality.

Pulmonary Congestion by Conventional Chest Radiography: Relationship With Hemodynamics and Mortality in Patients With Severe Aortic Stenosis.

Background: The relationship between chest radiograph (CXR) findings of pulmonary congestion and invasive hemodynamics and clinical outcomes in patients with cardiac diseases is unclear. We assessed the correlation between a CXR-based congestion score (RxCS) and the mean pulmonary artery wedge pressure (mPAWP) and the prognostic impact of RxCS and mPAWP in severe aortic stenosis (AS). Methods: In 471 patients with severe AS undergoing right heart catheterization and upright CXR, the RxCS was calculated (6 items, maximum score: 10 points) independently by 2 radiologists (average value taken) blinded to clinical data. Congestion was defined as an RxCS > 1. Four patterns were defined based on the presence or absence of congestion (C+ or C-) and elevated (> 15 mm Hg) or normal mPAWP (P+ or P-). Results: The median (interquartile range) RxCS was 1 (0-2). Patients with an RxCS > 1 (n = 207) had a higher mean right atrial pressure, mean pulmonary artery pressure, mPAWP, and pulmonary vascular resistance than patients with an RxCS ≤ 1 (n = 264). However, the correlation between the RxCS and the mPAWP was moderate only (r = 0.45). Patients with a C+/P+ pattern had the worst hemodynamics, whereas C-/P- patients had the most favourable constellation. After a median post-valve replacement follow-up of 1361 days, mortality was higher in patients with RxCs > 1 vs ≤ 1 as well as mPAWP > 15 mm Hg vs ≤15 mm Hg. Mortality was highest in C+/P+ patients and lowest in C-/P- patients, whereas it was intermediate in C-/P+ and C+/P- patients. Conclusions: In AS patients, RxCS and mPAWP have a significant but moderate correlation. Both RxCS and mPAWP provide prognostic information.

Contexte: Des zones floues persistent quant au lien entre les signes de congestion pulmonaire à la radiographie thoracique, les examens hémodynamiques invasifs et les résultats cliniques chez les patients atteints de maladies cardiaques. Nous avons donc évalué, d'une part, la corrélation entre le score radiologique de congestion pulmonaire et la pression capillaire pulmonaire moyenne et, d'autre part, la valeur pronostique du score radiologique de congestion pulmonaire et de la pression capillaire pulmonaire moyenne dans les cas de sténose aortique sévère. Méthodologie: Chez 471 patients atteints d'une sténose aortique sévère soumis à un cathétérisme du cœur droit et à une radiographie thoracique en position debout, un score radiologique de congestion pulmonaire a été calculé (6 items, score maximal de 10 points) de façon indépendante par deux radiologistes (la valeur retenue étant la moyenne) qui ne connaissaient pas les données cliniques des patients. La congestion correspondait à un score radiologique de congestion pulmonaire > 1. Quatre types ont été définis en fonction de la présence ou de l'absence de congestion (C+ ou C­) et d'une valeur de pression capillaire pulmonaire moyenne élevée (>15 mmHg) ou normale (P+ ou P­). Résultats: La médiane (écart interquartile) du score radiologique de congestion a été de 1 (0-2). Les patients dont le score radiologique de congestion était > 1 (n = 207) présentaient des valeurs moyennes plus élevées pour la pression auriculaire droite, la pression artérielle pulmonaire, la pression capillaire pulmonaire et la résistance vasculaire pulmonaire que les patients dont le score radiologique de congestion était ≤ 1 (n = 264). Cependant, la corrélation entre le score radiologique de congestion et la pression capillaire pulmonaire moyenne n'était que modérée (r = 0,45). Les patients de type C+/P+ avaient le profil hémodynamique le plus défavorable, tandis que les patients de type C­/P­ avaient le profil le plus favorable. À l'issue d'un suivi médian de 1361 jours après un remplacement valvulaire, la mortalité était plus élevée chez les patients dont le score radiologique de congestion était > 1 vs un score ≤ 1, de même que chez les patients dont la pression capillaire pulmonaire moyenne était > 15 mmHg vs une valeur ≤ 15 mmHg. La mortalité la plus élevée a été observée chez les patients de type C+/P+, et la plus faible, chez les patients de type C­/P­, tandis qu'elle était intermédiaire chez les patients de types C­/P+ et C+/P­. Conclusions: Chez les patients atteints d'une sténose aortique, on constate une corrélation significative mais modérée entre le score radiologique de congestion pulmonaire et la pression capillaire pulmonaire moyenne. Ces paramètres revêtent tous deux une valeur pronostique.

Budget Impact of Intravenous Iron Therapy with Ferric Carboxymaltose in Patients with Chronic Heart Failure with Reduced Ejection Fraction (HFrEF) and Iron Deficiency in Switzerland.

AIMS: A budget impact analysis compared treating patients with heart failure (HF) and reduced ejection fraction (HFrEF) and iron deficiency (ID) in Switzerland with intravenous ferric carboxymaltose (FCM) or placebo. METHODS: Clinical data from four international randomized trials showed that FCM versus placebo treatment was associated with a reduced hospitalization rate due to HF. The budget impact of this was modelled over 1 year. Hospital treatment costs for HFrEF, FCM drug costs, and estimated patient numbers were based on published data, official tariffs, specially commissioned analyses of SwissDRG data, and clinical and diagnosis-related groups (DRG) coding expert opinion. The original cost year was 2015. Sensitivity analyses were conducted including updated unit costs from 2019/2020. RESULTS: FCM treatment was associated with average cost savings of Swiss Francs (SFr) 503 per patient per year from the perspective of the Swiss mandatory health insurance system. Extrapolating across all eligible HFrEF patients with ID in Switzerland, this amounted to estimated savings of SFr 23,336,873. Sensitivity analyses showed these results to be robust in the face of changes to input parameters like treatment costs, different hospital settings, updated unit costs, and including outpatient treatment and patient co-payments in the analysis. CONCLUSIONS: The present analysis shows that using FCM to treat HFrEF patients with ID in line with current guideline recommendations resulted not only in medical benefits but also in significant cost savings. The analysis also provides an example of the pitfalls of transferring economic evaluation results, even between countries with similar hospital reimbursement systems.

[Therapy of Heart Failure with Reduced Ejection Fraction: What's New in the 2021 Guidelines?] / Therapie der Herzinsuffizienz mit reduzierter Auswurffraktion: Was ist neu in den Leitlinien 2021?

Therapy of Heart Failure with Reduced Ejection Fraction: What's New in the 2021 Guidelines? Abstract. The spectrum of treatment options for patients with heart failure with reduced ejection fraction (HFrEF) has substantially expanded over the last years. The 2021 guidelines of the European Society of Cardiology propose a new treatment algorithm for patients with HFrEF and define the role of the currently available drugs, interventions and devices in this context. The new standard is a basic therapy consisting of four drugs with different mechanisms of action for all patients with HFrEF: an angiotensin-converting enzyme inhibitor, a betablocker, a mineralocorticoid antagonist, and a sodium glucose co-transporter-2 inhibitor. Additional drugs and/or interventions/devices are indicated depending on the response to the four-drug basic therapy (which has to be up-titrated to the maximally tolerated doses) and the clinical phenotype. In the present article, we discuss the available drugs and devices, their role in the proposed HFrEF treatment algorithm and clinically relevant practical aspects.

Pulmonary hypertension in aortic valve stenosis.

In patients with severe aortic stenosis (AS), pulmonary hypertension (PH) typically is indicative of a decompensated disease state with exhausted compensatory mechanisms of the left ventricle, meaning a heart failure state resulting from AS-related "cardiac injury". In the present review article, we discuss new insights into the pathophysiology of AS-induced PH, the prognostic impact, and potential options to prevent and treat PH in this setting. We emphasize recent data from studies focused on invasive hemodynamics in patients with severe AS that are being evaluated for aortic valve replacement, particularly the key relevance of combined pre- and post-capillary PH. This latter represents an advanced form of cardiac injury that is often associated with right ventricular dysfunction and poor prognosis. Given this context, we highlight the relevance of performing right heart catheterization in combination with non-invasive imaging for the comprehensive assessment of AS patients that are being evaluated for aortic valve replacement. Such comprehensive assessment plays a key role not only to precisely define the extent of AS-related cardiac injury but also to distinguish those PH forms that are unrelated to AS.