[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.

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.

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.

Valor pronóstico de las frecuencias cardiacas bajas en pacientes ingresados con infarto agudo de miocardio / Prognostic value of low heart rates in patients admitted with acute myocardial infarction

Introducción y objetivos: Las escalas de predicción de riesgo utilizadas en síndromes coronarios agudos (SCA) utilizan modelos incrementales para estimar mortalidad para frecuencias cardiacas (FCs)> 60 lpm. Sin embargo, estudios previos comunicaron una relación no lineal entre la FC y los eventos, lo que sugiere que la FC baja puede tener un papel pronóstico no reconocido. El objetivo fue valorar el impacto pronóstico de las FCs baja en el SCA, definida como frecuencia cardiaca de admisión <50 lpm. Métodos: El estudio analizó datos del registro AMIS Plus, una cohorte de pacientes hospitalizados con SCA entre 1999 y 2021. El criterio de valoración principal fue la mortalidad hospitalaria por todas las causas, mientras que el compuesto de mortalidad por todas las causas se estableció por eventos cardiacos/cerebrovasculares mayores como secundario. Se adoptó una metodología estadística multinivel para evaluar el papel pronóstico de la FC baja en el SCA. Resultados: Se incluyó a 51.001 pacientes. La estimación cruda mostró una distribución bimodal de las variables resultados primaria y secundaria a FCs bajas y altas. Se observó una relación no lineal entre FCs y mortalidad intrahospitalaria mediante análisis restringido de spline cúbico. Una FC entre 50-75 mostró menor mortalidad que FC <50 lpm (OR=0,67; IC95%, 0,47-0,99) solo tras el análisis primario multivariado, no confirmado tras análisis múltiples de sensibilidad. Tras la puntuación de propensión emparejada, se hizo evidente el desvanecimiento progresivo del papel pronóstico de la FC <50 lpm. Conclusiones: Las FCs baja al ingreso en SCA se asocian a una mayor tasa cruda de eventos adversos. No obstante, tras la corrección de las diferencias basales, no se confirmó el papel pronóstico de la FC baja, sino que representa más bien un marcador de morbilidad subyacente. Estos resultados pueden ser clínicamente relevantes para mejorar la precisión de las puntuaciones de riesgo en el SCA.(AU)

Introduction and objectives: The risk prediction scores adopted in acute coronary syndromes (ACS) use incremental models to estimate mortality for heart rate (HR) above 60 bpm. Nonetheless, previous studies reported a nonlinear relationship between HR and events, suggesting that low HR may have an unrecognized prognostic role. We aimed to assess the prognostic impact of low HR in ACS, defined as admission HR <50 bpm. Methods: This study analyzed data from the AMIS Plus registry, a cohort of hospitalized patients with ACS between 1999 and 2021. The primary endpoint was in-hospital all-cause mortality, while a composite of all-cause mortality, major cardiac/cerebrovascular events was set as the secondary endpoint. A multilevel statistical method was used to assess the prognostic role of low HR in ACS. Results: The study included 51 001 patients. Crude estimates showed a bimodal distribution of primary and secondary endpoints with peaks at low and high HR. A nonlinear relationship between HR and in-hospital mortality was observed on restricted cubic spline analysis. An HR of 50 to 75 bpm showed lower mortality than HR <50 bpm (OR, 0.67; 95%CI, 0.47-0.99) only after primary multivariable analysis, which was not confirmed after multiple sensitivity analyses. After propensity score matching, progressive fading of the prognostic role of HR <50 bpm was evident. Conclusions: Low admission HR in ACS is associated with a higher crude rate of adverse events. Nonetheless, after correction for baseline differences, the prognostic role of low HR was not confirmed. Therefore, low HR probably represents a marker of underlying morbidity. These results may be clinically relevant in improving the accuracy of risk scores in ACS.(AU)

Patients With AMI and Severely Reduced LVEF, a Well-Defined, Still Extremely Vulnerable Population (Insights from AMIS Plus Registry).

Left ventricular ejection fraction (LVEF) represents one of the strongest predictors of both in-hospital and long-term prognosis in acute myocardial infarction (AMI). Temporal trends data coming from real-world experiences focused on patients with AMI with severely reduced LVEF (i.e., <30%) are lacking. In a total of 48,543 screened patients with AMI included in the Acute Myocardial Infarction in Switzerland Plus Registry between 2005 and 2020, data on LVEF were available for 23,510 patients. Study patients were classified according to LVEF as patients with AMI with or without severely reduced LVEF (i.e., patients with LVEF <30% and ≥30%, respectively). Overall, 1,657 patients with AMI (7%) displayed severely reduced LVEF. The prevalence of severe LVEF reduction constantly decreased over the study period (from 11% to 4%, p <0.001). In the subgroup of patients with severely reduced LVEF, a significant increase in revascularization rate was observed (from 61% to 84%, p <0.001); however, in-hospital mortality did not significantly decrease and remained well above 20% over the study period (from 23% to 26%, p = 0.65). At discharge, prescription of optimal cardioprotective therapy (defined as an association of renin-angiotensin-aldosterone-system inhibitors, ß-blocker, and mineral corticoid receptor antagonist) remained low across the study period (from 17% in 2011 to 20%, p = 0.96). In conclusion, patients with AMI with severely reduced LVEF remain a fragile subgroup of patients with an in-hospital mortality that did not significantly decrease and remained well above 20% over the study period. Moreover, access at discharge to optimal cardioprotective therapy remains suboptimal. Efforts are, therefore, needed to improve prognosis and access to guidelines-directed therapies in this fragile population.

Twenty-year trends in the prevalence of modifiable cardiovascular risk factors in young acute coronary syndrome patients hospitalized in Switzerland.

AIMS: Modifiable cardiovascular risk factors (RFs) play a key role in the development of coronary artery disease. We evaluated 20-year trends in RF prevalence among young adults hospitalized with acute coronary syndromes (ACS) in Switzerland. METHODS AND RESULTS: Data were analysed from the Acute Myocardial Infarction in Switzerland (AMIS) Plus registry from 2000 to 2019. Young patients were defined as those aged <50 years. Among 58 028 ACS admissions, 7073 (14.1%) were young (median 45.6 years, IQR 42.0-48.0), of which 91.6% had at least one modifiable RF and 59.0% had at least two RFs. Smoking was the most prevalent RF (71.4%), followed by dyslipidaemia (57.3%), hypertension (35.9%), obesity (21.7%), and diabetes (10.1%). Compared with older patients, young patients were more likely to be obese (21.7% vs. 17.4%, P < 0.001) and active smokers (71.4% vs. 33.9%, P < 0.001). Among young patients, between 2000 and 2019, there was a significant increase in the prevalence of hypertension from 29.0% to 51.3% and obesity from 21.2% to 27.1% (both Ptrend < 0.001) but a significant decrease in active smoking from 72.5% to 62.5% (Ptrend = 0.02). There were no significant changes in the prevalence of diabetes (Ptrend = 0.32) or dyslipidaemia (Ptrend = 0.067). CONCLUSION: Young ACS patients in Switzerland exhibit a high prevalence of RFs and are more likely than older patients to be obese and smokers. Between 2000 and 2019, RF prevalence either increased or remained stable, except for smoking which decreased but still affected approximately two-thirds of young patients in 2019. Public health initiatives targeting RFs in young adults in Switzerland are warranted.

We evaluated the prevalence of risk factors (RFs) among young patients admitted with ACS in Switzerland between 2000 and 2019. Young ACS patients in Switzerland exhibited a high prevalence of RFs. There was a significant increase in the prevalence of hypertension and obesity. Despite a significant decrease, active smoking remained the most prevalent RF. These findings strongly suggest that public health initiatives targeting RFs in young adults in Switzerland are warranted.

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.

Prognostic value of low heart rates in patients admitted with acute myocardial infarction.

INTRODUCTION AND OBJECTIVES: The risk prediction scores adopted in acute coronary syndromes (ACS) use incremental models to estimate mortality for heart rate (HR) above 60 bpm. Nonetheless, previous studies reported a nonlinear relationship between HR and events, suggesting that low HR may have an unrecognized prognostic role. We aimed to assess the prognostic impact of low HR in ACS, defined as admission HR <50 bpm. METHODS: This study analyzed data from the AMIS Plus registry, a cohort of hospitalized patients with ACS between 1999 and 2021. The primary endpoint was in-hospital all-cause mortality, while a composite of all-cause mortality, major cardiac/cerebrovascular events was set as the secondary endpoint. A multilevel statistical method was used to assess the prognostic role of low HR in ACS. RESULTS: The study included 51 001 patients. Crude estimates showed a bimodal distribution of primary and secondary endpoints with peaks at low and high HR. A nonlinear relationship between HR and in-hospital mortality was observed on restricted cubic spline analysis. An HR of 50 to 75 bpm showed lower mortality than HR <50 bpm (OR, 0.67; 95%CI, 0.47-0.99) only after primary multivariable analysis, which was not confirmed after multiple sensitivity analyses. After propensity score matching, progressive fading of the prognostic role of HR <50 bpm was evident. CONCLUSIONS: Low admission HR in ACS is associated with a higher crude rate of adverse events. Nonetheless, after correction for baseline differences, the prognostic role of low HR was not confirmed. Therefore, low HR probably represents a marker of underlying morbidity. These results may be clinically relevant in improving the accuracy of risk scores in ACS.

Reducing gap in pre-hospital delay between women and men presenting with ST-elevation myocardial infarction.

AIMS: This study aimed to analyse changes in pre-hospital delay over time in women and men presenting with ST-elevation myocardial infarction (STEMI) in Switzerland. METHODS AND RESULTS: AMIS Plus registry data of patients admitted for STEMI between 2002 and 2019 were analysed using multivariable quantile regression including the following covariates: interaction between sex and admission year, age, diabetes, pain at presentation, myocardial infarction (MI) history, heart failure history, hypertension, and renal disease. Among the 15,350 patients included (74.5% men), the median (interquartile range) delay between 2002 and 2019 was 150 (84; 345) min for men and 180 (100; 414) min for women. The unadjusted median pre-hospital delay significantly decreased over time for both sexes but the decreasing trend was stronger for women. Specifically, the unadjusted sex differences in delay decreased from 60 min in 2002 (P = 0.0042) to 40.5 min in 2019 (P = 0.165). The multivariable model revealed a significant interaction between sex and admission year (P = 0.038) indicating that the decrease in delay was stronger for women (-3.3 min per year) than for men (-1.6 min per year) even after adjustment. The adjusted difference between men and women decreased from 26.93 min in 2002 to -1.97 min for women in 2019. CONCLUSION: Over two decades, delay between symptom onset and hospital admission in STEMI decreased significantly for men and women. The decline was more pronounced in women, leading to the sex gap disappearing in the adjusted analysis for 2019.

Because the delay between onset of heart attack symptoms and hospital admission was higher in women in the past, this study analysed whether pre-hospital delay has shortened in general since 2002 as well as in women and men separately.Our study showed that the pre-hospital delay steadily decreased for both sexes but the decrease was greater in womenAfter considering differences in patient characteristics, such as higher age and less previous heart attacks in women, by 2019 the delay was nearly the same for women and men.

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.

Sex-specific evaluation and redevelopment of the GRACE score in non-ST-segment elevation acute coronary syndromes in populations from the UK and Switzerland: a multinational analysis with external cohort validation.

BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) 2.0 score was developed and validated in predominantly male patient populations. We aimed to assess its sex-specific performance in non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and to develop an improved score (GRACE 3.0) that accounts for sex differences in disease characteristics. METHODS: We evaluated the GRACE 2.0 score in 420 781 consecutive patients with NSTE-ACS in contemporary nationwide cohorts from the UK and Switzerland. Machine learning models to predict in-hospital mortality were informed by the GRACE variables and developed in sex-disaggregated data from 386 591 patients from England, Wales, and Northern Ireland (split into a training cohort of 309 083 [80·0%] patients and a validation cohort of 77 508 [20·0%] patients). External validation of the GRACE 3.0 score was done in 20 727 patients from Switzerland. FINDINGS: Between Jan 1, 2005, and Aug 27, 2020, 400 054 patients with NSTE-ACS in the UK and 20 727 patients with NSTE-ACS in Switzerland were included in the study. Discrimination of in-hospital death by the GRACE 2.0 score was good in male patients (area under the receiver operating characteristic curve [AUC] 0·86, 95% CI 0·86-0·86) and notably lower in female patients (0·82, 95% CI 0·81-0·82; p<0·0001). The GRACE 2.0 score underestimated in-hospital mortality risk in female patients, favouring their incorrect stratification to the low-to-intermediate risk group, for which the score does not indicate early invasive treatment. Accounting for sex differences, GRACE 3.0 showed superior discrimination and good calibration with an AUC of 0·91 (95% CI 0·89-0·92) in male patients and 0·87 (95% CI 0·84-0·89) in female patients in an external cohort validation. GRACE 3·0 led to a clinically relevant reclassification of female patients to the high-risk group. INTERPRETATION: The GRACE 2.0 score has limited discriminatory performance and underestimates in-hospital mortality in female patients with NSTE-ACS. The GRACE 3.0 score performs better in men and women and reduces sex inequalities in risk stratification. FUNDING: Swiss National Science Foundation, Swiss Heart Foundation, Lindenhof Foundation, Foundation for Cardiovascular Research, and Theodor-Ida-Herzog-Egli Foundation.

Optimized Treatment of Refractory Hypercholesterolemia in Patients With Atherosclerotic Cardiovascular Disease or Heterozygous Familial Hypercholesterolemia With Alirocumab (OPTIMIZE).

Background: Low-density lipoprotein cholesterol (LDL-C) is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). In confirmatory trials, proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab substantially lowered LDL-C and reduced cardiovascular morbidity and mortality. However, the routine clinical use of alirocumab in Switzerland has not yet been studied. Methods: In this prospective nation-wide cohort study, we aimed to investigate the patient profile and routine clinical efficacy and safety of alirocumab in 207 patients with ASCVD or heterozygous familial hypercholesterolemia and increased LDL-C despite maximally tolerated statin therapy. LDL-C was measured at baseline and after 3-months follow-up. Results: Overall, mean age was 63 ± 11 years, 138 (67%) were men, and 168 (81%) had statin intolerance (SI). Patients with SI had a higher baseline LDL-C (4.3 ± 1.4 vs. 3.3 ± 1.4 mmol/l; p < 0.001) and less frequently ASCVD (71% vs. 95%; p = 0.002). After 3 months of treatment with alirocumab, LDL-C was reduced from 4.1 ± 1.5 to 2.0 ± 1.2 mmol/l (50.5%; p < 0.001). Mean absolute and relative reductions in LDL-C were similar in patients with vs. without SI (2.2 ± 1.2 vs. 1.9 ± 1.3 mmol/l; p = 0.24 and 49.0 vs. 56.6%; p = 0.11, respectively). In total, adverse events were recorded in 25 (12%) patients, with no new safety signals. Conclusions: In routine clinical practice, alirocumab was predominantly used in patients with SI suggesting that the great majority of patients with insufficient LDL-C control who would be candidates for alirocumab are not receiving this therapeutic option in Switzerland. LDL-C lowering was potent and similar in patients with and without SI, replicating the favorable efficacy-safety profile of alirocumab from randomized trials.

[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.

Effectiveness, Adherence, and Safety of Evolocumab in a Swiss Multicenter Prospective Observational Study.

INTRODUCTION: The aims of this study were to describe patient characteristics, lipid parameters, lipid-lowering drug use, and safety of patients receiving evolocumab in a real-world clinical setting. METHODS: We conducted a 1-year multicenter observational study of adults using evolocumab with confirmed atherosclerotic cardiovascular disease (CVD) or at high cardiovascular risk, and elevated LDL-C despite maximally tolerated statin doses. An e-health application optionally supported patient management. The primary outcome was change in lipid parameters over time. The secondary outcomes included evolocumab safety. RESULTS: Of 100 participants, 81% had pre-existing CVD, 71% self-reported statin-related muscle symptoms, 44% received statins. All patients received evolocumab, 65% were PCSK9i pre-treated at baseline. PCSK9i-naïve patients achieved a mean LDL-C reduction of 60% within 3 months of evolocumab treatment, which was maintained thereafter; 74% achieved LDL-C < 1.8 mmol/L at least once during observation, 69% attained < 1.4 mmol/L. In PCSK9i pre-treated patients, LDL-C remained stable throughout; 79% and 74% attained < 1.8 mmol/L and < 1.4 mmol/L, respectively, at least once. Goal attainment was higher with any combination of evolocumab, statin, and/or ezetimibe. Overall, 89% self-reported full evolocumab adherence. Treatment-emergent adverse events (TEAE) were reported in 30% of patients, two serious TEAEs occurred in one patient; three patients discontinued evolocumab because of TEAEs. CONCLUSION: In real-world clinical practice, evolocumab was mainly used in patients with statin intolerance and pre-existing CVD. In this population, adherence to evolocumab and low LDL-C levels were maintained over 1 year, with better LDL-C goal achievement in patients using evolocumab in combination with other lipid-lowering drugs. Safety of evolocumab was similar to that documented in randomized controlled trials.