[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.

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.

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.

[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.

Hemodynamics Prior to Valve Replacement for Severe Aortic Stenosis and Pulmonary Hypertension during Long-Term Follow-Up.

(1) Background: Pulmonary hypertension after aortic valve replacement (AVR; post-AVR PH) carries a poor prognosis. We assessed the pre-AVR hemodynamic characteristics of patients with versus without post-AVR PH. (2) Methods: We studied 205 patients (mean age 75 ± 10 years) with severe AS (indexed aortic valve area 0.42 ± 0.12 cm2/m2, left ventricular ejection fraction 58 ± 11%) undergoing right heart catheterization (RHC) prior to surgical (70%) or transcatheter (30%) AVR. Echocardiography to assess post-AVR PH, defined as estimated systolic pulmonary artery pressure > 45 mmHg, was performed after a median follow-up of 15 months. (3) Results: There were 83/205 (40%) patients with pre-AVR PH (defined as mean pulmonary artery pressure (mPAP) ≥ 25 mmHg by RHC), and 24/205 patients (12%) had post-AVR PH (by echocardiography). Among the patients with post-AVR PH, 21/24 (88%) had already had pre-AVR PH. Despite similar indexed aortic valve area, patients with post-AVR PH had higher mPAP, mean pulmonary artery wedge pressure (mPAWP) and pulmonary vascular resistance (PVR), and lower pulmonary artery capacitance (PAC) than patients without. (4) Conclusions: Patients presenting with PH roughly one year post-AVR already had worse hemodynamic profiles in the pre-AVR RHC compared to those without, being characterized by higher mPAP, mPAWP, and PVR, and lower PAC despite similar AS severity.

Pulmonary Hypertension in Patients With Heart Failure With Mid-Range Ejection Fraction.

Pulmonary hypertension (PH) is common in patients with heart failure (HF). The role of PH in patients with HF with reduced (HFrEF) and preserved (HFpEF) left ventricular ejection fraction (LVEF) has been extensively characterized during the last years. In contrast, the pathophysiology of HF with mid-range LVEF (HFmrEF), and in particular the role of PH in this context, are largely unknown. There is a paucity of data in this field, and the prevalence of PH, the underlying mechanisms, and the optimal therapy are not well-defined. Although often studied together there is increasing evidence that despite similarities with both HFrEF and HFpEF, HFmrEF also differs from both entities. The present review provides a summary of the current concepts of the mechanisms and clinical impact of PH in patients with HFmrEF, a proposal for the non-invasive and invasive diagnostic approach required to define the pathophysiology of PH and its management, and a discussion of future directions based on insights from mechanistic studies and randomized trials. We also provide an outlook regarding gaps in evidence, future clinical challenges, and research opportunities.

Corrected QT Interval in Severe Aortic Stenosis: Clinical and Hemodynamic Correlates and Prognostic Impact.

BACKGROUND: The role of the electrocardiogram for risk stratification in patients with severe aortic stenosis is not established. We assessed the hemodynamic correlates and the prognostic value of the corrected QT interval (QTc) in patients with severe aortic stenosis undergoing aortic valve replacement. METHODS: The QT interval was measured in a 12-lead electrocardiogram in 485 patients (age 74 ± 10 years, 57% male) with severe aortic stenosis (indexed aortic valve area 0.41 ± 0.13 cm2/m2, left ventricular ejection fraction 58 ± 12%) the day prior to cardiac catheterization. Prolonged QTc was defined as QTc >450 ms in men and QTc >470 ms in women. The outcome parameter was all-cause mortality. RESULTS: Patients with prolonged QTc (n = 100; 77 men, 23 women) had similar indexed aortic valve area but larger left ventricular and left atrial size, lower left ventricular ejection fraction, more severe mitral regurgitation, lower cardiac index, and higher mean pulmonary artery pressure, mean pulmonary artery wedge pressure, and pulmonary vascular resistance, as compared with patients with normal QTc (n = 385). After a median follow-up of 3.7 years (interquartile range, 2.6-5.2) after surgical (n = 349) or transcatheter (n = 136) aortic valve replacement, patients with prolonged QTc had higher mortality than those with normal QTc (hazard ratio 2.81 [95% confidence interval, 1.51-5.20]; P < .001). Prolonged QTc was an independent predictor of death along with more severe mitral regurgitation and higher pulmonary vascular resistance. CONCLUSIONS: In patients with severe aortic stenosis, prolonged QTc is a marker of an advanced disease stage associated with an adverse hemodynamic profile and increased long-term mortality after aortic valve replacement.

Invasive Hemodynamic Staging Classification of Cardiac Damage in Patients With Aortic Stenosis Undergoing Valve Replacement.

BACKGROUND: An echocardiographic 5-stage classification of cardiac damage in aortic stenosis (AS) has been shown to provide prognostic information. We aimed to create an analogous classification based on invasive hemodynamics. METHODS: We studied 421 patients (age 75 ± 10 years, 59% men) with severe AS with complete invasive hemodynamics obtained before aortic valve replacement (AVR). Cardiac damage stages were defined as follows: stage 0, absence of any of the following criteria; stage 1, left-ventricular end-diastolic pressure >15 mm Hg; stage 2, mean pulmonary artery wedge pressure > 15 mm Hg; stage 3, pulmonary vascular resistance > 3 Wood units and/or systolic pulmonary artery pressure > 60 mm Hg; stage 4, mean right atrial pressure >15 mm Hg. Patients were hierarchically classified in a given stage (worst stage) if the criterion was met for that stage. RESULTS: Sixty-seven (16%) patients were classified as stage 0, 113 (27%) as stage 1, 151 (36%) as stage 2, 73 (17%) as stage 3, and 17 (4%) as stage 4. After a median (interquartile range) follow-up of 3.8 (2.7 to 5.2) years after AVR, mortality was highest in stage 4 (hazard ratio; 95% confidence interval: 6.17 (1.74-21.89) vs stage 0; P = 0.005 and stage 3 patients (hazard ratio; 95% confidence interval: 4.17 (1.39-12.49) vs stage 0; P = 0.01,whereas mortality did not differ between patients in stages 0 to 2. CONCLUSIONS: A staging system of cardiac damage based on invasive hemodynamic parameters in patients with severe AS undergoing AVR predicts mortality. Pulmonary vascular disease and high right-atrial pressure are the major drivers of mortality.

Hemodynamic profile of patients with severe aortic valve stenosis and atrial fibrillation versus sinus rhythm.

BACKGROUND: In patients with severe aortic stenosis (AS), atrial fibrillation (AF) is associated with increased long-term mortality after aortic valve replacement (AVR), which may be due to unfavorable hemodynamics in AF. We aimed to analyze the hemodynamic profile of patients with severe AS and AF versus sinus rhythm (SR). METHODS: We performed cardiac catheterization in 486 patients (age 74 ±â€¯10 years, 58% males) with severe AS [indexed aortic valve area 0.41 ±â€¯0.13 cm2, left ventricular ejection fraction 58 ±â€¯12%]: 50 patients had AF, and 436 patients had SR. All patients underwent surgical (n = 350) or transcatheter (n = 136) AVR. RESULTS: Despite similar indexed aortic valve area (0.41 ±â€¯0.11 vs. 0.41 ±â€¯0.12 cm2/m2; p = 0.45) patients with AF had lower left ventricular ejection fraction, larger left atrial size, lower tricuspid annular plane systolic excursion, higher mean pulmonary artery pressure (34 ±â€¯13 vs. 24 ±â€¯9 mmHg), mean pulmonary artery wedge pressure (mPAWP; 22 ±â€¯8 vs. 15 ±â€¯7 mmHg), and pulmonary vascular resistance (2.8 ±â€¯1.9 vs. 2.0 ±â€¯1.3 Wood units) and lower stroke volume index (26 ±â€¯9 vs. 37 ±â€¯10 ml/m2) than patients with SR (p < 0.05 for all). Patients with AF and SR had a different mPAWP-left ventricular end-diastolic pressure (LVEDP) relationship with higher mPAWP in AF and higher LVEDP in SR. After a median follow-up of 49 (interquartile range, 35-64) months post-AVR patients with AF (p = 0.05) and patients with a larger difference between mPAWP and LVEDP (p = 0.005) had higher mortality. CONCLUSIONS: Patients with severe AS and concomitant AF have a distinct and significantly worse hemodynamic profile compared to patients with SR associated with worse clinical outcome.

Roadmap for the treatment of heart failure patients after hospital discharge: an interdisciplinary consensus paper.

The transition period from the hospital to the outpatient setting is a critical phase when managing heart failure. A well-structured transition is paramount and helps to ensure a tight follow-up schedule for the heart failure patient, thereby improving treatment outcomes. This article aims to provide guidance for the first three follow-up visits after hospital discharge, with a focus on monitoring heart failure patients and up-titrating their medication in primary care.

Relationship between B-type natriuretic peptide and invasive haemodynamics in patients with severe aortic valve stenosis.

AIMS: In patients with aortic stenosis (AS), B-type natriuretic peptide (BNP) is a prognostic marker. However, there is little information on the association between BNP and invasive haemodynamics in AS. The aim of the present study was to assess the hitherto not well-defined relationship between BNP and invasive haemodynamics in patients with severe AS undergoing aortic valve replacement (AVR) with a view to understand the link between high BNP and poor prognosis in these patients. In particular, we were interested in the association between BNP and combined pre-capillary and post-capillary pulmonary hypertension (CpcPH). METHODS AND RESULTS: BNP was measured in 252 patients (age 74 ± 10 years, 58% male patients) with severe AS [indexed aortic valve area 0.4 ± 0.1 cm2 /m2 and left ventricular ejection fraction (LVEF) 57 ± 12%] the day before cardiac catheterization. Patients were followed for a median (interquartile range) period of 3.1 (2.3-4.3) years after surgical (n = 157) or transcatheter (n = 95) AVR. The prevalence of CpcPH (mean pulmonary artery pressure ≥ 25 mmHg, mean pulmonary artery wedge pressure > 15 mmHg, and pulmonary vascular resistance > 3 Wood units) was 13%. The median BNP plasma concentration was 188 (78-452) ng/L. The indexed aortic valve area was similar across BNP quartiles (P = 0.21). Independent predictors of higher BNP (ln transformed) included lower haemoglobin (beta = -0.18; P < 0.001), lower LVEF (beta = -0.20; P < 0.001), more severe mitral regurgitation (beta = 0.20; P < 0.001), higher mean pulmonary artery wedge pressure (beta = -0.37; P < 0.001), and higher pulmonary vascular resistance (beta = 0.21; P < 0.001). In a multivariate model with CpcPH rather than its haemodynamic components, CpcPH was independently associated with higher BNP (0.21; P < 0.001). Higher ln BNP was associated with higher mortality [hazard ratio 1.90 (95% confidence interval 1.33-2.71); P < 0.001] in the univariate analysis. Patients in the third and fourth BNP quartiles had a more than six-fold risk of death compared with patients in the first and second quartiles [hazard ratio 6.29 (95% confidence interval 1.86-21.27); P = 0.003]. In the multivariate analysis, lower LVEF [hazard ratio 0.96 (95% confidence interval 0.94-0.99) per 1% increase; P = 0.01] and CpcPH [hazard ratio 4.58 (95% confidence interval 1.89-11.09); P = 0.001] but not BNP were independently associated with mortality. The areas under the receiver operator characteristics curve for BNP for the prediction of CpcPH and mortality were 0.88 and 0.74, respectively. CONCLUSIONS: In patients with severe AS, higher BNP is a marker of the presence of CpcPH and its contributors. The association between BNP and such an adverse haemodynamic profile at least in part explains the ability of BNP to predict long-term post-AVR mortality.

Non-invasive assessment prior to invasive coronary angiography in routine clinical practice in Switzerland - Is it according to the guidelines?

BACKGROUND: Non-invasive testing is recommended as a basis to decide about the indication for invasive coronary angiography (ICA) in patients with suspected stenotic coronary artery disease (CAD). However, a recent study based on insurance claims data reported that one third of patients undergoing ICA in Switzerland did not have non-invasive testing beforehand. We aimed to re-evaluate the practice of testing prior to ICA in Switzerland by manual review of patient histories. METHODS: Retrospective analysis of all 816 consecutive patients (age 67±9 years, 70% males) undergoing elective ICA solely for the evaluation of stenotic CAD during the year 2015 in a single center in Eastern Switzerland. The proportion of patients undergoing a non-invasive test was assessed, and predictors of the lack of such a test were determined. RESULTS: 764/816 (94%) patients had a non-invasive test prior to ICA. The majority of patients (728/816; 89%) had an exercise stress test, one fifth (160/816; 20%) underwent a test other than an exercise stress test (6% scintigraphy, 4% stress echocardiography, 6% stress magnetic resonance imaging, 4% computed tomography coronary angiography), and 122/816 (15%) patients had two tests. The use of antianginal drugs other than beta-blockers [odds ratio 1.92 (95% confidence interval 1.01-3.66); p = 0.047] and a lower left ventricular ejection fraction [odds ratio 0.97 (95% confidence interval 0.94-0.99) per one % point increase; p = 0.005] were independent predictors of the lack of a non-invasive test. ICA revealed stenotic CAD in 72% of patients, and 54% of patients underwent revascularization. Patients with and without non-invasive tests did not differ with respect to ICA findings and management. CONCLUSIONS: The present analysis suggests that patients are appropriately selected for ICA based on clinical judgement and non-invasive testing in Switzerland. There is no evidence for an overuse of ICA.

[Heart failure with preserved ejection fraction (HFpEF)]. / Herzinsuffizienz mit erhaltener linksventrikulärer Auswurffraktion (HFpEF).

Heart failure with preserved ejection fraction (HFpEF) Abstract. Heart failure with preserved left ventricular ejection fraction (HFpEF) is a very common form of heart failure typically seen in older patients and associated with poor prognosis. Patients with HFpEF are characterized by a s small left ventricle with concentric remodeling and abnormal compliance, which under the impact of additional cardiovascular mechanisms and non-cardiac comorbidities, leads to the cardinal symptoms of dyspnea and exercise intolerance. The diagnosis of HFpEF is still under debate, and the therapeutic options are limited despite intensive research efforts. In the present review article, we provide an overview of the current understanding of the pathiohysiology of HFpEF, the current diagnostic approach, and a summary of the available evidence on treatment.

Pulmonary Hypertension in Aortic and Mitral Valve Disease.

In patients with aortic and/or mitral valve disease the presence of pulmonary hypertension (PH) indicates a decompensated state of the disease with left ventricular and left atrial dysfunction and exhausted compensatory mechanism, i.e., a state of heart failure. Pulmonary hypertension in this context is the consequence of the backwards transmission of elevated left atrial pressure. In this form of PH, pulmonary vascular resistance is initially normal (isolated post-capillary PH). Depending on the extent and chronicity of left atrial pressure elevation additional pulmonary vascular remodeling may occur (combined pre- and post-capillary PH). Mechanical interventions for the correction of valve disease often but not always reduce pulmonary pressures. However, the reduction in pulmonary pressures is often modest, and persistent PH in these patients is common and a marker of poor prognosis. In the present review we discuss the pathophysiology and clinical impact of PH in patients with aortic and mitral valve disease, the comprehensive non-invasive and invasive diagnostic approach required to define treatment of PH, and recent insights from mechanistic studies, registries and randomized studies, and we provide an outlook regarding gaps in evidence, future clinical challenges, and research opportunities in this setting.

Diastolic stress echocardiography in the young: a study in nonathletic and endurance-trained healthy subjects.

BACKGROUND: The response of diastolic Doppler indices to exercise is not well defined for young subjects. The aims of this study were to evaluate this in nonathletic and endurance-trained probands and to correlate echocardiographic data with maximal oxygen consumption. METHODS: In this prospective study, Doppler echocardiography was performed at rest and after exercise in 40 nonathletes (NAs) and 20 endurance-trained athletes (ETs) aged < 40 years, matched for age and gender. Diastolic function was assessed by mitral inflow and early diastolic velocities of the septal (e' septal) and lateral (e' lateral) mitral annulus. Maximal oxygen consumption quantification was performed simultaneously. RESULTS: All cardiac chambers were larger in ETs than NAs. ETs had higher e' lateral at rest (18.1 ± 2.7 vs 16.3 ± 3.3 cm/sec, P = .02) and higher mitral E (141 ± 15 vs 132 ± 15 cm/sec, P = .02) and e' lateral (23.5 ± 2.5 vs 21.4 ± 3.0 cm/sec, P = .01) with exercise than NAs. There was a slight increase in E/e' septal (overall, from 6.8 ± 1.3 to 7.2 ± 1.2; P = .02) and E/e' lateral (overall, from 5.0 ± 0.8 to 6.2 ± 0.9; P < .0001) with exercise. Changes in diastolic parameters with exercise were similar in ETs and NAs. Percentage of predicted maximal oxygen consumption was correlated with exertional E (r = 0.28, P = .03) and e' lateral (r = 0.32, P = .01), but the strongest predictor was indexed left ventricular end-diastolic volume (r = 0.66, P < .0001). CONCLUSIONS: During exercise, E/e' increases but remains within normal ranges in healthy young subjects, and the response to exercise does not differ between ETs and NAs. These data help define the normal diastolic stress echocardiographic response in the young. Exercise capacity shows a correlation with enhanced exertional early diastolic velocities but is more closely related to cardiac structural adaption to endurance training.