[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.

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.

Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure: The GALACTIC Randomized Clinical Trial.

Importance: Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF). Objective: To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF. Design, Setting, and Participants: Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019. Interventions: Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days. Results: Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, -3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39]; P = .59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%). Conclusions and Relevance: Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days. Trial Registration: ClinicalTrials.gov Identifier: NCT00512759.

Coronary angiography with or without percutaneous coronary intervention in patients with hemophilia-Systematic review.

OBJECTIVES: We aimed to summarize the evidence for periprocedural and long-term strategies to both minimize the bleeding risk and ensure sufficient anticoagulation and antiaggregation in hemophilia patients undergoing coronary angiography with or without percutaneous coronary interventions (PCI). BACKGROUND: Hemophilia patients undergoing coronary angiography and PCI are at risk of bleeding due to deficiency of the essential clotting factors VIII or IX combined with the need of peri-interventional anticoagulation and antiaggregation and dual antiplatelet therapy (DAPT) after PCI. METHODS: We report on a patient with moderate hemophilia B undergoing single-vessel PCI with administration of factor IX concentrate during the procedure and during the 1-month DAPT period. In addition, a systematic review of patients (n = 54, mean age 58 ± 10 years) with hemophilia A (n = 45, 83%) or B (n = 9, 17%) undergoing coronary angiography with or without PCI is presented. RESULTS: Peri-interventional factor substitution was performed in the majority (42 of 54, 78%) but not all patients. In 38 of 54 (70%) patients undergoing coronary angiography, PCI with balloon dilation (n = 5), bare metal (n = 31), or drug-eluting stents (n = 2) was performed. For PCI unfractioned heparin (n = 24), low molecular weight heparin (n = 2), bivalirudin (n = 4), or no periprocedural anticoagulation at all (n = 8) were used. PCI was successful in all cases. After stenting, the majority (28 of 33; 85%) was treated with DAPT (median duration 1 month). Major periprocedural bleeding episodes occurred in 3 of 54 (6%) patients. Bleeding during follow-up occurred in 11 of 54 (20%) patients. CONCLUSIONS: Coronary angiography and PCI in patients with hemophilia are effective and safe when applying individualized measures to prevent bleeding.

Inverse Association Between Myocardial B-Type Natriuretic Peptide Release and Functional Capacity in Healthy Humans.

BACKGROUND: B-type natriuretic peptide (BNP) has been found to be inversely related to peak oxygen consumption (peak VO2) in various patient populations. However, in these studies, circulating plasma BNP, i.e. the net effect of release and elimination, rather than cardiac BNP release has been measured. We assessed the relationship between the transcardiac BNP gradient [ΔBNPCS-A, i.e. the difference between BNP in coronary sinus (BNPCS) and arterial (BNPA) plasma] and peak VO2 in healthy subjects with a view to better understanding the regulation of cardiac BNP release in humans. METHODS: We studied 10 asymptomatic subjects (age 64±11 years, two females) with preserved left ventricular function (left ventricular ejection fraction 62±5%, averaged early diastolic mitral annular velocity 9±3cm/s) and low BNP (BNP in venous plasma [BNPV] <100ng/l). Subjects underwent measurement of BNPA and BNPCS for the calculation of ΔBNPCS-A, maximal cardiopulmonary exercise testing, echocardiography and resting and submaximal exercise right heart catheterisation. RESULTS: The median (range) BNPV, BNPA, BNPCS, and ΔBNPCS-A were 62 (14, 82), 60 (13, 79), 110 (25, 157), and 44 (1, 103) ng/l. The median peak VO2 during cardiopulmonary exercise testing was 21.5 (18, 54) ml/min/kg. There was an inverse correlation between higher ΔBNPCS-A and lower peak VO2 (r=-0.84; p=0.002) and oxygen pulse (r=-0.64, p=0.049). There was a trend towards an inverse correlation between ΔBNPCS-A and the exercise arteriovenous oxygen content difference (r=-0.58; p=0.08). CONCLUSIONS: In healthy humans, there is an inverse association between myocardial BNP release and peak VO2, which may be due to cardiac and non-cardiac mechanisms.

[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.

N-Terminal Pro-B-Type Natriuretic Peptide-Guided Therapy in Chronic Heart Failure Reduces Repeated Hospitalizations-Results From TIME-CHF.

BACKGROUND: Although heart failure (HF) patients are known to experience repeated hospitalizations, most studies evaluated only time to first event. N-Terminal B-type natriuretic peptide (NT-proBNP)-guided therapy has not convincingly been shown to improve HF-specific outcomes, and effects on recurrent all-cause hospitalization are uncertain. Therefore, we investigated the effect of NT-proBNP-guided therapy on recurrent events in HF with the use of a time-between-events approach in a hypothesis-generating analysis. METHODS AND RESULTS: The Trial of Intensified Versus Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized 499 HF patients, aged ≥60 years, left ventricular ejection fraction ≤45%, New York Heart Association functional class ≥I,I to NT-proBNP-guided versus symptom-guided therapy for 18 months, with further follow-up for 5.5 years. The effect of NT-proBNP-guided therapy on recurrent HF-related and all-cause hospitalizations and/or all-cause death was explored. One hundred four patients (49 NT-proBNP-guided, 55 symptom-guided) experienced 1 and 275 patients (133 NT-proBNP-guided, 142 symptom-guided) experienced ≥2 all-cause hospitalization events. Regarding HF hospitalization, 132 patients (57 NT-proBNP-guided, 75 symptom-guided) experienced 1 and 122 patients (57 NT-proBNP-guided, 65 symptom-guided) experienced ≥2 events. NT-proBNP-guided therapy was significant in preventing 2nd all-cause hospitalizations (hazard ratio [HR] 0.83; P = .01), in contrast to nonsignificant results in preventing 1st all-cause hospitalization events (HR 0.91; P = .35). This was not the case regarding HF hospitalization events (HR 0.85 [P = .14] vs HR 0.73 [P = .01]) The beneficial effect of NT-proBNP-guided therapy was seen only in patients aged <75 years, and not in those aged ≥75 years (interaction terms with P = .01 and P = .03 for all-cause hospitalization and HF hospitalization events, respectively). CONCLUSION: NT-proBNP-guided therapy reduces the risk of recurrent events in patients <75 years of age. This included all-cause hospitalization by mainly reducing later events, adding knowledge to the neutral effect on this end point when shown using time-to-first-event analysis only. CLINICAL TRIAL REGISTRATION: isrctn.org, identifier: ISRCTN43596477.

Spontaneous Coronary Artery Dissection: Angiographic Follow-Up and Long-Term Clinical Outcome in a Predominantly Medically Treated Population.

OBJECTIVE: We sought to assess the angiographic and long-term clinical outcomes in a predominantly medically treated population with spontaneous coronary artery dissection (SCAD). BACKGROUND: There are little data on the angiographic and long-term outcome in patients with SCAD. METHODS: We studied 64 patients with SCAD (mean age 53 years, 94% females, three peripartum) with acute coronary syndrome who were treated using coronary bypass grafting (n = 1), percutaneous coronary intervention (n = 7), or medical therapy (n = 56). A repeat angiogram was performed in 40/64 (63%) patients. The median clinical follow-up was 4.5 years. RESULTS: Five (8%) patients had a major cardiac event. One patient with peripartum left main SCAD and cardiogenic shock died during PCI. One patient with conservatively treated SCAD of the posterior descending artery suffered out-of-hospital cardiac arrest 16 days after the initial angiogram but survived. Three patients experienced a second SCAD in another vessel 3.7, 4.7, and 7.9 years after the index event while the initial dissection had healed. Thirty medically treated patients underwent a scheduled repeat angiogram showing healing of the dissection in all but one patient. After a median follow-up of 4.5 (1.8-8.4) years, all 63 patients surviving the index event were alive and free of symptoms suggestive of myocardial ischemia. CONCLUSIONS: In general, the long-term outcome of patients with SCAD is excellent, and medical therapy can be safely applied in the majority of patients. However, SCAD can be a life-threatening and sometimes catastrophic event, and some patients experience early or late complications including SCAD of another vessel. © 2015 Wiley Periodicals, Inc.

Differential prognostic impact of resting heart rate in older compared with younger patients with chronic heart failure--insights from TIME-CHF.

BACKGROUND: There is little information regarding the prognostic role of resting heart rate (HR) in older compared with younger patients with chronic heart failure (HF). METHODS AND RESULTS: In patients enrolled in the Trial of Intensified Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) with sinus rhythm, effects of baseline HR (≥70 vs <70 beats/min [bpm]) on 18-month outcomes were compared between older (≥75 years; n = 186) and younger (<75 years; n = 141) patients. Older patients with lower (61 ± 6 bpm) and higher (83 ± 9 bpm) HR had similar left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and survival and HF hospitalization-free survival. In contrast, younger patients with higher HR (81 ± 7 bpm) had higher NT-proBNP and NYHA functional class, lower LVEF, and a higher risk of death (hazard ratio 4.01 [95% confidence interval (CI) 1.17 -13.69]; P = .02) and death or HF hospitalization (hazard ratio 2.35 [95% CI 1.01-5.50]; P = .04) than those with lower HR (62 ± 5 bpm), with the association between higher HR and survival remaining significant after adjustment for NYHA functional class, LVEF, and NT-proBNP. CONCLUSIONS: In contrast to HF patients aged <75 years, we found no association between HR and worse outcomes in HF patients aged ≥75 years.

Accuracy of Echocardiographic Cardiac Index Assessment in Subjects with Preserved Left Ventricular Ejection Fraction.

INTRODUCTION: We aimed to determine the accuracy of the echocardiographic assessment of cardiac index (CI) in subjects with preserved left ventricular ejection fraction (LVEF). METHODS: Thirty-three subjects with LVEF >50%, normal sinus rhythm, and a broad spectrum of hemodynamic profiles underwent echocardiography immediately followed by right heart catheterization. As gold standards, CI was assessed using thermodilution [CI (TD)] and the Fick method [CI (F)]. Echocardiographic CI was assessed by four methods: from the left ventricular outflow tract (LVOT) velocity time integral and the LVOT diameter as measured [CI (LVOTm)] as well as estimated from body surface area [CI (LVOTe)], and from stroke volume indices assessed using the biplane [CI (BP)] and monoplane [CI (MP)] methods. RESULTS: The mean CI (TD), CI (F), CI (LVOTm), CI (LVOTe), CI (BP), and CI (MP) were 3.0 ± 0.9, 3.1 ± 0.7, 2.8 ± 0.6, 3.3 ± 0.6, 2.0 ± 0.6, and 2.2 ± 0.7 L/min/m(2) . There were modest correlations between CI (TD) and CI (F) and all four noninvasive measures of CI with r(2) values ranging from 0.09 to 0.30. CI (LVOTm) underestimated CI (TD) and CI (F) by 0.3 and 0.3 L/min/m(2) , CI (LVOTe) overestimated CI (TD) and CI (F) by 0.3 and 0.2 L/min/m(2) , and CI (BP) and CI (MP) underestimated CI (TD) and CI (F) by 1.1 and 1.1 L/min/m(2) and 0.9 and 0.9 L/min/m(2) , respectively, with large limits of agreement for all comparisons. CONCLUSIONS: In subjects with nondilated left ventricles with preserved LVEF, flow- or volume-based measures of CI by 2D echocardiography may not accurately reflect CI (TD) and CI (F). Further larger studies are required to verify our findings and to evaluate the accuracy of contrast and 3D echocardiography in this setting.

Interaction between pulmonary hypertension and diastolic dysfunction in an elderly heart failure population.

BACKGROUND: Pulmonary hypertension due to left heart disease is very common. Our aim was to investigate the relationship of the severity of left ventricular diastolic dysfunction with precapillary and postcapillary pulmonary hypertension (PH) in an elderly heart failure (HF) population. METHODS AND RESULTS: A post hoc analysis of the Trial of Intensified Medical Therapy in Elderly Patients With Congestive Heart Failure data was done. Baseline transthoracic echocardiography was used to categorize diastolic function, estimate pulmonary artery pressure and pulmonary capillary wedge pressure, and calculate the transpulmonary pressure gradient (TPG). Among 392 HF patients, PH was present in 31% of patients with grade 1, in 37% of patients with grade 2, and in 65% of patients with grade 3 diastolic dysfunction; 54% of all HF patients with PH had a TPG >12 mm Hg, suggesting not only a postcapillary but also an additional precapillary component of PH. Survival was not related to the severity of diastolic dysfunction, but was worse in patients with PH (hazard ratio 1.63, 95% confidence interval 1.07-2.51; P = .024). CONCLUSIONS: Our data indicate that HF patients with even mild diastolic dysfunction often have PH. Echocardiographic assessment suggest that the presence of PH might not simply be due to increased PCWP, but in part due to a precapillary component.

Midregional pro-adrenomedullin and copeptin: exercise kinetics and association with the cardiopulmonary exercise response in comparison to B-type natriuretic peptide.

PURPOSE: Midregional pro-adrenomedullin (MR-proADM) and C-terminal pro-vasopressin (copeptin) are novel biomarkers providing prognostic information in various settings. We aimed to (1) assess the kinetics of MR-proADM and copeptin during cardiopulmonary exercise testing (CPET); (2) assess the relationship of MR-proADM and copeptin measured at rest with peak oxygen consumption (peak VO2) and other key CPET parameters; (3) compare this relationship to that of B-type natriuretic peptide (BNP). METHODS: In 162 patients undergoing symptom-limited CPET for evaluation of exercise intolerance, MR-proADM, copeptin, and BNP were measured at rest and peak exercise. RESULTS: There was a significant rise in copeptin and BNP (p < 0.001) but not in MR-proADM (p = 0.60) from rest to peak exercise. MR-proADM (r = -0.57; p < 0.001) and BNP (r = -0.49; p < 0.001) but not copeptin were significantly and inversely related to peak VO2. MR-proADM was inversely correlated to the percentage of predicted heart rate achieved and peak oxygen pulse and directly related to the peak ventilation/carbon dioxide production relationship, the physiological dead space-to-tidal volume ratio, and the alveolo-arterial oxygen gradient (p ≤ 0.01 for all), and these associations were at least as strong as for BNP. In contrast, copeptin was not significantly related to any of these parameters (p > 0.05 for all). CONCLUSION: In contrast to BNP and copeptin, MR-proADM is not immediately affected by a maximal exercise test. MR-proADM but not copeptin is at least as good an indicator of low peak VO2 and CPET parameters reflecting an impaired cardiac output reserve, ventilatory efficiency and diffusion capacity as BNP, and thereby a global cardiopulmonary stress marker.

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.

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.

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.

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.

End-of-life preferences of elderly patients with chronic heart failure.

AIMS: Elderly heart failure (HF) patients are assumed to prefer improved quality of life over longevity, but sufficient data are lacking. Therefore, we assessed the willingness to trade survival time for quality-of-life (QoL) and the preferences for resuscitation. METHODS AND RESULTS: At baseline and after 12 and 18 months, 622 HF patients aged ≥60 years (77 ± 8 years, 74% NYHA-class ≥III) participating in the Trial of Intensified vs. standard Medical therapy in Elderly patients with Congestive Heart Failure had prospective evaluation of end-of-life preferences by answering trade-off questions (willingness to accept a shorter life span in return for living without symptoms) and preferences for resuscitation if necessary. The time trade-off question was answered by 555 patients (89%), 74% of whom were not willing to trade survival time for improved QoL. This proportion increased over time (Month 12: 85%, Month 18: 87%, P < 0.001). In multivariable analysis, willingness to trade survival time increased with age, female sex, a reduced Duke Activity Status Index, Geriatric Depression Score, and history of gout, exercise intolerance, constipation and oedema, but even combining these variables did not result in reliable prediction. Of 603 (97%) patients expressing their resuscitation preference, 51% wished resuscitation, 39% did not, and 10% were undecided, with little changes over time. In 430 patients resuscitation orders were known; they differed from patients' preferences 32% of the time. End-of-life preferences were not correlated to 18-month outcome. CONCLUSION: Elderly HF patients are willing to address their end-of-life preferences. The majority prefers longevity over QoL and half wished resuscitation if necessary. Prediction of individual preferences was inaccurate.

Impact of N-acetylcysteine on endothelial function, B-type natriuretic peptide and renal function in patients with the cardiorenal syndrome: a pilot cross over randomised controlled trial.

BACKGROUND: Both heart and renal failure are characterised by increased systemic oxidative stress and endothelial dysfunction and occur in the cardiorenal syndrome (CRS). The aim of the present study was to assess the impact of N-acetylcysteine (NAC), a potent antioxidant, on endothelial function, B-type natriuretic peptide (BNP) and renal function in patients with CRS. METHODS: In a double blind, placebo controlled manner, we randomised nine stable outpatients with both heart failure (LVEF<40% and NYHA class II or III) and renal failure (Cockroft Gault clearance of 20-60ml/min) to placebo or NAC (500mg orally twice daily) for 28 days followed by a wash out period (>7 days) and crossover to the other treatment. RESULTS: Eight patients completed the study and all data (N=9) was used in the analysis. Mean forearm blood flow improved significantly with NAC with mean ratio of improvement of 1.99 (SEM: ±0.49) for NAC and 0.73 (SEM: ±0.23) for placebo with a p-value of 0.047. There was no significant difference in BNP (p=0.25), renal function (p=0.71) or NYHA class (p=0.5). No deaths occurred during the trial. CONCLUSION: In this pilot trial of patients with CRS, NAC therapy was associated with improved forearm blood flow. This may represent a general improvement in endothelial function and warrants further investigation of antioxidant therapy in these patients.