Aim
Persistent symptoms despite guideline‐directed medical therapy (GDMT) and poor tolerance of GDMT are hallmarks of patients with advanced heart failure (HF) with reduced ejection fraction (HFrEF). ...However, real‐world data on GDMT use, dose, and prognostic implications are lacking.
Methods and results
We included 699 consecutive patients with HFrEF and at least one ‘I NEED HELP’ marker for advanced HF enrolled in a multicentre registry. Beta‐blockers (BB) were administered to 574 (82%) patients, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor–neprilysin inhibitors (ACEi/ARB/ARNI) were administered to 381 (55%) patients and 416 (60%) received mineralocorticoid receptor antagonists (MRA). Overall, ≥50% of target doses were reached in 41%, 22%, and 56% of the patients on BB, ACEi/ARB/ARNI and MRA, respectively. Hypotension, bradycardia, kidney dysfunction and hyperkalaemia were the main causes of underprescription and/or underdosing, but up to a half of the patients did not receive target doses for unknown causes (51%, 41%, and 55% for BB, ACEi/ARB/ARNI and MRA, respectively). The proportions of patients receiving BB and ACEi/ARB/ARNI were lower among those fulfilling the 2018 HFA‐ESC criteria for advanced HF. Treatment with BB and ACEi/ARB/ARNI were associated with a lower risk of death or HF hospitalizations (adjusted hazard ratio HR 0.63, 95% confidence interval CI 0.48–0.84, and HR 0.74, 95% CI 0.58–0.95, respectively).
Conclusions
In a large, real‐world, contemporary cohort of patients with severe HFrEF, with at least one marker for advanced HF, prescription and uptitration of GDMT remained limited. A significant proportion of patients were undertreated due to unknown reasons suggesting a potential role of clinical inertia either by the prescribing healthcare professional or by the patient. Treatment with BB and ACEi/ARB/ARNI was associated with lower mortality/morbidity.
Rates of guideline‐directed medical therapy (GDMT) prescription in real‐world patients with severe heart failure (HF) with reduced ejection fraction (HFrEF), reasons for underdosing and association with outcome. Upper left panel: rates of GDMT prescription and dosing, including beta‐blockers, angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitors (ACEi/ARB/ARNI) and mineralocorticoid receptor antagonists (MRA). Upper right panel: reasons for underdosing of beta‐blockers, ACEi/ARB/ARNI and MRA. Lower panels: Kaplan–Meier curves for 1‐year all‐cause death or HF hospitalization according to beta‐blockers, ACEi/ARB/ARNI and MRA prescription and dosing.
In patients with advanced heart failure (HF), defined according to the presence of at least one I-NEED-HELP criterium, the updated 2018 Heart Failure Association of the European Society of Cardiology ...(HFA-ESC) criteria for advanced HF identify a subgroup of patients with HF with worse prognosis, but whether ischemic etiology has a relevant prognostic impact in this very high-risk cohort is unknown. Patients from the HELP-HF registry were stratified according to ischemic etiology and presence of advanced HF based on 2018 HFA-ESC criteria. The primary end point was a composite of all-cause death and HF hospitalization at 1 year. Secondary end points were all-cause death, HF hospitalization, and cardiovascular death at 1 year. Ischemic etiology was a leading cause of HF, in both patients with advanced and nonadvanced HF (46.1% and 42.4%, respectively, p = 0.337). The risk of the primary end point (hazard ratio HR 1.31, 95% confidence interval CI 1.09 to 1.58) and all-cause mortality (HR 1.37, 95% CI 1.06 to 1.76) was increased in ischemic as compared with nonischemic patients. The risk of the primary end point was consistently higher in ischemic patients in both patients with advanced and nonadvanced HF (advanced HF, HR 1.50 95% CI 1.04 to 2.16; nonadvanced HF, HR 1.25 95% CI 1.01 to 1.56, pinteraction = 0.333), driven by an increased risk of mortality, mainly because of cardiovascular causes. In conclusion, ischemic etiology is the most common cause of HF in patients with at least one I-NEED-HELP marker and with or without advanced HF as defined by the 2018 HFA-ESC definition. In both patients with advanced and not-advanced HF, ischemic etiology carried an increased risk of worse prognosis.
Aims
Frailty is highly prevalent in patients with heart failure (HF), but a concordant definition of this condition is lacking. The Heart Failure Association of the European Society of Cardiology ...(HFA‐ESC) proposed in 2019 a new multi‐domain definition of frailty, but it has never been validated.
Methods and results
Patients from the HELP‐HF registry were stratified according to the number of HFA‐ESC frailty domains fulfilled and to the cumulative deficits frailty index (FI) quintiles. Prevalence of frailty and of each domain was reported, as well as the rate of the composite of all‐cause death and HF hospitalization, its single components, and cardiovascular death in each group and quintile. Among 854 included patients, 37 (4.3%), 206 (24.1%), 365 (42.8%), 217 (25.4%), and 29 (3.4%) patients fulfilled zero, one, two, three, or four domains, respectively, while 179 patients had a FI < 0.21 and were considered not frail. The 1‐year risk of adverse events increased proportionally to the number of domains fulfilled (for each criterion increase, all‐cause death or HF hospitalization: hazard ratio HR 1.43, 95% confidence interval CI 1.27–1.62; all‐cause death: HR 1.72, 95% CI 1.46–2.02, HF hospitalizations: subHR 1.21, 95% CI 1.04–1.31; cardiovascular death: HR 1.77, 95% CI 1.45–2.15). Consistent results were found stratifying the cohort for FI quintiles. The FI as a continuous variable demonstrated higher discriminative ability than the number of domains fulfilled (area under the curve = 0.68 vs. 0.64, p = 0.004).
Conclusion
Frailty in patients at risk for advanced HF, assessed via a multi‐domain approach and the FI, is highly prevalent and identifies those at increased risk of adverse events. The FI was found to be slightly more effective in identifying patients at increased risk of mortality.
Frailty in patients at risk of advanced heart failure. AUC, area under the curve; HFA‐ESC, Heart Failure Association of the European Society of Cardiology.
Clinical evaluation of central venous pressure is difficult, depends on experience, and is often inaccurate in patients with chronic advanced heart failure. We assessed the ultrasound-assessed ...internal jugular vein (JV) distensibility by ultrasound as a noninvasive tool to identify patients with normal right atrial pressure (RAP ≤7 mm Hg) in this population.
We measured JV distensibility as the Valsalva-to-rest ratio of the vein diameter in a calibration cohort (N=100) and a validation cohort (N=101) of consecutive patients with chronic heart failure with reduced ejection fraction who underwent pulmonary artery catheterization for advanced heart failure therapies workup.
A JV distensibility threshold of 1.6 was identified as the most accurate to discriminate between patients with RAP ≤7 versus >7 mm Hg (area under the receiver operating characteristic curve, 0.74 95% CI, 0.64-0.84) and confirmed in the validation cohort (receiver operating characteristic, 0.82 95% CI, 0.73-0.92). A JV distensibility ratio >1.6 had predictive positive values of 0.86 and 0.94, respectively, to identify patients with RAP ≤7 mm Hg in the calibration and validation cohorts. Compared with patients from the calibration cohort with a high JV distensibility ratio (>1.6; n=42; median RAP, 4 mm Hg; pulmonary capillary wedge pressure, 11 mm Hg), those with a low JV distensibility ratio (≤1.6; n=58; median RAP, 8 mm Hg; pulmonary capillary wedge pressure, 22 mm Hg;
<0.0001 for both) were more likely to die or undergo a left ventricular assist device implant or heart transplantation (event rate at 2 years: 42.7% versus 18.2%; log-rank
=0.034).
Ultrasound-assessed JV distensibility identifies patients with chronic advanced heart failure with normal RAP and better outcomes.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03874312.
To evaluate the role of tricuspid regurgitation in advanced heart failure.
The multicenter observational HELP-HF registry enrolled consecutive patients with heart failure and at least one 'I NEED ...HELP' criterion evaluated at four Italian centers between January 2020 and November 2021. Patients with no data on tricuspid regurgitation and/or receiving tricuspid valve intervention during follow-up were excluded. The population was stratified by no/mild tricuspid regurgitation vs. moderate tricuspid regurgitation vs. severe tricuspid regurgitation. Variables independently associated with tricuspid regurgitation, as well as the association between tricuspid regurgitation and clinical outcomes were investigated. The primary outcome was all-cause mortality.
Among the 1085 patients included in this study, 508 (46.8%) had no/mild tricuspid regurgitation, 373 (34.4%) had moderate tricuspid regurgitation and 204 (18.8%) had severe tricuspid regurgitation. History of atrial fibrillation, any prior valve surgery, high dose of furosemide, preserved left ventricular ejection fraction, moderate/severe mitral regurgitation and pulmonary hypertension were found to be independently associated with an increased likelihood of severe tricuspid regurgitation. Estimated rates of 1-year all-cause death were of 21.4, 24.5 and 37.1% in no/mild tricuspid regurgitation, moderate tricuspid regurgitation and severe tricuspid regurgitation, respectively (log-rank P < 0.001). As compared with nonsevere tricuspid regurgitation, severe tricuspid regurgitation was independently associated with a higher risk of all-cause mortality (adjusted hazard ratio 1.38, 95% confidence interval 1.01-1.88, P = 0.042), whereas moderate tricuspid regurgitation did not.
In a contemporary, real-world cohort of patients with advanced heart failure, several clinical and echocardiographic characteristics are associated with an increased likelihood of severe tricuspid regurgitation. Patients with severe tricuspid regurgitation have an increased risk of mortality.
Abstract
Aims
Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis, which could potentially affect any organ system. However, there have only been a few reports on cardiac ...involvement. In fact, it most commonly involves the sinuses, lungs, and kidneys with necrotizing granulomatous vasculitis. In 12% of a large series of patients with GPA there was cardiac involvement, largely manifested by pericarditis and coronary arteritis.
Methods and results
We describe a rare case of a 23-year-old girl, with no pathological history, at exception of a recent flu-like syndrome for which she carried out the search for SARS-CoV-2 RNA through nasopharyngeal swab, results negative. After a month, she went to the emergency department for a syncopal episode and subsequent head trauma. On this occasion, echocardiogram performed showed the presence of left ventricular systolic dysfunction due to hypokinesia of the middle distal segments; CT angiography of the chest revealed the presence of pulmonary embolism. For this reason, the patient was admitted to the cardiac intensive care unit, where EKG shown anterolateral myocardial infarction with ST elevation and immediately was performed coronary angiography, that evidenced two-vessel disease, with subsequent ineffective attempt to angioplasty. Due to the intercurrent appearance of hyposthenia and paraesthesia in the left upper limb, CT angiography of the brain was performed with detection of lower right pre central frontal hypodensity, suspected for recent ischaemic lesion and hypodensity of the right carotid artery as recent thrombosis. In light of the multi-organ involvement of ischaemic nature and the young age of the patient, rheumatological evaluation was carried out, with execution of a laboratory tests that showed the presence of positivity for ANCA anti-PR3 antibodies, on the basis of which was diagnosed GPA, and rituximab therapy was immediately initiated, with clinical benefit.
Conclusions
Cardiac involvement of GPA was first reported by Wegener in 1936. Classical or generalized GPA is characterized by necrotizing granulomatous vasculitis of the upper and lower respiratory tract together with glomerulonephritis. Widespread disseminated vasculitis involving both small arteries and veins occurs to a greater or lesser degree as the disease progresses. A localized form of GPA limited primarily to the upper and lower respiratory tracts has been described. Despite histopathological diagnosis of GPA, with autoantibodies against to circulatory neutrophilic cytoplasmic antigens, we can diagnose GPA easily and early. GPA must be kept in mind as the differential diagnosis of new onset cardiomyopathy, especially in the existence of pulmonary and renal pathologies. The clinical presentation of GPA can be so diverse that the list of differential diagnoses is vast, ranging from infections (fungal, bacterial, and mycobacterial) to other vasculitides, including Henoch–Schönlein purpura, sarcoidosis, Behcet syndrome, and malignancies. Despite that involving the heart is well described, significant cardiac complications occurring during the course of the disease are rare.
Abstract
Aims
In patients with chronic advanced heart failure (HF) signs of congestion are not always evident on clinical examination. We aim to validate the ultrasound (US)-assessed jugular vein ...distensibility (JVD), as a non-invasive tool to identify patients with normal right atrial pressure (RAP≤7 mmHg).
Methods and Results
In a single-center prospective study, we assessed chronic HF patients with a left ventricular ejection fraction (LVEF)<50% who underwent a pulmonary artery catheterization in the setting of advanced HF therapies workup. We first identify the JVD threshold (Valsalva/rest ratio of the vein diameter) of 1.6 that allowed the most accurate discrimination between patients with RAP≤7 vs. >7 mmHg (area under the curve AUC of 0.74; p<0.0001) in a calibration cohort of 100 patients (mean age 53 years, median LVEF 25%). Based on this JVD threshold, we defined patients with low JVD (≤1.6; n=58; median RAP 8 mmHg) and high JVD (>1.6, n=42; median RAP 4 mmHg). Then, we tested the threshold in 101 patients (validation cohort), where we found comparable results (AUC of 0.82; p<0.0001). The JVD threshold had 0.86 and 0.94 predictive positive values to identify patients with RAP≤7 mmHg in the calibration and validation cohorts. Finally, the low JVD vs. high JVD group had a 42.7% vs. 16.1% incidence of major cardiac events at 2 years (log-rank p=0.006), showing its prognostic value.
Conclusion
US-assessed JVD is an accurate diagnostic tool to identify advanced HF patients with normal RAP. This tool could be tested in the ambulatory setting to modulate diuretic/vasodilator therapies.
Abstract
Aims
An increasing number of patients with heart failure (HF) progresses to an advanced stage, characterized by persistent and sever symptoms and worse prognosis. A detailed characterization ...of patients with advanced HF is needed to optimize clinical management and timely refer for heart transplant or left ventricular assist device implantation.
Methods and results
A retrospective analysis was performed on patients with HF who were admitted to hospital or performed an outpatient visit at our centre (Spedali Civili di Brescia, Brescia, Italy) from 1 January 2020 to 31 December 2020, and who had at least one of the following high-risk characteristics: (1) previous or ongoing requirement for inotropes; (2) persisting New York Heart Association (NYHA) class III or IV and/or persistently high natriuretic peptides (BNP or NT-proBNP); (3) end-organ dysfunction, defined as worsening renal or liver dysfunction in the setting of HF; (4) ejection fraction (EF) <20%; (5) recurrent appropriate defibrillator shocks; (6) more than 1 hospitalization for HF in the last year; (7) persisting fluid overload and/or increasing diuretic requirement; (8) consistently low blood pressure (systolic blood pressure <90–100 mmHg); and (9) inability to up-titrate or need to decrease/cease HF therapies, such as beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor-neprilysin inhibitors, or mineralocorticoid receptor antagonists. The updated 2018 Heart Failure Association (HFA)—European Society of Cardiology (ESC) criteria for defining advanced HF were evaluated. The primary endpoint was all-cause mortality; secondary endpoints were a composite of all-cause mortality or hospitalization for HF and a composite of all-cause mortality or hospitalization for any reason. Among 493 patients with HF who were hospitalized or performed an outpatient visit in 2020, 230 (46.7%) had at least one high risk criterion and were included in the study. Mean age was 75.5 ± 11.9 years, 156 patients (67.8%) were men, and 160 patients (69.6%) were hospitalized and included as inpatients. Median EF was 38% interquartile range (IQR): 25–50% and 117 patients (50.9%) had HF with reduced EF (<40%); median NT-proBNP was 4044 (IQR: 2262–7664) pg/mL. Among the included 230 patients, 38 (16.5%) had all four updated HFA-ESC criteria defining advanced HF, 53 (23.0%) had American College of Cardiology (ACC)/American Heart Association (AHA) stage D, 21 (9.1%) had INTERMACS profile 1–3. In-hospital mortality was 10.6% (among inpatients). After a median follow-up of 301 (214–442) days, a total of 62 patients died (27.0%), and the secondary endpoints of all-cause death or HF hospitalization and all-cause death or any hospitalization were observed in 107 (46.5%) and 139 (60.4%) patients, respectively. Patients fulfilling all four updated HFA-ESC criteria for advanced HF had a higher risk of all-cause mortality (unadjusted HR: 2.06; 95% CI: 1.18–3.60; P = 0.011), also after adjustment for covariates of interest (adjusted HR: 2.20; 95% CI: 1.03, 4.70; P = 0.041).
Conclusions
In our contemporary, real-world cohort of HF patients with high-risk characteristics, mid-term prognosis was poor, and the use of updated HFA-ESC criteria defining advanced HF identified a subset at increased risk of mortality.
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