Academic Editor: Peter A. McCullough
The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented challenge.
Meeting this has resulted in changes to working practices and the impact on the
management of patients with heart failure with reduced ejection fraction (HFrEF)
is largely unknown. We performed a retrospective, observational study contrasting
patients diagnosed with HFrEF attending specialist heart failure clinics at a UK
hospital, whose subsequent period of optimisation of medical therapy was during
the COVID-19 pandemic, with patients diagnosed the previous year. The primary
outcome was the change in equivalent dosing of ramipril and bisoprolol at
6-months. Secondary outcomes were the number and type of follow-up consultations,
hospitalisation for heart failure and all-cause mortality. In total, 60 patients
were diagnosed with HFrEF between 1 December 2019 and 30 April 2020, compared to
54 during the same period of the previous year. The absolute number of
consultations was higher (390 vs 270; p = 0.69), driven by increases in
telephone consultations, with a reduction in appointments with hospital nurse
specialists. After 6-months, we observed lower equivalent dosing of ramipril (3.1
The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented challenge to healthcare systems. Meeting this has resulted in dramatic changes to working practices for those caring for patients with chronic diseases. The Leeds Integrated Heart Failure service comprises of physicians, heart failure nurse specialists and dedicated cardiac physiologists, combining hospital and community care. A principle aim of the service is optimising the delivery of guideline-directed medical therapy (GDMT) to improve outcomes for patients with heart failure [1].
The re-deployment of healthcare personnel, transition from face-to-face to telephone consultations and the wider impact of the COVID-19 pandemic on the management of patients with heart failure remains largely unknown. Here we report the changes in frequency and type of follow-up appointments, optimisation of GDMT and outcomes in newly diagnosed patients with heart failure with reduced ejection fraction (HFrEF) during the first wave of the pandemic.
We performed a retrospective, observational study in ambulatory patients with newly diagnosed HFrEF attending the Leeds Integrated Heart Failure Service, designed and reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.
We contrasted patients diagnosed with HFrEF between 1 December 2019 and 30 April
2020 whose diagnosis and subsequent period of dose optimisation of GDMT was
during the first wave of the COVID-19 pandemic, with patients diagnosed during
the same period the previous year. Inclusion required no previous diagnosis of
HFrEF, age
Study flow chart. Description: Inclusion and exclusion criteria of patients referred to the Leeds integrated heart failure service.
We recorded patient demographics, aetiology of heart failure, past medical
history, functional capacity according to New York Heart Associated (NYHA)
classification. Transthoracic echocardiogram was performed at the point of first
attendance at the integrated heart failure service and we measured LVEF according
to Simpson’s biplane method, left ventricular (LV) end-diastolic diameter, right
ventricular impairment and presence of regional wall motion abnormality according
to national recommendations [2]. We recorded dosing of guideline-directed medical
therapy at enrolment and at 6-months. We assessed the frequency and type of
follow-up consultations, outpatient blood tests, change in dosing of angiotensin
converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB),
The date of the first echocardiogram showing LVEF
Patients were followed up until death or 6-months following diagnosis. Outcomes data were obtained from the electronic Patient Pathway Manager Plus care record, which updates mortality events daily directly from the UK Office of National Statistics. The primary outcome was the change in equivalent dosing of ramipril and bisoprolol between the time of diagnosis and 6-months. Secondary outcomes were the number and type of follow-up consultations, hospitalisation for heart failure and all-cause mortality during the 6-month period following diagnosis.
All statistical analyses were performed using IBM SPSS Statistics version 26
(IBM Corporation, Armonk, NY, USA). Unless otherwise stated, continuous variables
are expressed as mean
A total 60 patients were newly diagnosed with HFrEF following referral to the
integrated heart failure service between 01 Dec 2019 and 30 April 2020, compared
to 54 during the same period in the previous year (Fig. 1). Patients had a mean
age of 74.7
All patients (n = 114) | COVID-19 (n = 60) | Previous year (n = 54) | p-value | ||
Demographics | |||||
Age (years) | 74.7 |
74.3 |
75.2 |
0.72 | |
Male sex [n (%)] | 70 (61.4) | 35 (58.2) | 35 (64.8) | 0.48 | |
Medical history | |||||
Ischaemic aetiology [n (%)] | 36 (32.4) | 15 (25.4) | 21 (40.4) | 0.093 | |
Hypertension [n (%)] | 61 (53.5) | 33 (55.0) | 28 (51.9) | 0.74 | |
Diabetes mellitus [n (%)] | 44 (38.6) | 20 (33.3) | 24 (44.4) | 0.22 | |
Atrial fibrillation [n (%)] | 47 (41.2) | 25 (41.7) | 22 (40.7) | 0.92 | |
Stroke [n (%)] | 11 (9.6) | 3 (5.0) | 8 (14.8) | 0.076 | |
Chronic kidney disease [n (%)] | 25 (21.9) | 12 (20.0) | 13 (24.1) | 0.60 | |
COPD [n (%)] | 14 (12.3) | 6 (14.8) | 8 (10.0) | 0.43 | |
NYHA class | |||||
I | 8 (7.0) | 6 (10.0) | 2 (3.7) | ||
II | 66 (57.9) | 36 (60.0) | 30 (55.6) | 0.27 | |
III | 40 (35.1) | 18 (30.0) | 22 (40.7) | ||
Blood tests | |||||
Haemoglobin (g/L) | 128.7 |
129.5 |
127.8 |
0.64 | |
Creatinine ( |
100.1 |
98.4 |
102.0 |
0.61 | |
Albumin (g/L) | 35.7 |
35.5 |
35.9 |
0.66 | |
HbA1c (mmol/mol) | 47.7 |
46.0 |
49.7 |
0.21 | |
NT-pro-BNP (ng/L) | 6577.9 |
6620.6 |
6526.1 |
0.95 | |
Electrocardiogram | |||||
Heart rate (beats/min) | 83.2 |
85.1 |
81.3 |
0.33 | |
QRS (ms) | 109.5 |
105.5 |
113.6 |
0.10 | |
PR (ms) | 181.1 |
174.4 |
188.8 |
0.19 | |
LBBB [n (%)] | 15 (13.5) | 7 (12.3) | 8 (14.8) | 0.46 | |
Echocardiogram | |||||
LVEF (%) | 33.1 |
33.8 |
32.4 |
0.54 | |
LVEDd (mm) | 54.4 |
53.1 |
56.1 |
0.13 | |
RV impairment [n (%)] | 57 (50.4) | 32 (54.2) | 25 (46.3) | 0.40 | |
RWMA [n (%)] | 70 (61.4) | 32 (53.3) | 38 (70.4) | 0.062 | |
Baseline medical therapy | |||||
Beta-blocker [n (%)] | 80 (70.2) | 42 (70.0) | 38 (70.4) | 0.97 | |
Bisoprolol dose (mg) | 3.5 |
3.2 |
3.8 |
0.35 | |
ACEi/ARB [n (%)] | 73 (64.0) | 36 (60.0) | 37 (68.5) | 0.34 | |
Ramipril dose ( mg) | 2.9 |
2.7 |
3.1 |
0.56 | |
Loop diuretic [n (%)] | 75 (65.8) | 42 (70.0) | 33 (61.1) | 0.32 | |
Furosemide dose (mg) | 38.0 |
40.7 |
35.0 |
0.54 | |
MRA [n (%)] | 24 (21.1) | 15 (25.0) | 9 (16.7) | 0.28 | |
Ivabradine | 5 (4.4) | 1 (1.7) | 4 (7.4) | 0.14 | |
SGLT2i [n (%)] | 12 (10.5) | 7 (11.7) | 5 (9.3) | 0.68 | |
Antiplatelet [n (%)] | 41 (36.0) | 20 (33.3) | 21 (38.9) | 0.54 | |
Anticoagulant [n (%)] | 34 (29.8) | 20 (33.3) | 14 (25.9) | 0.39 | |
COPD, chronic obstructive pulmonary disease; NYHA, New York Heart Association; HbA1c, glycosylated haemoglobin; NT-pro-BNP, N-terminal pro-brain natriuretic peptide; LBBB, left bundle branch block; LVEF, left ventricular ejection fraction; LVEDd, left ventricular end-diastolic diameter; RV, right ventricular; RWMA, regional wall motion abnormality; ACEi, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; MRA, mineralocorticoid receptor antagonist; SGLT2i, sodium-glucose co-transporter 2 inhibitor. |
In the first 6-months following diagnosis the absolute number of consultations
was higher during the COVID-19 pandemic (390 vs 270; p = 0.69) compared
to the previous year (Table 2). This was primarily driven by increases in the
number telephone consultations with community heart failure nurses (185 vs 53;
p = 0.008). However, the number of consultations with hospital heart
failure specialist nurses was less, no patients were seen face-to-face (28 vs 0;
p = 0.001) and only one had telephone follow-up (3 vs 1; p =
0.26) during the study period. Although the number of consultations with
physicians was similar, we observed a transition from face-to-face (76 vs 61;
p = 0.033), to telephone appointments (0 vs 21; p
COVID-19 | Previous year | p-value | |
Hospital nurse face-to-face | 0 | 28 | 0.001 |
Hospital nurse telephone | 1 | 3 | 0.26 |
Community nurse face-to-face | 122 | 110 | 0.50 |
Community nurse telephone | 185 | 53 | 0.008 |
Physician face-to-face | 61 | 76 | 0.003 |
Physician telephone | 21 | 0 |
Equivalent doses of ramipril (3.1
Plots of the change in equivalent dosing of ramipril and
bisoprolol between baseline and 6-months, excluding patients who were receiving
maximum licensed doses at baseline. Description: The change in dosing was lower for patients whose period of
dose optimisation was during the COVID-19 pandemic. * p
We observed no differences in the proportion of patients who died (5.0% vs 7.4%; p = 0.59) or were hospitalised with heart failure (13.3% vs 9.3%; p = 0.49) between study periods.
In this retrospective analysis of newly diagnosed patients with HFrEF referred to the Leeds Integrated Heart Failure Service, we observed that during the COVID-19 pandemic patients were more often managed by telephone consultations and the optimisation of GDMT, especially ACEi/ARB was less successful compared to the previous year.
Recent reports have highlighted that patients with HFrEF are at high-risk of severe disease from COVID-19 [3, 4], and that the pandemic has also resulted in significant disruption to heart failure service including the cancellation or postponement of appointments and investigations [5]. Additionally, reports have highlighted a reluctance to seek medical attention, with reduced attendances with worsening heart failure during the peak of the pandemic [6, 7]. However, the impact of the pandemic on the optimisation of GDMT is unknown.
In the UK, heart failure nurse specialists supervise the titration and optimisation of GDMT for patients proven to have HFrEF. The majority of these specialist nurses are independent prescribers and many have additional qualifications in advanced practice. In many regions, including ours, the pandemic resulted in the re-deployment of nurse specialists, especially those working in hospital settings away from heart failure services to manage the burden of COVID-19. Perhaps in response to this, the number of consultations with community heart failure nurse specialists increased, albeit with a transition to telephone consultations.
For patients with newly diagnosed HFrEF, the optimisation of GDMT was less
during the COVID-19 pandemic compared to the previous year, especially the
up-titration of inhibitors of the renin-angiotensin system, despite an overall
higher number of consultations. The reasons for this may firstly be due
to carers being less comfortable with dose escalation of medications which
usually require an assessment of blood pressure and kidney function between
dosing increments. Prior to the pandemic, usual practice was to require blood
tests for renal function after two weeks, with regular follow-up appointments to
titrate dosing according to blood pressure and heart rate. Whilst during the
pandemic, the majority of patients had access to blood pressure monitors
(provided by primary care or purchased), the access to routine blood testing was
reduced. Hence, given the more directly clinically obvious effects of
We have previously shown that even small increments in dosing of disease modifying therapies are associated with favourable outcomes in HFrEF [8]. We explored rates of heart failure hospitalisations and all-cause mortality, and although observed outcomes were similar, this might have been due to small numbers of patients a low event rate, and it is feasible that at a population level, the COVID-19 pandemic might have resulted in worse long-term outcomes for patients with HFrEF and this warrants further investigation. Another explanation might be due to a reluctance to seek medical attention, as evidenced by the lower rate of attendances for worsening heart failure observed during the COVID-19 pandemic [6, 9].
The principal limitations of this study are the small sample size and short duration of follow-up. Despite this, we were able to show a less successful optimisation of medical therapies during the COVID-19 pandemic. This study was conducted in a single centre in the UK, and so may not be generalisable to other healthcare systems. We included patients who had LVEF 40–49% who might be regarded as having heart failure with mid-range ejection fraction according to guidelines [1]. Despite there being less clear-cut evidence of benefit of medical therapy for such patients, it is usual practice that those presenting with signs and symptoms of heart failure, with raised NT-proBNP and evidence of LV systolic dysfunction to be treated with an ACEi/ARB and beta-blocker.
Our study adds to the growing literature of the impact of the COVID-19 pandemic on the care for patients with chronic heart failure [6]. Our data suggest that a transition towards telephone consultations and reduction in appointments with hospital heart failure nurses was associated with less successful optimisation of GDMT compared to usual care involving face-to-face clinics, with implications for service design during subsequent waves of the pandemic and beyond.
JJ and BN collected the data. SS and JJ analysed the data. MM and SS drafted the manuscript. JG and KKW provided critical revision. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.
Approval was given following institutional governance review following submission to the Clinical Audit Database at Leeds Teaching Hospital National Health Service Trust. The study was conducted in accordance with the principles outlined in the Declaration of Helsinki. In view of the retrospective nature, individual consent was waived as appropriate data protection safeguards were in place.
The authors would like to express their gratitude to all healthcare professionals at the Leeds Teaching Hospitals NHS Trust who cared for patients in this study in during the COVID-19 pandemic. The authors would also like to thank the reviewers for their valuable insights.
This research was funded by the British Heart Foundation, grant number FS/CRTF/20/24071.
KKW has received speakers’ fees and honoraria from Medtronic, Cardiac Dimensions, Novartis, Abbott, BMS, Pfizer, Bayer and has received an unconditional research grant from Medtronic. JG has received honoraria from Abbott, Medtronic and Microport and has received an unrestricted research grant from Medtronic. SS is funded by a British Heart Foundation Clinical Research Training Fellowship. None of the other authors have any disclosures.