The 2019 Yorkshire Turner-Warwick Lecture

The 2019 Yorkshire Turner-Warwick Lecture

Daniel Pan

NIHR Academic Clinical Fellow in Infectious Diseases and Medicine

Department of Respiratory Sciences, University of Leicester

Three important considerations for the general physician when

managing patients admitted to hospital with heart failure

Contents of talk

I have no conflicts of interest.

All views are my own.

Part 1: Three important considerations to take into account when

assessing the heart failure inpatient

Part 2: Prognostic value of the chest x-ray in the heart failure

inpatient

A case..

Isselbacher et al. Case 38 – 2018: A 54-Year-Old Man with New Heart Failure. New England

Journal of Medicine. 2018; 379:24 p2362-2372

Investigations

Haemoglobin: 14.6g/dL

WCC: 8.4 x103 per mm3

Platelets: 290 x103 per mm3

NT-pro BNP 8,352 pg/ml

Troponin: 71 ng/ml (non-dynamic)

Management

A diagnosis of heart failure, with volume overload is made.

Intravenous diuretics – Furosemide 40mg BD

Inpatient transthoracic echocardiogram

Heart failure nurse referral

Thomas et al. Calculation of left ventricular volumes and ejection fraction from biplane

Simpson’s formula using 2D echocardiography. J Nucl Med 2015;56:31S-38S

Over the course of the next week…

Oedema has improved.

Patient no longer symptomatic.

Passed mobility assessment by physiotherapy and occupational therapy

Furosemide switched to oral.

Prognostic medication – beta-blocker, ACE-inhibitor commenced and

uptitrated

Discharge – with heart failure follow-up in community

Before discharge…

‘Doctor, what is heart failure? Is it bad?’

-

Heart failure is increasing

British Heart Foundation

Heart failure is increasing

Conrad N et al. Temporal trends and patterns in heart failure incidence: a population-based study of 4 million

individuals. Lancet 2018;391:572–580.

A large proportion of patients admitted to hospital with heart

failure are looked after by general medicine

National cardiac audit programme. National Heart Failure Audit 2016-2017 summary report

Patients with heart failure have a high readmission rate within 30

days of discharge, before they can get seen by a heart failure

nurse

National cardiac audit programme. National Heart Failure Audit 2016-2017 summary report

Prognosis of patients with heart failure, especially those admitted

to hospital continues to be poor

Taylor et al. Trends in survival after a diagnosis of heart failure in the

United Kingdom 2000-2017: population based cohort

study BMJ 2019; 364 :l223

Grothey et al. Duration of adjuvant chemotherapy for stage II colon

cancer. New England Journal of Medicine 2018; 378;13 p 1177-1188.

Prognosis of heart failure is worse than some cancers

Mamas et al. Do patients have worse outcomes in heart failure than in cancer? A primary care‐based cohort study with 10‐year

follow‐up in Scotland. Eur J Heart Fail 2017, 19: 1095-1104.

What are patient’s perceptions of heart failure?

Plotka et al. Patients’ knowledge of heart failure and perception of the

disease. Patient Preference and Adherence 2017:11 1459-1467

Patients understanding, in their own words, of the term ‘heart failure’ at the time of the

survey (months after diagnosis was made).

P Banerjee et al. Clin Med 2010;10:339-343

0

10

20

30

40

50

60

Blood clot to

coronary

Damaged heart

muscle

Breathlessness No

understanding

No answer

Percentage

Percentage

Response to the questions ‘Did you understand the meaning of the term “heart

failure” at the time of diagnosis?’ and ‘Who gave you the diagnosis?’.

P Banerjee et al. Clin Med 2010;10:339-343

0

5

10

15

20

25

30

35

40

Yes No Do not

know

No

answer

General

practitioner

Hospital nurse

Hospital doctor

Other

Do not know

Did not answer

Point 1: Consider spending time to educate

patients about heart failure and its prognosis

What is heart failure?

Ponikowski et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart

failure. European Heart Journal 2016;37:2128-2200

Cowie et al. Improving care of patients with acute heart failure: before, during and after

hospitalization. ESC Heart Failure 2014:; 110-145.

‘Acute’ heart failure has many different causes

De Novo Acute

decompensation


hospitalization. ESC Heart Failure 2014:1; 110-145.

‘Acute’ heart failure may just be the natural history of

chronic heart failure

Rheumatic heart disease

Acute coronary syndrome

Post PCI/CABG

Age!

Multimorbidity

1970 2019

‘Acute’ heart failure 50 years ago is different to

‘acute’ heart failure today

The definition of heart failure itself is changing

Pre-1980s

‘Non-pharmacologic

era’

- Fluid restriction

- Bedrest

- Diuretics

1980s: Pharmacologic era

- Digitalis

- Diuretics

- Vasodilators

- Inotropes

1990s: Age of ACE

- ACEi

- Beta blockers

- Spironolactone

2000s: Decade of devices

- CRT, ICDs and

LVAD

Professor Andrew L Clark:

Heart failure with preserved ejection

fraction?

Or heart failure with normal ejection

fraction?

Now: Age of ARNIs

Return of the Diuretics?

Transplantation

Point 2: Don’t think acute heart failure – think

patients admitted to hospital with heart failure


hospitalization. ESC Heart Failure 2014:; 110-145.

‘Acute’ heart failure is not a single entity

Congestion

Residual congestion as an inpatient is related to worse prognosis

Rubio-Gracia et al. Prevalence, predictors and clinical outcome of residual congestion in acute

decompensated heart failure. International Journal of Cardiology 2018; 258. 185-191.

Congestion and relation to prognosis

Hasselblad et al. Relation between dose of loop diuretics and outcomes in a heart failure

population: Results of the ESCAPE Trial. European Journal of Heart Failure 2007, 9:1064-1069.

Pellicori et al. Prevalence, pattern and clinical relevance of ultrasound indices of congestion in

outpatients with heart failure. European Journal of Heart failure 2019, 21; 904-916

Congestion and relation to prognosis

McMurray et al. Dapaglifozin in patients with heart failure and reduced ejection fraction. The New

England Journal of Medicine September 2019

Is it simply just a diuretic effect?

Point 3: Although loop diuretics have not been

proven to relate to mortality, congestion is.

Treatment strategies

Identify the cause of the heart failure

Is this a traffic jam problem?

DISCLAIMER: my own view

Is this a mileage problem?

Heart failure ++ congestion = decongest

Heart failure + congestion = uptitrate

medications

The traffic jam problem

The heart is not working well, but the patient

is severely, acutely congested.

Heart failure ++ congestion = decongest

Heart failure + congestion = uptitrate

medications

The mileage problem

The patient is congested because the heart is

not working well.

Mullens et al. The use of diuretics in heart failure with congestion – a position statement from the Heart Failure

Association of the European Society of Cardiology. European Journal of Heart Failure 2019; 21(2): 137-155

Chest x-ray in acute heart failure

Battler. The Initial Chest X-ray in Acute Myocardial Infarction Prediction of Early and Late Mortality and

Survival. Circulation 1980:1004–10

Chest x-ray in acute heart failure

Core investigation in breathless patients.

Not considered a ‘diagnostic test’ for HF.

Little relation between cardiothoracic ratio and left ventricular systolic

function. (1)

Not all patients with acute HF have pulmonary congestion. (2)

Only studies investigating prognosis are those 20-40 years ago, when

most patients with pulmonary congestion had acute myocardial

infarction. (3-7)

(1) Clark et al.. Unreliability of cardiothoracic ratio as a marker of left ventricular impairment: Comparison with radionuclide ventriculography and echocardiography. Postgrad Med J 2000;76:289–91

(2) Allen et al. Improving Time to Diagnosis How to Improve Time to Diagnosis in Acute Heart Failure – Clinical Signs and Chest X-ray Improving Time to Diagnosis. 2015;:69–74

(3) Petrie et al. It cannot be cardiac failure because the heart is not enlarged on the chest x-ray. Eur J Heart Fail 2003;5:117–9

(4) Roguin et al.. Long-term prognosis of acute pulmonary oedema--an ominous outcome. Eur J Hear Fail J Work Gr Hear Fail Eur Soc Cardiol 2000;2:137–44

(5) Battler et al. The Initial Chest X-ray in Acute Myocardial Infarction Prediction of Early and Late Mortality and Survival. Circulation 1980:1004–10

(6) Brezins et al. Left ventricular function in patients with acute myocardial infarction, acute pulmonary edema, and mechanical ventilation: Relationship to prognosis. Crit Care Med 1993;21:380–5

(7) Lin et al.. Reappraisal of continuous positive airway pressure therapy in acute cardiogenic pulmonary edema: Short-term results and long-term follow-up. Chest 1995;107:1379–86

Study aim

To investigate the prevalence and

prognostic significance of signs of heart

failure on the chest radiograph, in patients

admitted to hospital with acute heart failure

OPERA-HF

Observational study to PrEdict ReAdmission for Heart Failure patients

Prospective observational study (October 2012-November 2016)

Inclusion criteria:

- Age >18 years of age

- Usual residence in the region

- Hospitalisation with heart failure

- Treatment with loop diuretics

And one of the follow:

-Left ventricular ejection fraction ≤40%

-Left atrial dimension≥4.0cm

-N-terminal pro-B-type natriuretic peptide (NT-proBNP)>400 pg/mL (if in sinus rhythm) or

>1200 pg/mL (if in atrial fibrillation – AF) ISRCTN96643197

Kerley B lines

• Short horizontal lines

situated perpendicularly to

the pleural surface and

between the lung lobes in

the interstitium

Alveolar oedema

• Fluffy shadowing in the

lung fields. Severe is

defined as present

throughout all lung fields.

Pleural effusion

• Costophrenic and

cardiophrenic angle

blunting

Cardiothoracic ratio = A+B/2C

Chest x-ray projection

• Posterior-anterior

• Anterior-posterior

C B

A

Pulmonary venous congestion

• Increase in proportion of

vessels in the upper lung zones

compared to lower lung zones

Danzer CS. The cardio-thoracic ratio: An index of cardiac enlargement. Am J Med Sci 1919; 157:513-52

Illustration: Pan et al. 2019 Unpublished.

Enrolled in OPERA-HF: 1145 patients

No CXR during admission: 70 patients

Remaining: 1075 patients

CXR grossly rotated: 59 patients

No erect CXR: 41 patients

Remaining: 975 patients

Pan et al 2019. Unpublished

Clinical variables

Age

Gender

Hospitalised for HF

in previous year

Prior MI

Prior CABG

Malignancy

Diabetes

COPD

ACS on admission

SBP/DBP

Degree of

breathlessness

Investigation variables

Presence/absence of LVSD

AF

QRS duration

Heart rate

Cardiothoracic ratio

Film projection (AP/PA)

Alveolar oedema

Kerley B lines

Pleural effusion


Laboratory variables

Sodium

Potassium

Urea

Troponin T

NT-proBNP

Hb

Chloride

Albumin

Outcomes

In-hospital mortality

30 day mortality

Readmission to

hospital within 30

days of discharge

All-cause mortality

at end of followup

x975

Research is not a piece of cake…

Most patients with AHF did not present with ACS

Median age: 77 (68-83)

Median NT-proBNP: 5047 pg/ml (2337-10945) (26% did not have one taken

on admission)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Male Hospitalised for

heart failure in the

previous year

Presented with

acute coronary

syndrome

Breathlessness at

rest

Atrial fibrillation Reduced left

ventricular

ejection fraction

Study demographics

Yes NoPan et al 2019. Unpublished

The traffic jam

Mileage

Don’t think acute heart failure – think patients

admitted to hospital with heart failure

Pulmonary congestion is common in AHF

Median cardiothoracic ratio: PA films: 0.57 (0.55-0.64);

AP films: 0.60 (0.55-0.64)

Cardiomegaly present in 67%; unmeasurable in 6%.

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Film projection (A -

AP, B - PA)

Alveolar oedema (A -

present, B - absent)

Kerley B lines (A -


Pleural effusions (A-


Pulmonary venous

congestion - (A -


Chest x-ray findings (N=975)

A B

33%

No congestive features 5%

Pulmonary venous

congestion

Kerley B lines

Pleural effusions 4%

4%

2%

3%

1%

1%

3%

2%

3%

9%

7%

8%

5% 10%

Alveolar oedema

Features of pulmonary congestion occur together

Sensitivity = probability

of a positive test given the

patient has a disease

= 95%

Pulmonary congestion gets worse in AP films,

with larger cardiothoracic ratios

Follow-up results

Median followup – 671 days (1.8 years)

440 (45% patients died)

41 during index admission

19% of patients were readmitted with worsening HF within

30 days of discharge from index admission.

Chest x-ray findings had no relation to short term outcomes

Consider spending time to educate patients

about heart failure and its prognosis

Although loop diuretics have not been proven to

relate to mortality, congestion is.

Creation of a chest x-ray prognostic score

Assessment of whether the score is related to prognosis when considered in a multivariable analysis

Assessment of whether the score is additionally useful in assessment of prognosis in addition to other variables

Statistical analysis strategy

Outcome: all-cause

mortality

Hazard ratio

(95% CI)

Wald X2 P value Hazard ratio (95%

CI)

β-coefficient Score

Alveolar oedema

Absent Referent Referent Referent Referent Referent 0

Present 1.20 (0.98-1.47) 1.71 0.09 1.04 (0.84-1.31) 0.05 1

Severe 1.67 (1.22-2.28) 3.20 0.001 1.35 (0.97-1.88) 0.30 3

Kerley B lines


Present 1.28 (1.04-1.59) 2.30 0.02 1.21 (0.98-1.51) 0.19 2

Cardiothoracic ratio

≤0.55 Referent Referent Referent Referent Referent 0

0.55-0.70 1.21 (0.96-1.52) 1.62 0.10 1.12 (0.89-1.41) 0.12 1

>0.70/unmeasurable 1.84 (1.35-2.50) 3.84 <0.001 1.60 (1.16-2.19) 0.46 5

Chest x-ray projection

Posterior-anterior Referent Referent Referent Referent Referent 0

Anterior-posterior 1.13 (1.07-1.20) 4.28 <0.001 1.47 (1.17-1.86) 0.38 4

Pleural effusions


Present 1.29 (1.05-1.59) 2.47 0.01 1.12 (0.89-1.40) 0.11 1


Absent Referent Referent Referent N/A N/A N/A

Present 1.06 (0.85-1.33) 0.53 0.60 N/A N/A N/A

Chest x-ray score

Chest x-ray score 1.10 (1.07-1.13) 6.15 <0.001 N/A N/A N/A

Austin PC et al. Developing points-based risk-scoring systems in the presence of competing risks. Stat Med 2016;35:4056–72

Pan et al. 2019 Unpublished

Creating the chest x-ray score

Relation of chest x-ray score to patient demographics

Older age

Female

Prior CABG

Worsening

breathlessness Increasing potassium

Increasing urea

Increasing creatinine

Increasing NT-proBNP

Decreasing albumin

Decreasing haemoglobin

Increasing chest x-ray score

(univariable analysis)

Decreasing diastolic BP

Relation to death (Univariable Cox analysis)

Older age

Lower diastolic BP

Prior CABG

Increasing potassium Increasing urea

Increasing creatinine

Increasing NT-proBNP

Decreasing albumin

Decreasing

haemoglobin

Female

Worsening

breathlessness

Chest x-ray score is related to death on multivariable

Cox regression

0.5 1 1.5

Age (per year increase)

Systolic blood pressure – mmHg (per 10 unit increase

Heart rate – beats/minute (per 10 unit increase)

Sodium – mmol/L– beats/minute (per 10 unit increase)

Urea – mmol/L– beats/minute (per 10 unit increase)

Chloride – mmol/L– beats/minute (per 10 unit increase)

Albumin– mmol/L– beats/minute (per 10 unit increase)

Chest x-ray score – mmol/L (per 10 unit increase

Hazard ratio

Base model

….but it does not offer any additional prognostic

value compared to other routinely collected variables

Return of the chest x-ray - main findings

Radiological evidence of congestion is very common in patients

presenting to hospital with heart failure.

Patients presenting with breathlessness as their dominant

symptom, have a higher chest x-ray score

Increasing pulmonary congestion on the chest x-ray score is

related to worsening heart failure as assessed by other clinical

measures and all-cause mortality.

Applications

Everyone gets a chest x-ray. This could used a systematic way of

grading chest x-rays in clinical trails

Evaluation of different phenotypes of pulmonary congestion and

association with prognosis

Anterior-posterior films. Why are they related to a worse

prognosis?

Limitations

Single – centre study

Most patients – Caucasian ethnicity

Previous congestion scores exist, but are more research

orientated, clunky to use.

Needs validation

No radiologists..

Considerations for the general physician

Educating patients about heart failure prognosis

is every general physician’s responsibility

Don’t think acute heart failure – think patients

admitted to hospital with heart failure

Although loop diuretics have not been shown to

relate to prognosis, congestion is.

Back to our patient

Regional wall motion abnormalities on the echo.

Normal other results – diagnosis of HF-rEF was

made, secondary to ischaemic heart disease.

Patient was also commenced on antiplatelet

therapy.

The diagnosis and prognosis of heart failure was

explained. Strict uptitration of heart failure

medications emphasized.

“The way to lead a long life is to get a chronic disease and take

care of it.”

Sir William Osler

Thank you! Contact: [email protected]

Academic Cardiology team at Castle Hill

Hospital

Supervision

Professor Andrew Clark – taught me how to

really calculate the cardiothoracic ratio

Dr Pierpaolo Pellicori

Data collection

Dr Alessia Urbinati

Dr Ioanna Sokoreli

Dr Shirley Sze

Dr Oliver Brown

Statistics advice

Professor Alan Rigby

Research database management

Syed Kazmi

General advice:

Dr Jarno Riistama

Professor John Cleland

Heart failure nurses

Karen Dobbs

Jeanne Bulemfu

Documents

The 2019 Yorkshire Turner-Warwick Lecture