Background

Traditional Stress Echo

• Identification of regional wall motion abnormalities to identify obstructive coronary artery disease
  • Qualitatively assessed

• Other prognostic parameters:
  • Exercise duration, BP response, ST-T changes and LV dilation (not reliably reported)

• Functional test: thus does not diagnose non-obstructive atherosclerotic disease that can still cause events

Compared to Alternatives

• Advantages
  • ​Inexpensive
  • No radiation
  • Portable
  • Exercise and non-exercise
  • Less environmental impact compared to MRI/SPECT

Marwick 2021

Compared to Alternatives

• Disadvantages
  • Functional testing thus may not pick up non-obstructive clinical atherosclerosis that can cause future events
    • Compared to Coronary CT
  • WMA are later in the ischemic cascade (not capturing perfusion changes)
    • Compared to myocardial perfusion imaging
  • WMA based protocol less useful in evaluating INOCA (ischemia with no obstructive CAD)

Pelikka 2019

Pelikka 2019

Pelikka 2019

Rest

Post Exercise

LAD Ischemia

Why New Protocol?

• Change in referral pattern leading to a dropping positivity rate (<10% in some studies)
  • Reduced predictive value

• Traditional stress echo protocol does not capture other areas of vulnerability in a heterogeneous population beyond identifying obstructive CAD
  • ie. lung water, LV contractile reserve, coronary microcirculation and cardiac autonomic dysfunction

• New parameters are able to be implemented in Echo Labs without new technologies/sofware

ABCDE-SE Protocol

ABCDE-SE Protocol

A - Wall motion abnormalities, volumes*

B - B Lines

C - Left ventricular contractile reserve*

D - Coronary flow reserve

E - Heart rate reserve*

*do not require additional imaging based on current protocol

ABCDE Stress Echo

Step A: Myocardial Ischemia

• Assessment: Wall motion score index, 1 (normal) - 4 (dyskinetic) in a 17 segment LV model
• Positivity: 2 adjacent segments of same vascular territory increment by at least 1 point

GrepMed

Picano 2017

Step B: B Lines

• Assessment: 4 quadrant lung ultrasound for b lines
• Positivity: 2 or more  

Scali 2020

• Used in subsequent Stress Echo 2020/2030 studies
• Cardiac transducer
• Perpendicular to ribs
• 18cm depth
• 6s clips

Step B: B Lines

Scali MC, et al. (2020) Lung Ultrasound and Pulmonary Congestion During Stress Echocardiography. JACC Cardiovasc Imaging 13:2085-95.

Arntfield 2021

Step C: LVCR

• Assessment: Left ventricular contractile reserve is calculated as systolic blood pressure/end-systolic volume
• Positivity: LVCR < 2 for exercise/dobutamine or <1 for vasodilators

Picano 2020

Step C: LVCR

• Lower number is worse (<2 for exercise or dobutamine)
• Combines two prognostic variables
  • SBP not rising (or decreasing)
  • ESV increasing
• Creates a unitless variable that is not load dependent

Picano 2020

Step D: CFVR

• Assessment: Coronary flow velocity reserve of mid-distal LAD

• Positivity: CFVR < 2 

• Success rate of 88% in obtaining CFVR on LAD (3000/3410)
  • 80% with exercise (bike) and 81% with dobutamine
  •  Acquisition and Interpretation in < 4 minutes

• Assesses both epicardial CAD and coronary microcirculation

• Dopplers obtained and reviewed offline

Ciampi 2019

Step D: CFVR

• Acquisition: modified low parasternal and apical views
• Studies agree, onerous, but with training it is possible

Krzanowski 2003

Step D: CFVR

• Acquisition: modified low parasternal and apical views
• Studies agree, onerous, but with training it is possible

Mod PSAX

Mod PLAX

Krzanowski 2003

Step D: CFVR

Cardiology 4U

Step D: CFVR

Cardiology 4U

Ciampi 2019

Ciampi 2019

• Angina
• No WMA
• CFVR < 2
• Dx:  chronic microvascular dysfunction

Kardos 2023

Gulati 2021

Example: Normal

Example: Abnormal

Study

European Heart Journal 2021

Ciampi et al.

Prognostic value of stress echocardiography assessed by the ABCDE protocol

Design

• Design: prospective, multi-centre, international, effectiveness study
• Intervention: ABCDE stress echo protocol
• Patients: known or suspected chronic coronary syndrome
• Outcomes: All cause death

Inclusion/Exclusion

• age >18 years
• referral for known or suspected CAD
• no severe primary valvular or congenital heart disease, or presence of prognosis-limiting comorbidities, such as advanced cancer, reducing life expectancy to <1 year
• echocardiography of acceptable quality at rest and during stress

Results

• Of those with normal SE who underwent coronary angiography, 30% demonstrated obstructive CAD, whereas in those with all five abnormal steps on SE, 95% had significant CAD.

Predictors of Mortality

• Postive:
  • B-lines
  • Coronary flow velocity reserve
  • Heart rate reserve
  • ABCDE Score 3 or greater
• Negative:
  • Regional Wall Motion Abnormalities
  • Left ventricular contractile reserve

• The mortality rate was 0.4%/year for a normal SE compared with 2.7%/year when all SE steps were abnormal.

Incremental Benefit

Study Conclusions

• Higher ABCDE score predicts less benign outcome

• Regional wall motion abnormalities, most used measure, less helpful in predicting prognosis

• Steps B-E are feasibly added to current stress echo protocols

• Shift assessing only coronary stenosis to patient as a whole
  • Other vulnerabilities including coronary microvascular dysfunction and autonomic dysfunction

Study Conclusions

• Consider targeting treatments towards the identified abnormal steps

• Stress echo low cost/risk/environmental impact and no radiation

• ABCDE protocol can be used with any stress - exercise or pharmacological (ie. in a global pandemic pharm preferred)

Proposed Tailored Therapy

• Step A identifies inducible ischemia --> BB/CCB/nitrates or possible revasc

• Step B identifies pulmonary congestion --> diuretics

• Step C (LVCR) identifies LV dysfunction --> ACEi

• Isolated Step D identifies microvascular dx --> statin

• Step E abnormalities can be targets by neurohormonal modulation (ie. BB/ACEi/MRA/renal denervation)

Treatments potentially titratable to ABCDE risk score

Discussion

Discussion

• Dedicated training required to implement protocol
  • Specifically coronary flow of LAD is most challenging

• Originally planned 5000 patients and 3 year followup but achieved ~3600 and 21 month followup
  • 2020 was planned last year of study but COVID

• No other end points other than mortality to assess predictive power of protocol steps
  • Ie. B-lines and HF admissions

Discussion

• Images were not reviewed by core lab
  • Practical for effectiveness study as has real-world applicability

• Parameters were binary, positive or negative, future studies plan to consider mild-mod-severe stratification

• Most patients underwent dipyridamole stress, would be beneficial to compare predictive value of the steps by stress modality (could explain why physiological measures such as LVCR were not predictive)
  • High score 4-5 were mostly in exercise group

Discussion

• RWMA may not be a strong enough tool to assess for ischemia as significant oxygen supply demand mismatch is needed
  • Future protocols could employ myocardial contrast echocardiography to assess perfusion
  • Low usage of contrast in general in the study

• Functional testing may not pick up non-obstructive lesions which can still lead to to events
  • Critics recommend carotid ultrasound to pick up on clinical atherosclerosis

Where now?

Modified ABCDE?

ABCDE+

ABCDE + F (regurgitant flow) G (LVOT gradients) L (left atrial volume/function) P ( pulmonary and LV pressures) L (RV function)

Stress Echo 2030

ABCDE + F (regurgitant flow) G (LVOT gradients) L (left atrial volume/function) P ( pulmonary and LV pressures) L (RV function)

Stress Echo 2030

• 1-SE in coronary artery disease (SECAD)
• 2-SE in diastolic heart failure (SEDIA)
• 3-SE in hypertrophic cardiomyopathy (SEHCA)
• 4-SE post-chest radiotherapy and chemotherapy (SERA)
• 5-Artificial intelligence SE evaluation (AI-SEE)
• 6-Environmental stress echocardiography and air pollution (ESTER)
• 7-SE in repaired Tetralogy of Fallot (SETOF)
• 8-SE in post-COVID-19 (SECOV)
• 9: Recovery by stress echo of conventionally unfit donor good hearts (RESURGE)
• 10-SE for mitral ischemic regurgitation (SEMIR)
• 11-SE in valvular heart disease (SEVA)
• 12-SE for coronary vasospasm (SESPASM)