Symptoms as a Predictor of the Placebo-Controlled Efficacy of PCI in Stable Coronary Artery Disease.

BACKGROUND: Placebo-controlled evidence from ORBITA-2 found that percutaneous cutaneous intervention (PCI) in stable coronary artery disease with little or no antianginal medication relieved angina, but residual symptoms persisted in many. The reason for this was unclear. OBJECTIVES: ; This ORBITA-2 secondary analysis investigates the relationship between presenting symptoms and disease severity (anatomic, non-invasive, and invasive ischemia) and the ability of symptoms to predict the placebo-controlled efficacy of PCI. METHODS: Pre-randomization symptom severity and nature were assessed using the ORBITA smartphone application and symptom and quality of life questionnaires including the Rose angina questionnaire. Disease severity was assessed using quantitative coronary angiography (QCA), stress echocardiography, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR). Bayesian ordinal regression was used. RESULTS: At pre-randomization, the median number of daily angina episodes was 0.8 (0.4-1.6), 64% had Rose angina, QCA diameter stenosis 61 (49-74), stress echocardiography score 1.0 (0.0-2.7), FFR 0.63 (0.49-0.75), and iFR 0.78 (0.55-0.87). There was little relationship between symptom severity and nature and disease severity: angina symptom score with QCA ordinal correlation coefficient 0.06 (95% CrI 0.00 to 0.08); stress echocardiography 0.09 (95% CrI 0.02 to 0.10); FFR 0.04 (95% CrI -0.03 to 0.07); and iFR 0.04 (95% CrI -0.01 to 0.07). However, Rose angina and guideline-based typical angina were strong predictors of placebo-controlled PCI efficacy (angina symptom score: OR 1.9, 95% CrI 1.6 to 2.1, Pr(Interaction)=99.9% and OR 1.8, 95% CrI 1.6 to 2.1, Pr(Interaction)=99.9%, respectively). CONCLUSIONS: Although symptom severity and nature were poorly associated with disease severity, the nature of symptoms powerfully predicted the placebo-controlled efficacy of PCI.

N-of-1 Trial of Angina Verification Before Percutaneous Coronary Intervention.

BACKGROUND: In stable coronary artery disease, 30% to 60% of patients remain symptomatic despite successful revascularization. Perhaps not all symptoms reported by a patient with myocardial ischemia are, in fact, angina. OBJECTIVES: This study sought to determine whether independent symptom verification using a placebo-controlled ischemic stimulus could distinguish which patients achieve greatest symptom relief from percutaneous coronary intervention (PCI). METHODS: ORBITA-STAR was a multicenter, n-of-1, placebo-controlled study in patients undergoing single-vessel PCI for stable symptoms. Participants underwent 4 episodes (60 seconds each) of low-pressure balloon occlusion across their coronary stenosis, randomly paired with 4 episodes of placebo inflation. Following each episode, patients reported the similarity of the induced symptom in comparison with their usual symptom. The similarity score ranged from -10 (placebo replicated the symptom more than balloon occlusion) to +10 (balloon occlusion exactly replicated the symptom). The primary endpoint was the ability of the similarity score to predict symptom relief with PCI. RESULTS: Fifty-one patients were recruited, aged 62.9 ± 8.6 years. The median fractional flow reserve was 0.68 (Q1-Q3: 0.57-0.79), and the instantaneous wave-free ratio was 0.80 (Q1-Q3: 0.48-0.89). The median similarity score was 3 (Q1-Q3: 0.875-5.25). The similarity score was a strong predictor of symptom improvement following PCI: a patient with an upper quartile similarity score of 5.25 was significantly more likely to have lower angina frequency at follow-up (OR: 8.01; 95% credible interval: 2.39-15.86) than a patient with a lower quartile similarity score of 0.875 (OR: 1.31; 95% credible interval: 0.71-1.99), Pr(difference) >99.9%. CONCLUSIONS: Similarity score powerfully predicted symptom improvement from PCI. These data lay the foundation for independent symptom mapping to target PCI to those patients most likely to benefit. (Systematic Trial of Angina Assessment Before Revascularization [ORBITA-STAR]; NCT04280575).

Coronary sinus reducer for the treatment of refractory angina (ORBITA-COSMIC): a randomised, placebo-controlled trial.

BACKGROUND: The coronary sinus reducer (CSR) is proposed to reduce angina in patients with stable coronary artery disease by improving myocardial perfusion. We aimed to measure its efficacy, compared with placebo, on myocardial ischaemia reduction and symptom improvement. METHODS: ORBITA-COSMIC was a double-blind, randomised, placebo-controlled trial conducted at six UK hospitals. Patients aged 18 years or older with angina, stable coronary artery disease, ischaemia, and no further options for treatment were eligible. All patients completed a quantitative adenosine-stress perfusion cardiac magnetic resonance scan, symptom and quality-of-life questionnaires, and a treadmill exercise test before entering a 2-week symptom assessment phase, in which patients reported their angina symptoms using a smartphone application (ORBITA-app). Patients were randomly assigned (1:1) to receive either CSR or placebo. Both participants and investigators were masked to study assignment. After the CSR implantation or placebo procedure, patients entered a 6-month blinded follow-up phase in which they reported their daily symptoms in the ORBITA-app. At 6 months, all assessments were repeated. The primary outcome was myocardial blood flow in segments designated ischaemic at enrolment during the adenosine-stress perfusion cardiac magnetic resonance scan. The primary symptom outcome was the number of daily angina episodes. Analysis was done by intention-to-treat and followed Bayesian methodology. The study is registered with ClinicalTrials.gov, NCT04892537, and completed. FINDINGS: Between May 26, 2021, and June 28, 2023, 61 patients were enrolled, of whom 51 (44 [86%] male; seven [14%] female) were randomly assigned to either the CSR group (n=25) or the placebo group (n=26). Of these, 50 patients were included in the intention-to-treat analysis (24 in the CSR group and 26 in the placebo group). 454 (57%) of 800 imaged cardiac segments were ischaemic at enrolment, with a median stress myocardial blood flow of 1·08 mL/min per g (IQR 0·77-1·41). Myocardial blood flow in ischaemic segments did not improve with CSR compared with placebo (difference 0·06 mL/min per g [95% CrI -0·09 to 0·20]; Pr(Benefit)=78·8%). The number of daily angina episodes was reduced with CSR compared with placebo (OR 1·40 [95% CrI 1·08 to 1·83]; Pr(Benefit)=99·4%). There were two CSR embolisation events in the CSR group, and no acute coronary syndrome events or deaths in either group. INTERPRETATION: ORBITA-COSMIC found no evidence that the CSR improved transmural myocardial perfusion, but the CSR did improve angina compared with placebo. These findings provide evidence for the use of CSR as a further antianginal option for patients with stable coronary artery disease. FUNDING: Medical Research Council, Imperial College Healthcare Charity, National Institute for Health and Care Research Imperial Biomedical Research Centre, St Mary's Coronary Flow Trust, British Heart Foundation.

The effect of ethnicity and socioeconomic status on outcomes after resuscitated out-of-hospital cardiac arrest - Findings from a tertiary centre in South London.

Background: Out-of-hospital cardiac arrest is a common cause of morbidity and mortality, and ethnic variation in outcomes is recognised. We investigated ethnic and socioeconomic differences in arrest circumstances, rates of coronary artery disease, treatment, and outcomes in resuscitated OOHCA. Methods: Patients with resuscitated OOHCA of suspected cardiac aetiology were included in the King's Out-of-Hospital Cardiac Arrest Registry between 1-May-2012 and 31-December-2020. Results: Of 526 patients (median age 62.0 years, IQR 21.1, 74.1% male), 414 patients (78.7%) were White, 35 (6.7%) were Asian, and 77 (14.6%) were Black. Black patients had more co-existent hypertension (p = 0.007) and cardiomyopathy (p = 0.003), but less prior coronary revascularisation (p = 0.026) compared with White/Asian patients. There were no ethnic differences in location, witnesses, or bystander CPR, but Black patients had more non-shockable rhythms (p < 0.001). Black patients received less immediate coronary angiography (p < 0.001) and percutaneous coronary intervention (p < 0.001) but had lower rates of CAD (p = 0.004) than White/Asian patients. All-cause mortality at 12 months was highest amongst Black patients, followed by Asian and then White patients (57.1% vs 48.6% vs 41.3%, p = 0.032). In Black patients, excess mortality was driven by higher rates of multi-organ dysfunction but lower cardiac death than White/Asian patients, with cardiac death highest amongst Asian patients (p = 0.009). Socioeconomic status had no effect on mortality, and in a multivariable logistic regression, age, location, witnesses, and Black compared to White ethnicity were independent predictors of mortality, whilst social deprivation was not. Conclusion: In this single-centre study, Black patients had higher mortality after resuscitated OOHCA than White/Asian patients. This may be in part due to differing underlying aetiology rather than differences in arrest circumstances or social deprivation.

Spinal cord infarction post cardiac arrest in STEMI: A potential complication of intra-aortic balloon pump use.

Intra-aortic balloon pump (IABP) is commonly used as a cardiac assist device in various clinical situations: cardiogenic shock, mechanical complications of acute myocardial infarction, high risk percutaneous coronary interventions, coronary artery bypass graft surgery and refractory unstable angina and ventricular arrhythmias as bridge to therapy. Although current data support its safety, there is limited or no support for its efficacy. We present the case of spinal cord infarction after IABP use in a patient who presented with ST elevation myocardial infarction and cardiac arrest and we discuss the potential mechanism of such a devastating complication.

Recanalized chronic coronary thrombus: unraveling a hazy coronary lesion by intravascular ultrasound.

Hazy lesions in coronary angiography can often be a puzzle for the interventional cardiologist. Recanalized chronic coronary thrombus, although rare, is one of the potential diagnoses. Intracoronary imaging with intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are tools that can guide to the correct diagnosis. We present the images of a case where IVUS was used to unravel such a lesion.