Ethnicity Differences in Geometric Remodeling and Myocardial Composition in Hypertension unveiled by Cardiovascular Magnetic Resonance.

AIMS: Hypertensive patients of African-ancestry (Afr-a) have higher incidences of heart failure and worse clinical outcomes than hypertensive patients of European-ancestry (Eu-a), yet the underlying mechanisms remain misunderstood. This study investigated right (RV) and left (LV) ventricular remodeling alongside myocardial tissue derangements between Afr-a and Eu-a hypertensives. METHODS AND RESULTS: Sixty-three Afr-a and forty-seven Eu-a hypertensives underwent multi-parametric cardiovascular-magnetic-resonance. Biventricular volumes, mass, function, mass/end-diastolic volume (M/V) ratios, T2- and pre/post-contrast T1-relaxation-times, synthetic-extracellular-volume (s-ECV) and myocardial fibrosis (MF) were measured. Three-dimensional shape modeling was implemented to delineate ventricular geometry.LV and RV-mass (indexed to body-surface-area) and M/V ratios were significantly greater in Afr-a than Eu-a hypertensives (67.1±21.7 vs. 58.3±16.7g/m2, 12.6±3.48 vs. 10.7±2.71g/m2, 0.79±0.21 vs. 0.70±0.14g/ml, 0.16±0.04 vs. 0.13±0.03g/ml, respectively; P<0.03) mirroring LV remodeling. Afr-a patients showed greater basal-interventricular-septum thickness than Eu-a patients, which may influence LV hypertrophy and RV cavity changes. This biventricular remodeling was associated with prolonged T2-relaxation-time (47.0±2.2 vs. 45.7±2.2ms, P=0.005) and higher prevalence (23% vs. 4%, P=0.001) and extent of MF (2.3[0.6-14.3] vs. 1.6[0.9-2.5] % of LV-mass, P=0.008) in Afr-a patients. Multivariable linear regression showed modifiable cardiovascular risk-factors and greater end-diastolic volume were independently associated with greater LV or RV-mass. Furthermore, ethnicity was independently associated with greater RV-mass, supporting our hypothesis of ethnic-specific hypertensive remodeling. CONCLUSIONS: Afr-a hypertensives had distinctive biventricular remodeling, including increased RV-mass and septal thickening, and subtle myocardial tissue abnormalities compared to Eu-a hypertensives. From this study, modifiable cardiovascular risk-factors, and ventricular geometry, but not ethnicity, were independently associated with higher LV mass.

Global Longitudinal Strain as Predictor of Inducible Ischemia in No Obstructive Coronary Artery Disease in the CIAO-ISCHEMIA Study.

BACKGROUND: Global longitudinal strain (GLS) is a sensitive marker for identifying subclinical myocardial dysfunction in obstructive coronary artery disease (CAD). Little is known about the relationship between GLS and ischemia in patients with myocardial ischemia and no obstructive CAD (INOCA). OBJECTIVES: To investigate the relationship between resting GLS and ischemia on stress echocardiography (SE) in patients with INOCA. METHODS: Left ventricular GLS was calculated offline on resting SE images at enrollment (n = 144) and 1-year follow-up (n = 120) in the CIAO-ISCHEMIA (Changes in Ischemia and Angina over One year in International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial screen failures with no obstructive CAD on computed tomography [CT] angiography) study, which enrolled participants with moderate or severe ischemia by local SE interpretation (≥3 segments with new or worsening wall motion abnormality and no obstructive (<50% stenosis) on coronary computed tomography angiography. RESULTS: Global longitudinal strain values were normal in 83.3% at enrollment and 94.2% at follow-up. Global longitudinal strain values were not associated with a positive SE at enrollment (GLS = -21.5% positive SE vs GLS = -19.9% negative SE, P = .443) or follow-up (GLS = -23.2% positive SE vs GLS = -23.1% negative SE, P = .859). Significant change in GLS was not associated with positive SE in follow-up (P = .401). Regional strain was not associated with colocalizing ischemia at enrollment or follow-up. Changes in GLS and number of ischemic segments from enrollment to follow-up showed a modest but not clinically meaningful correlation (ß = 0.41; 95% CI, 0.16, 0.67; P = .002). CONCLUSIONS: In this cohort of INOCA patients, resting GLS values were largely normal and did not associate with the presence, severity, or location of stress-induced ischemia. These findings may suggest the absence of subclinical myocardial dysfunction detectable by echocardiographic strain analysis at rest in INOCA.

Outcomes With Intermediate Left Main Disease: Analysis From the ISCHEMIA Trial.

BACKGROUND: Patients with significant (≥50%) left main disease (LMD) have a high risk of cardiovascular events, and guidelines recommend revascularization to improve survival. However, the impact of intermediate LMD (stenosis, 25%-49%) on outcomes is unclear. METHODS: Randomized ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) participants who underwent coronary computed tomography angiography at baseline were categorized into those with (25%-49%) and without (<25%) intermediate LMD. The primary outcome was a composite of cardiovascular mortality, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. The primary quality of life outcome was the Seattle Angina Questionnaire summary score. RESULTS: Among the 3699 participants who satisfied the inclusion criteria, 962 (26%) had intermediate LMD. Among invasive strategy participants with intermediate LMD on coronary computed tomography angiography, 49 (7.0%) had significant (≥50% stenosis) left main stenosis on invasive angiography. Patients with intermediate LMD had a higher risk of cardiovascular events in the unadjusted but not in the fully adjusted model compared with those without intermediate LMD. An invasive strategy increased procedural MI and decreased nonprocedural MI with no significant difference for other outcomes including the primary end point. There was no meaningful heterogeneity of treatment effect based on intermediate LMD status except for nonprocedural MI for which there was a greater absolute reduction with invasive management in the intermediate LMD group (-6.4% versus -2.0%; Pinteraction=0.049). The invasive strategy improved angina-related quality of life and the benefit was durable throughout follow-up without significant heterogeneity based on intermediate LMD status. CONCLUSIONS: In the ISCHEMIA trial, there was no meaningful heterogeneity of treatment benefit from an invasive strategy regardless of intermediate LMD status except for a greater absolute risk reduction in nonprocedural MI with invasive management in those with intermediate LMD. An invasive strategy increased procedural MI, reduced nonprocedural MI, and improved angina-related quality of life. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01471522.

Natural History of Patients With Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study.

BACKGROUND: Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. METHODS: CIAO-ISCHEMIA (Changes in Ischemia and Angina over One Year in ISCHEMIA Trial Screen Failures With INOCA) was an international cohort study conducted from 2014 to 2019 involving angina assessments (Seattle Angina Questionnaire) and stress echocardiograms 1 year apart. This was an ancillary study that included patients with a history of angina who were not randomly assigned in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease status, and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between the changes in the Seattle Angina Questionnaire angina frequency score and changes in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and we compared CIAO participants with ISCHEMIA participants with obstructive coronary artery disease who had stress echocardiography before enrollment, as CIAO participants did. RESULTS: INOCA participants in CIAO were more often female (66% of 208 versus 26% of 865 ISCHEMIA participants with obstructive coronary artery disease, P<0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [interquartile range, 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (P=0.46) or ISCHEMIA stress echocardiography participants (P=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants, and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over 1 year was not significantly correlated with change in angina (ρ=0.029). CONCLUSIONS: Improvement in ischemia and angina were common in INOCA but not correlated. Our INOCA cohort had a degree of inducible wall motion abnormalities similar to concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02347215.

NHS England-funded CT fractional flow reserve in the era of the ISCHEMIA trial.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) 2016 guidelines (CG95) recommend patients with new stable chest pain be investigated with computed tomography coronary angiography (CTCA). An updated guideline (MTG32) recommended using CT fractional flow reserve (CTFFR) as a gatekeeper to invasive coronary angiography (ICA) for patients with coronary stenosis on CTCA. Subsequently, NHS England negotiated a UK-wide contract with HeartFlow, the provider of CTFFR. We describe our experience with CTFFR and consider the impact of the recent ISCHEMIA trial on these guidelines. METHODS: We prospectively collected ICA and revascularisation data on all patients undergoing CTFFR from January 2019 to March 2020. RESULTS: One-hundred and twenty-five of 140 patients completed CTFFR analysis. Eighty-one patients had CTCA stenosis >50%. Thirty-six had positive CTFFR; 29 underwent ICA with 22 (75.9%) revascularised. Forty-five had negative CTFFR; 14 underwent ICA and four (28.6%) were revascularised. The average cost of investigation per patient (PP) was £971.95. Had these patients undergone ICA directly with no functional test after CTCA, the average cost would be £932.51 PP. CONCLUSION: Our revascularisation rates suggest that CTFFR can potentially be a gatekeeper to ICA but does not necessarily yield cost savings.

Computed tomography coronary angiography: Diagnostic yield and downstream testing.

BACKGROUND: The UK National Institute for Health and Care Excellence (NICE) updated its guidelines on stable chest pain in 2016 and recommended computed tomography coronary angiography (CTCA) as first line investigation for all patients with new onset symptoms. We implemented the guideline and audited downstream testing. METHODS: We undertook a retrospective search of the local radiology database from January 2017 to May 2018. RESULTS: Six-hundred and fifty-two patients underwent CTCA (mean age of 55 years, 330 were male). Thirty-four patients were found to have severe coronary artery disease (CAD), with 30 undergoing invasive coronary angiography (ICA) which confirmed severe CAD in 22, a yield of 73%.Fifty-eight patients were found to have moderate CAD on CTCA with 36 referred for ICA, of which, 33 attended and 18 were found to have severe CAD. Eighteen were referred for imaging stress tests and one was positive. The total yield of severe CAD at ICA was 55%. The majority of patients had normal coronary arteries. CONCLUSIONS: CTCA was an effective rule-out test for most patients. In patients that went on to have ICA, the overall yield of severe CAD was relatively high. This compares well with our previous audit applying the NICE 2010 guidelines which recommended ICA for all high probability patients wherein the yield of severe CAD was 30%.

CT coronary angiography: a paradigm shift for functional imaging tests.

The UK National Institute for Health and Care Excellence (NICE) have just updated their guideline on new-onset stable chest pain, recommending that all patients should be investigated with a CT coronary angiography (CTCA). In a separate guideline, NICE recommended CT fractional flow reserve (CT-FFR), to assess coronary stenoses, found on CTCA, stating that this would reduce the need for invasive coronary angiography and hence reduce cost. We discuss the evidence base for CT-FFR and emphasise that we already have established functional imaging tests, with extensive evidence base for efficacy and prognosis and that CT-FFR should be compared with this standard of care and not with the much more expensive and invasive fractional flow reserve undertaken during invasive coronary angiography.

Prognostic Value of Quantitative Stress Perfusion Cardiac Magnetic Resonance.

OBJECTIVES: This study sought to evaluate the prognostic usefulness of visual and quantitative perfusion cardiac magnetic resonance (CMR) ischemic burden in an unselected group of patients and to assess the validity of consensus-based ischemic burden thresholds extrapolated from nuclear studies. BACKGROUND: There are limited data on the prognostic value of assessing myocardial ischemic burden by CMR, and there are none using quantitative perfusion analysis. METHODS: Patients with suspected coronary artery disease referred for adenosine-stress perfusion CMR were included (n = 395; 70% male; age 58 ± 13 years). The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, aborted sudden death, and revascularization after 90 days. Perfusion scans were assessed visually and with quantitative analysis. Cross-validated Cox regression analysis and net reclassification improvement were used to assess the incremental prognostic value of visual or quantitative perfusion analysis over a baseline clinical model, initially as continuous covariates, then using accepted thresholds of ≥2 segments or ≥10% myocardium. RESULTS: After a median 460 days (interquartile range: 190 to 869 days) follow-up, 52 patients reached the primary endpoint. At 2 years, the addition of ischemic burden was found to increase prognostic value over a baseline model of age, sex, and late gadolinium enhancement (baseline model area under the curve [AUC]: 0.75; visual AUC: 0.84; quantitative AUC: 0.85). Dichotomized quantitative ischemic burden performed better than visual assessment (net reclassification improvement 0.043 vs. 0.003 against baseline model). CONCLUSIONS: This study was the first to address the prognostic benefit of quantitative analysis of perfusion CMR and to support the use of consensus-based ischemic burden thresholds by perfusion CMR for prognostic evaluation of patients with suspected coronary artery disease. Quantitative analysis provided incremental prognostic value to visual assessment and established risk factors, potentially representing an important step forward in the translation of quantitative CMR perfusion analysis to the clinical setting.

The safety, efficacy and cost-effectiveness of stress echocardiography in patients with high pretest probability of coronary artery disease.

OBJECTIVE: In this study, we assess the clinical and cost-effectiveness of stress echocardiography (SE), as well as the place of SE in patients with high pretest probability (PTP) of coronary artery disease (CAD). METHODS: We investigated 257 patients with no history of CAD, who underwent SE, and they had a PTP risk score >61% (high PTP). According to the National Institute for Health and Care Excellence guidance (NICE CG95, 2010), these patients should be investigated directly with an invasive coronary angiogram (ICA). We investigated those patients with SE initially and then with ICA when appropriate. Follow-up data with regard to Major Adverse Cardiac and Cerebrovascular Events (MACCE, defined as cardiovascular mortality, cerebrovascular accident (CVA), myocardial infarction (MI) and late revascularisation for acute coronary syndrome/unstable angina) were recorded for a period of 12 months following the SE. The tariff for SE and ICA is £300 and £1400, respectively. RESULTS: 106 patients had a positive SE (41.2%) and 61 of them (57.5%) had further investigation with ICA. 15 (24.6%) of these patients were revascularised. The average cost per patient for investigations was £654.09. If NICE guidance had been followed, the cost would have been significantly higher at £1400 (p<0.001). Overall, 5 MACCE (2.0%) were recorded; 4 (3.8%) in the group of positive SE (2 CVAs and 2 MIs) and 1 (0.7%) in the group of negative SE (1 CVA). There was no MI and no need for revascularisation in the negative SE group. CONCLUSION: Our approach to investigate patients who present with de novo chest pain and high PTP, with SE initially and subsequently with ICA when appropriate, reduces the cost significantly (£745.91 per patient) with a very low rate of MACCE. However, this study is underpowered to assess safety of SE.

The 2016 update to NICE CG95 guideline for the -investigation of new onset stable chest pain: more -innovation, but at a cost?

The National Institute for Health and Care Excellence (NICE) published an update on its guideline on chest pain of recent onset in 2016. The new guideline makes three key changes to the 2010 version. NICE recommend that the previously proposed pre-test probability risk score should no longer be used. They also recommend that a calcium score of zero should no longer be used to rule out coronary artery disease in patients with low pre-test probability. However, the most radical change is that NICE now recommend that all patients with new onset chest pain should be investigated with a computerised tomography coronary angiogram as a first-ine investigation. We discuss the recent trial evidence that has informed the NICE update and consider the impact of the new guidelines.

Prevalence of Subclinical Coronary Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic Risk Profile.

BACKGROUND: Studies in middle-age and older (masters) athletes with atherosclerotic risk factors for coronary artery disease report higher coronary artery calcium (CAC) scores compared with sedentary individuals. Few studies have assessed the prevalence of coronary artery disease in masters athletes with a low atherosclerotic risk profile. METHODS: We assessed 152 masters athletes 54.4±8.5 years of age (70% male) and 92 controls of similar age, sex, and low Framingham 10-year coronary artery disease risk scores with an echocardiogram, exercise stress test, computerized tomographic coronary angiogram, and cardiovascular magnetic resonance imaging with late gadolinium enhancement and a 24-hour Holter. Athletes had participated in endurance exercise for an average of 31±12.6 years. The majority (77%) were runners, with a median of 13 marathon runs per athlete. RESULTS: Most athletes (60%) and controls (63%) had a normal CAC score. Male athletes had a higher prevalence of atherosclerotic plaques of any luminal irregularity (44.3% versus 22.2%; P=0.009) compared with sedentary males, and only male athletes showed a CAC ≥300 Agatston units (11.3%) and a luminal stenosis ≥50% (7.5%). Male athletes demonstrated predominantly calcific plaques (72.7%), whereas sedentary males showed predominantly mixed morphology plaques (61.5%). The number of years of training was the only independent variable associated with increased risk of CAC >70th percentile for age or luminal stenosis ≥50% in male athletes (odds ratio, 1.08; 95% confidence interval, 1.01-1.15; P=0.016); 15 (14%) male athletes but none of the controls revealed late gadolinium enhancement on cardiovascular magnetic resonance imaging. Of these athletes, 7 had a pattern consistent with previous myocardial infarction, including 3(42%) with a luminal stenosis ≥50% in the corresponding artery. CONCLUSIONS: Most lifelong masters endurance athletes with a low atherosclerotic risk profile have normal CAC scores. Male athletes are more likely to have a CAC score >300 Agatston units or coronary plaques compared with sedentary males with a similar risk profile. The significance of these observations is uncertain, but the predominantly calcific morphology of the plaques in athletes indicates potentially different pathophysiological mechanisms for plaque formation in athletic versus sedentary men. Coronary plaques are more abundant in athletes, whereas their stable nature could mitigate the risk of plaque rupture and acute myocardial infarction.

The prognostic role of stress echocardiography in a contemporary population and the clinical significance of limited apical ischaemia.

INTRODUCTION: In this study, we aim to reassess the prognostic value of stress echocardiography (SE) in a contemporary population and to evaluate the clinical significance of limited apical ischaemia, which has not been previously studied. METHODS: We included 880 patients who underwent SE. Follow-up data with regards to MACCE (cardiac death, myocardial infarction, any repeat revascularisation and cerebrovascular accident) were collected over 12 months after the SE. Mortality data were recorded over 27.02 ± 4.6 months (5.5-34.2 months). We sought to investigate the predictors of MACCE and all-cause mortality. RESULTS: In a multivariable analysis, only the positive result of SE was predictive of MACCE (HR, 3.71; P = 0.012). The positive SE group was divided into 2 subgroups: (a) inducible ischaemia limited to the apical segments ('apical ischaemia') and (b) ischaemia in any other segments with or without apical involvement ('other positive'). The subgroup of patients with apical ischaemia had a significantly worse outcome compared to the patients with a negative SE (HR, 3.68; P = 0.041) but a similar outcome to the 'other positive' subgroup. However, when investigated with invasive coronary angiography, the prevalence of coronary artery disease (CAD) and their rate of revascularisation was considerably lower. Only age (HR, 1.07; P < 0.001) was correlated with all-cause mortality. CONCLUSION: SE remains a strong predictor of patients' outcome in a contemporary population. A positive SE result was the only predictor of 12-month MACCE. The subgroup of patients with limited apical ischaemia have similar outcome to patients with ischaemia in other segments despite a lower prevalence of CAD and a lower revascularisation rate.

Pre-test probability risk scores and their use in contemporary management of patients with chest pain: One year stress echo cohort study.

OBJECTIVES: To compare how patients with chest pain would be investigated, based on the two guidelines available for UK cardiologists, on the management of patients with stable chest pain. The UK National Institute of Clinical Excellence (NICE) guideline which was published in 2010 and the European society of cardiology (ESC) guideline published in 2013. Both guidelines utilise pre-test probability risk scores, to guide the choice of investigation. DESIGN: We undertook a large retrospective study to investigate the outcomes of stress echocardiography. SETTING: A large tertiary centre in the UK in a contemporary clinical practice. PARTICIPANTS: Two thirds of the patients in the cohort were referred from our rapid access chest pain clinics. RESULTS: We found that the NICE risk score overestimates risk by 20% compared to the ESC Risk score. We also found that based on the NICE guidelines, 44% of the patients presenting with chest pain, in this cohort, would have been investigated invasively, with diagnostic coronary angiography. Using the ESC guidelines, only 0.3% of the patients would be investigated invasively. CONCLUSION: The large discrepancy between the two guidelines can be easily reduced if NICE adopted the ESC risk score.

Comparison of ESC and NICE guidelines for patients with suspected coronary artery disease: evaluation of the pre-test probability risk scores in clinical practice.

The European Society of Cardiology (ESC) and UK National Institute for Health and Care Excellence (NICE) have recently published guidelines for investigating patients with suspected coronary artery disease (CAD). Both provide a risk score (RS) to assess the pre-test probability for CAD to guide clinicians to undertake the most effective investigation. The aim of the study was to establish whether there is a difference between the two RS models. We retrospectively reviewed records of 479 patients who presented to a UK district general hospital with chest pain between August 2011 and April 2013. The RS was calculated using ESC and NICE guidelines and compared. From the 479 patients, 277 (58%) were male and the mean age was 60 years. The mean RS was greater using NICE guidelines compared with ESC (66.3 vs 47.9%, 18.4% difference; p<0.0001). The difference in mean RS was smaller in patients with typical chest pain (13.0%). When we divided the cohort based on NICE criteria into 'high'- and 'low'-risk groups, the difference in the mean RS was 24.3% in the 'high'-risk group (p<0.001) compared with 2.8% in the 'low'-risk group. The UK NICE risk score model overestimates risk compared with the ESC model.

Comparison of clinical efficacy and cost of a cardiac imaging strategy versus a traditional exercise test strategy for the investigation of patients with suspected stable coronary artery disease.

We evaluated the clinical efficacy and cost of a cardiac imaging strategy versus a traditional exercise tolerance test (ETT) strategy for the investigation of suspected stable coronary artery disease (CAD). We retrospectively collected data of consecutive patients seen in rapid access chest pain clinics at 2 UK hospitals for a period of 12 months. Hospital A investigated patients by performing ETT. Hospital B investigated patients using cardiac imaging test; 483 patients from hospital A and 295 from hospital B were included. In hospital A, 209 patients (43.3%) had contraindication to ETT. Of those who had ETT, 151 (55.1%) had negative ETT, 68 (24.8%) had equivocal ETT, and 55 (20.1%) had positive ETT, of which 53 (96.4%) had invasive coronary angiography (ICA), and of these 23 (43.4%) had obstructive CAD. In hospital B, 26 patients (8.8%) with low pretest probability had calcium score and 3 (11.5%) were positive leading to computed tomography coronary angiography; 98 patients (33.2%) with intermediate pretest probability had computed tomography coronary angiography and 5 (5.1%) were positive; 77 patients (26.1%) had stress echocardiogram and 6 (7.8%) were positive; and 57 patients (19.3%) had myocardial perfusion scintigraphy and 11 (19.3%) were positive. Hospital A performed 127 ICA (26.3% of population) and 52 (40.9%) had obstructive CAD. Hospital B performed 63 ICA (21.4% of population) and 32 (50.8%) had obstructive CAD. The average cost per patient in hospital A was £566.6 ± 490.0 ($875 ± 758) and in hospital B was £487.9 ± 469.6 ($750 ± 725) (p <0.001). In conclusion, our results suggest that a cardiac imaging pathway leads to fewer ICA and a higher yield of obstructive CAD at lower cost per patient.