Rethinking False Positive Exercise Electrocardiographic Stress Tests by Assessing Coronary Microvascular Function.

BACKGROUND: Exercise electrocardiographic stress testing (EST) has historically been validated against the demonstration of obstructive coronary artery disease. However, myocardial ischemia can occur because of coronary microvascular dysfunction (CMD) in the absence of obstructive coronary artery disease. OBJECTIVES: The aim of this study was to assess the specificity of EST to detect an ischemic substrate against the reference standard of coronary endothelium-independent and endothelium-dependent microvascular function in patients with angina with nonobstructive coronary arteries (ANOCA). METHODS: Patients with ANOCA underwent invasive coronary physiological assessment using adenosine and acetylcholine. CMD was defined as impaired endothelium-independent and/or endothelium-dependent function. EST was performed using a standard Bruce treadmill protocol, with ischemia defined as the appearance of ≥0.1-mV ST-segment depression 80 ms from the J-point on electrocardiography. The study was powered to detect specificity of ≥91%. RESULTS: A total of 102 patients were enrolled (65% women, mean age 60 ± 8 years). Thirty-two patients developed ischemia (ischemic group) during EST, whereas 70 patients did not (nonischemic group); both groups were phenotypically similar. Ischemia during EST was 100% specific for CMD. Acetylcholine flow reserve was the strongest predictor of ischemia during exercise. Using endothelium-independent and endothelium-dependent microvascular dysfunction as the reference standard, the false positive rate of EST dropped to 0%. CONCLUSIONS: In patients with ANOCA, ischemia on EST was highly specific of an underlying ischemic substrate. These findings challenge the traditional belief that EST has a high false positive rate.

Assessment and Management of Ischaemic Heart Disease in Non-Cardiac Surgery.

In the setting of non-cardiac surgery, cardiac complications contribute to over a third of perioperative deaths. With over 230 million major surgeries performed annually, and an increasing prevalence of cardiovascular risk factors and ischaemic heart disease, the incidence of perioperative myocardial infarction is also rising. The recent European Society of Cardiology guidelines on cardiovascular risk in noncardiac surgery elevated practices aiming to identify those at most risk, including biomarker monitoring and stress testing. However the current evidence base on if, and how, the risk of cardiac events can be modified is lacking. This review focuses on patient, surgical and cardiac risk assessment, as well as exploring the data on perioperative revascularization and other risk-reduction strategies.

Coronary Wave Intensity Analysis as an Invasive and Vessel-Specific Index of Myocardial Viability.

BACKGROUND: Coronary angiography and viability testing are the cornerstones of diagnosing and managing ischemic cardiomyopathy. At present, no single test serves both needs. Coronary wave intensity analysis interrogates both contractility and microvascular physiology of the subtended myocardium and therefore has the potential to fulfil the goal of completely assessing coronary physiology and myocardial viability in a single procedure. We hypothesized that coronary wave intensity analysis measured during coronary angiography would predict viability with a similar accuracy to late-gadolinium-enhanced cardiac magnetic resonance imaging. METHODS: Patients with a left ventricular ejection fraction ≤40% and extensive coronary disease were enrolled. Coronary wave intensity analysis was assessed during cardiac catheterization at rest, during adenosine-induced hyperemia, and during low-dose dobutamine stress using a dual pressure-Doppler sensing coronary guidewire. Scar burden was assessed with cardiac magnetic resonance imaging. Regional left ventricular function was assessed at baseline and 6-month follow-up after optimization of medical-therapy±revascularization, using transthoracic echocardiography. The primary outcome was myocardial viability, determined by the retrospective observation of functional recovery. RESULTS: Forty participants underwent baseline physiology, cardiac magnetic resonance imaging, and echocardiography, and 30 had echocardiography at 6 months; 21/42 territories were viable on follow-up echocardiography. Resting backward compression wave energy was significantly greater in viable than in nonviable territories (-5240±3772 versus -1873±1605 W m-2 s-1, P<0.001), and had comparable accuracy to cardiac magnetic resonance imaging for predicting viability (area under the curve 0.812 versus 0.757, P=0.649); a threshold of -2500 W m-2 s-1 had 86% sensitivity and 76% specificity. CONCLUSIONS: Backward compression wave energy has accuracy similar to that of late-gadolinium-enhanced cardiac magnetic resonance imaging in the prediction of viability. Coronary wave intensity analysis has the potential to streamline the management of ischemic cardiomyopathy, in a manner analogous to the effect of fractional flow reserve on the management of stable angina.

The Impact of a Dedicated Chronic Total Occlusion PCI Program on Heart Team Decision Making.

BACKGROUND: Guidelines endorse a heart team (HT) approach to standardize the decision-making process for patients with complex coronary artery disease (CAD). With percutaneous treatment options for complex CAD increasing, we hypothesized that practice had changed over the past decade-and that more individuals, previously deemed too high risk for intervention, would now be referred for either surgical or percutaneous revascularization. METHODS: This observational study was conducted at St Thomas' Hospital (London, United Kingdom). All patients discussed at HT meetings were recorded and treatment recommendations audited. A subset of historic cases was selected for blinded, repeat discussion. RESULTS: From April 2018 to 2019, a total of 52 HT meetings discussing 375 cases were held. Patients tended to be male, with a majority demonstrating multivessel CAD in the context of preserved left ventricular function. SYNTAX scores were balanced across the tertiles. Thirty-five percent of patients had at least 1 chronic total occlusion (mean J-CTO, 3 [interquartile range, 2-3]), affecting the right coronary artery in 60%. Fifteen historic patients with isolated CTOs were re-presented an average of 8 years later; only 3 patients received the same outcome, with 80% now receiving a recommendation for revascularization over medical therapy. CONCLUSIONS: A dedicated program supporting complex coronary intervention is associated with a change in treatment recommendations issued by the local HT. In line with international guidelines, this might indicate that any complex or multivessel CAD should be discussed at HT meetings with, ideally, the presence of CTO operators.

In vivo morphologic comparison of saphenous vein grafts and native coronary arteries following non-ST elevation myocardial infarction.

OBJECTIVE: This study aimed to assess the pathophysiological differences between saphenous vein grafts (SVG) and native coronary arteries (NCA) following presentation with non-ST elevated myocardial infarction (NSTEMI). BACKGROUND: There is accelerated pathogenesis of de novo coronary disease in harvested SVG following coronary artery bypass (CABG) surgery, which contributes to both early and late graft failure, and is also causal in adverse outcomes following vein graft PCI. However in vivo assessment, with OCT imaging, comparing the differences between vein grafts and NCAs has not previously been performed. METHODS: We performed a retrospective, observational, analysis in patients who underwent PCI with adjunctive OCT imaging following presentation with NSTEMI, where the infarct-related artery (IRA) was either in an SVG or NCA. RESULTS: A total of 1550 OCT segments was analysed from thirty patients with a mean age of 66.3 (±9.0) years were included. The mean graft age of 13.9 (±5.6) years in the SVG group. OCT imaging showed that the SVG group had evidence of increased lipid pool burden (lipid pool quadrants, 2.1 vs 2.7; p = 0.021), with a reduced fibro-atheroma cap-thickness in the SVG group (45.0 µm vs 38.5 µm; p = 0.05) and increased burden of calcification (calcified lesion length = 0.4 mm vs 1.8 mm; p = 0.007; calcified quadrants = 0.2 vs 0.9; p = 0.001; arc of superficial calcium deposits = 11.6° vs 50.9°; p = 0.007) when compared to NCA. CONCLUSION: This OCT study has demonstrated that vein grafts have a uniquely atherogenic environment which leads to the development of calcified, lipogenic, thin-capped fibro-atheroma's, which may be pivotal in the increased, acute and chronic graft failure rate, and may underpin the increased adverse outcomes following vein graft PCI.

Changes in contractility determine coronary haemodynamics in dyssynchronous left ventricular heart failure, not vice versa.

BACKGROUND: Biventricular pacing has been shown to increase both cardiac contractility and coronary flow acutely but the causal relationship is unclear. We hypothesised that changes in coronary flow are secondary to changes in cardiac contractility. We sought to examine this relationship by modulating coronary flow and cardiac contractility. METHODS: Contractility and lusitropy were altered by varying the location of pacing in 8 patients. Coronary autoregulation was transiently disabled with intracoronary adenosine. Simultaneous coronary flow velocity, coronary pressure and left ventricular pressure data were measured in the different pacing settings with and without hyperaemia and wave intensity analysis performed. RESULTS: Multisite pacing was effective at altering left ventricular contractility and lusitropy (pos. dp/dtmax -13% to +10% and neg. dp/dtmax -15% to +17% compared to baseline). Intracoronary adenosine decreased microvascular resistance (362.5 mm Hg/s/m to 156.7 mm Hg/s/m, p < 0.001) and increased LAD flow velocity (22 cm/s vs 45 cm/s, p < 0.001) but did not acutely change contractility or lusitropy. The magnitude of the dominant accelerating wave, the Backward Expansion Wave, was proportional to the degree of contractility as well as lusitropy (r = 0.47, p < 0.01 and r = -0.50, p < 0.01). Perfusion efficiency (the proportion of accelerating waves) increased at hyperaemia (76% rest vs 81% hyperaemia, p = 0.04). Perfusion efficiency correlated with contractility and lusitropy at rest (r = 0.43 & -0.50 respectively, p = 0.01) and hyperaemia (r = 0.59 & -0.6, p < 0.01). CONCLUSIONS: Acutely increasing coronary flow with adenosine in patients with systolic heart failure does not increase contractility. Changes in coronary flow with biventricular pacing are likely to be a consequence of enhanced cardiac contractility from resynchronization and not vice versa.

Ischemic preconditioning-an unfulfilled promise.

Myocardial reperfusion injury has been identified as a key determinant of myocardial infarct size in patients undergoing percutaneous or surgical interventions. Although the molecular mechanisms underpinning reperfusion injury have been elucidated, attempts at translating this understanding into clinical benefit for patients undergoing cardiac interventions have produced mixed results. Ischemic conditioning has been applied before, during, or after an ischemic insult to the myocardium and has taken the form of local induction of ischemia or ischemia of distant tissues. Clinical studies have confirmed the safety of differing conditioning techniques, but the benefit of such techniques in reducing hard clinical event rates has produced mixed results. The aim of this article is to review the role of ischemic conditioning in patients undergoing percutaneous and surgical coronary revascularization.

Ischemic burden by 3-dimensional myocardial perfusion cardiovascular magnetic resonance: comparison with myocardial perfusion scintigraphy.

BACKGROUND: The extent and severity of ischemia on myocardial perfusion scintigraphy (MPS) is commonly used to risk-stratify patients with coronary artery disease. Estimation of ischemic burden by cardiovascular magnetic resonance (CMR) with conventional 2-dimensional myocardial perfusion methods is limited by incomplete cardiac coverage. More recently developed 3-dimensional (3D) myocardial perfusion CMR, however, provides whole-heart coverage. The aim of this study was to compare ischemic burden on 3D myocardial perfusion CMR with (99m)Tc-tetrofosmin MPS. METHODS AND RESULTS: Forty-five patients who had undergone clinically indicated MPS underwent rest and adenosine stress 3D myocardial perfusion and late gadolinium enhancement CMR. Summed stress and rest scores were calculated for MPS and CMR using a 17-segment model and expressed as a percentage of the maximal possible score. Ischemic burden was defined as the difference between stress and rest scores. 3D myocardial perfusion CMR and MPS agreed in 38 of the 45 patients for the detection of any inducible ischemia. The mean ischemic burden for MPS and CMR was similar (7.5±8.9% versus 6.8±9.5%, respectively, P=0.82) with a strong correlation between techniques (rs=0.70, P<0.001). In a subset of 33 patients who underwent clinically indicated invasive coronary angiography, sensitivities and specificities of the 2 techniques to detect angiographic coronary artery disease were similar (McNemar P=0.45). CONCLUSIONS: 3D myocardial perfusion CMR is an alternative to MPS for detecting the presence and rating the severity of ischemia.

Coronary and microvascular physiology during intra-aortic balloon counterpulsation.

OBJECTIVES: This study sought to identify the effect of coronary autoregulation on myocardial perfusion during intra-aortic balloon pump (IABP) therapy. BACKGROUND: IABP is the most commonly used circulatory support device, although its efficacy in certain scenarios has been questioned. The impact of alterations in microvascular function on IABP efficacy has not previously been evaluated in humans. METHODS: Thirteen patients with ischemic cardiomyopathy (left ventricular ejection fraction: 34 ± 8%) undergoing percutaneous coronary intervention were recruited. Simultaneous intracoronary pressure and Doppler-flow measurements were undertaken in the target vessel following percutaneous coronary intervention, during unassisted and IABP-assisted conditions. Coronary autoregulation was modulated by the use of intracoronary adenosine, inducing maximal hyperemia. Wave intensity analysis characterized the coronary wave energies associated with balloon counterpulsation. RESULTS: Two unique diastolic coronary waves were temporally associated with IABP device use; a forward compression wave and a forward expansion wave caused by inflation and deflation, respectively. During basal conditions, IABP therapy increased distal coronary pressure (82.4 ± 16.1 vs. 88.7 ± 17.8 mm Hg, p = 0.03), as well as microvascular resistance (2.32 ± 0.52 vs. 3.27 ± 0.41 mm Hg cm s(-1), p = 0.001), with no change in average peak velocity (30.6 ± 12.0 vs. 26.6 ± 11.3 cm s(-1), p = 0.59). When autoregulation was disabled, counterpulsation caused an increase in average peak velocity (39.4 ± 10.5 vs. 44.7 ± 17.5 cm s(-1), p = 0.002) that was linearly related with IABP-forward compression wave energy (R(2) = 0.71, p = 0.001). CONCLUSIONS: Autoregulation ameliorates the effect of IABP on coronary flow. However, during hyperemia, IABP augments myocardial perfusion, principally due to a diastolic forward compression wave caused by balloon inflation, suggesting IABP would be of greatest benefit when microcirculatory reserve is exhausted.

Wave speed in human coronary arteries is not influenced by microvascular vasodilation: implications for wave intensity analysis.

Wave intensity analysis and wave separation are powerful tools for interrogating coronary, myocardial and microvascular physiology. Wave speed is integral to these calculations and is usually estimated by the single-point technique (SPc), a feasible but as yet unvalidated approach in coronary vessels. We aimed to directly measure wave speed in human coronary arteries and assess the impact of adenosine and nitrate administration. In 14 patients, the transit time Δt between two pressure signals was measured in angiographically normal coronary arteries using a microcatheter equipped with two high-fidelity pressure sensors located Δs = 5 cm apart. Simultaneously, intracoronary pressure and flow velocity were measured with a dual-sensor wire to derive SPc. Actual wave speed was calculated as DNc = Δs/Δt. Hemodynamic signals were recorded at baseline and during adenosine-induced hyperemia, before and after nitroglycerin administration. The energy of separated wave intensity components was assessed using SPc and DNc. At baseline, DNc equaled SPc (15.9 ± 1.8 vs. 16.6 ± 1.5 m/s). Adenosine-induced hyperemia lowered SPc by 40 % (p < 0.005), while DNc remained unchanged, leading to marked differences in respective separated wave energies. Nitroglycerin did not affect DNc, whereas SPc transiently fell to 12.0 ± 1.2 m/s (p < 0.02). Human coronary wave speed is reliably estimated by SPc under resting conditions but not during adenosine-induced vasodilation. Since coronary wave speed is unaffected by microvascular dilation, the SPc estimate at rest can serve as surrogate for separating wave intensity signals obtained during hyperemia, thus greatly extending the scope of WIA to study coronary physiology in humans.

Validation of dynamic 3-dimensional whole heart magnetic resonance myocardial perfusion imaging against fractional flow reserve for the detection of significant coronary artery disease.

OBJECTIVES: The goal of this study was to determine the diagnostic accuracy of dynamic 3-dimensional (3D) whole heart myocardial perfusion cardiovascular magnetic resonance (CMR) against invasively determined fractional flow reserve (FFR) and to establish the correlation between myocardium at risk defined by using the invasive Duke Jeopardy Score (DJS) and noninvasive 3D whole heart myocardial perfusion CMR. BACKGROUND: 3D whole heart myocardial perfusion CMR overcomes the limited spatial coverage of conventional two-dimensional perfusion CMR methods and allows estimation of the extent of ischemia. The method has shown good diagnostic accuracy for the detection of coronary artery disease (CAD) as defined by using quantitative coronary angiography. However, quantitative coronary angiography does not provide a functional assessment of CAD as available from pressure wire-derived FFR. In the catheter laboratory, the DJS can complement FFR to estimate the myocardium at risk. METHODS: Fifty-three patients referred for angiography underwent rest and adenosine stress 3D whole heart myocardial perfusion CMR at 3-T. Perfusion was scored visually on a patient and coronary territory basis, and ischemic burden was calculated by quantitative segmentation of the volume of hypoenhancement. FFR was measured in vessels with ≥50% severity stenosis and an FFR <0.75 considered as hemodynamically significant. The DJS was calculated from the coronary angiograms to quantify the myocardium at risk. RESULTS: FFR was measured in 64 of 159 coronary vessels, and 39 had an FFR <0.75. Sensitivity, specificity, and diagnostic accuracy of CMR for the detection of significant CAD were 91%, 90%, and 91%, on a patient basis and 79%, 92%, and 88%, respectively, by coronary territory. There was a strong correlation between the DJS and ischemic burden on CMR (p < 0.0001; Pearson's r = 0.82). CONCLUSIONS: 3D whole heart myocardial perfusion CMR accurately detects functionally significant CAD as defined by using FFR and provides an assessment of ischemic burden in agreement with the invasive DJS. The accurate detection of significant CAD combined with an estimation of ischemic burden by using 3D myocardial perfusion CMR holds promise for noninvasive guidance of therapy and risk stratification of patients with CAD.

High-resolution magnetic resonance myocardial perfusion imaging at 3.0-Tesla to detect hemodynamically significant coronary stenoses as determined by fractional flow reserve.

OBJECTIVES: The objective of this study was to compare visual and quantitative analysis of high spatial resolution cardiac magnetic resonance (CMR) perfusion at 3.0-T against invasively determined fractional flow reserve (FFR). BACKGROUND: High spatial resolution CMR myocardial perfusion imaging for the detection of coronary artery disease (CAD) has recently been proposed but requires further clinical validation. METHODS: Forty-two patients (33 men, age 57.4 ± 9.6 years) with known or suspected CAD underwent rest and adenosine-stress k-space and time sensitivity encoding accelerated perfusion CMR at 3.0-T achieving in-plane spatial resolution of 1.2 × 1.2 mm(2). The FFR was measured in all vessels with >50% severity stenosis. Fractional flow reserve <0.75 was considered hemodynamically significant. Two blinded observers visually interpreted the CMR data. Separately, myocardial perfusion reserve (MPR) was estimated using Fermi-constrained deconvolution. RESULTS: Of 126 coronary vessels, 52 underwent pressure wire assessment. Of these, 27 lesions had an FFR <0.75. Sensitivity and specificity of visual CMR analysis to detect stenoses at a threshold of FFR <0.75 were 0.82 and 0.94 (p < 0.0001), respectively, with an area under the receiver-operator characteristic curve of 0.92 (p < 0.0001). From quantitative analysis, the optimum MPR to detect such lesions was 1.58, with a sensitivity of 0.80, specificity of 0.89 (p < 0.0001), and area under the curve of 0.89 (p < 0.0001). CONCLUSIONS: High-resolution CMR MPR at 3.0-T can be used to detect flow-limiting CAD as defined by FFR, using both visual and quantitative analyses.

Impact of measuring fractional flow reserve on decision-making in the cath lab in a cohort of patients being considered for coronary revascularization.

BACKGROUND: Fractional flow reserve (FFR) is an accepted standard to detect the functional significance of coronary stenoses. Recent trials suggest that revascularization of moderate coronary stenoses can be safely deferred if the FFR is > or = 0.75 and FFR can be used to guide therapy in multivessel disease. AIM: In a cohort of patients with moderate angiographic coronary disease, we sought to examine the influence of FFR on lesion revascularization and the impact of multivessel FFR assessment on revascularization strategy. METHODS AND RESULTS: Patients with FFR measurements taken between April 2005 to October 2007 were included. Out of 300 cases performed in this time, 264 patients were included. Patients were 62 +/- 11 years and 1.3 +/- 0.54 vessels were examined per case. 92.7% of lesions with a FFR < 0.75 underwent revascularizati on an d 93% of lesions with a FFR > or = 0.75 had intervention deferred. FFR was 0.71 +/- 0.07 in the revascularization group (9 coronary artery bypass graft surgery, 64 percutaneous coronary interventions) and 0.86 +/- 0.06 in the deferred group (p < 0.001). Overall, 75% of patients avoided revascularization of at least one vessel on the basis of the FFR. CONCLUSIONS: Measurement of FFR is clinically useful with a high impact on clinical decision-making in the catheterization laboratory. FFR can be used to reclassify patients with multivessel stenoses, reducing the need for revascularization in the majority of cases.