Measurement from arteriograms of regional myocardial bed size distal to any point in the coronary vascular tree for assessing anatomic area at risk

AbstractObjectives. To obtain the size of regional myocardial mass for individual coronary arteries in vivo.Background. The anatomic site of occlusion in a coronary artery does not predict the size of the risk area because location of the occlusion does not account for the size of the artery or of its dependent myocardial bed.Methods. Intracoronary radiolabeled microspheres were injected and coronary arteriograms were quantitatively analyzed by semiautomated methods. The coronary artery lumen areas and the sum of epicardial coronary artery branch lengths distal to the points where radiomicrospheres had been injected were determined from both in vivo and postmortem coronary arteriograms. Regional myocardial mass distal to the point of each microsphere injection was correlated with corresponding distal summed coronary branch lengths and with coronary artery lumen areas.Results. 1) Regional myocardial mass was closely and linearly related to sum of coronary artery branch lengths distal to any point in the coronary artery tree and therefore could be determined for any location on a coronary arteriogram. 2) The fraction of total left ventricular mass at risk distal to a stenosis could be determined from the corresponding fraction of total coronary artery tree length independently of the scale or X-ray magnification used to measure absolute branch lengths. 3) Cross-sectional lumen area at any point in the left coronary artery tree was closely related to the size of the dependent vascular bed with a curvilinear relation similar to that observed in humans with normal coronary arteriograms.Conclusions. On coronary arteriograms, the anatomic area at risk for myocardial infarction distal to any point in the coronary artery tree can be determined from the sum of distal coronary artery branch lengths. There is a curvilinear relation between coronary artery lumen area and dependent regional myocardial mass comparable to that in humans, reflecting fundamental physical principles underlying the structure of the coronary vascular tree

Subendocardial and Transmural Myocardial Ischemia: Clinical Characteristics, Prevalence, and Outcomes With and Without Revascularization

BACKGROUND: Subendocardial ischemia is commonly diagnosed but not quantified by imaging. OBJECTIVES: This study sought to define size and severity of subendocardial and transmural stress perfusion deficits, clinical associations, and outcomes. METHODS: Regional rest-stress perfusion in mL/min/g, coronary flow reserve, coronary flow capacity (CFC), relative stress flow, subendocardial stress-to-rest ratio and stress subendocardial-to-subepicardial ratio as percentage of left ventricle were measured by positron emission tomography (PET) with rubidium Rb 82 and dipyridamole stress in serial 6,331 diagnostic PETs with prospective 10-year follow-up for major adverse cardiac events with and without revascularization. RESULTS: Of 6,331 diagnostic PETs, 1,316 (20.7%) had severely reduced CFC with 41.4% having angina or ST-segment depression (STΔ) \u3e1 mm during hyperemic stress, increasing with size. For 5,015 PETs with no severe CFC abnormality, 402 (8%) had angina or STΔ during stress, and 82% had abnormal subendocardial perfusion with 8.7% having angina or STΔ \u3e1 mm during dipyridamole stress. Of 947 cases with stress-induced angina or STΔ \u3e1 mm, 945 (99.8%) had reduced transmural or subendocardial perfusion reflecting sufficient microvascular function to increase coronary blood flow and reduce intracoronary pressure, causing reduced subendocardial perfusion; only 2 (0.2%) had normal subendocardial perfusion, suggesting microvascular disease as the cause of the angina. Over 10-year follow-up (mean 5 years), severely reduced CFC associated with major adverse cardiac events of 44.4% compared to 8.8% for no severe CFC (unadjusted P \u3c 0.00001) and mortality of 15.2% without and 6.9% with revascularization (P \u3c 0.00002) confirmed by multivariable Cox regression modeling. For no severe CFC, mortality was 3% with and without revascularization (P = 0.90). CONCLUSIONS: Reduced subendocardial perfusion on dipyridamole PET without regional stress perfusion defects is common without angina, has low risk of major adverse cardiac events, reflecting asymptomatic nonobstructive diffuse coronary artery disease, or angina without stenosis. Severely reduced CFC causes angina in fewer than one-half of cases but incurs high mortality risk that is significantly reduced after revascularization

Prognostic value of microvascular resistance and its association to fractional flow reserve:a DEFINE-FLOW substudy

OBJECTIVE: This study aimed to evaluate the prognostic value of hyperemic microvascular resistance (HMR) and its relationship with hyperemic stenosis resistance (HSR) index and fractional flow reserve (FFR) in stable coronary artery disease. METHODS: This is a substudy of the DEFINE-FLOW cohort (NCT02328820), which evaluated the prognosis of lesions (n=456) after combined FFR and coronary flow reserve (CFR) assessment in a prospective, non-blinded, non-randomised, multicentre study in 12 centres in Europe and Japan. Participants (n=430) were evaluated by wire-based measurement of coronary pressure, flow and vascular resistance (ComboWire XT, Phillips Volcano, San Diego, California, USA). RESULTS: Mean FFR and CFR were 0.82±0.10 and 2.2±0.6, respectively. When divided according to FFR and CFR thresholds (above and below 0.80 and 2.0, respectively), HMR was highest in lesions with FFR>0.80 and CFR<2.0 (n=99) compared with lesions with FFR≤0.80 and CFR≥2.0 (n=68) (2.92±1.2 vs 1.91±0.64 mm Hg/cm/s, p<0.001). The FFR value was proportional to the ratio between HMR and the HMR+HSR (total resistance), 95% limits of agreement (−0.032; 0.019), bias (−0.003±0.02) and correlation (r(2)=0.98, p<0.0001). Cox regression model using HMR as continuous parameter for target vessel failure showed an HR of 1.51, 95% CI (0.9 to 2.4), p=0.10. CONCLUSIONS: Increased HMR was not associated with a higher rate of adverse clinical events, in this population of mainly stable patients. FFR can be equally well expressed as HMR/HMR+HSR, thereby providing an alternative conceptual formulation linking epicardial severity with microvascular resistance. TRIAL REGISTRATION NUMBER: NCT02328820

Continuum of vasodilator stress from rest to contrast medium to adenosine hyperemia for fractional flow reserve assessment

Objectives: This study compared the diagnostic performance with adenosine-derived fractional flow reserve (FFR) ≤0.8 of contrast-based FFR (cFFR), resting distal pressure (Pd)/aortic pressure (Pa), and the instantaneous wave-free ratio (iFR). Background: FFR objectively identifies lesions that benefit from medical therapy versus revascularization. However, FFR requires maximal vasodilation, usually achieved with adenosine. Radiographic contrast injection causes submaximal coronary hyperemia. Therefore, intracoronary contrast could provide an easy and inexpensive tool for predicting FFR. Methods: We recruited patients undergoing routine FFR assessment and made paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, cFFR, and FFR). Contrast medium and dose were per local practice, as was the dose of intracoronary adenosine. Operators were encouraged to perform both intracoronary and intravenous adenosine assessments and a final drift check to assess wire calibration. A central core lab analyzed blinded pressure tracings in a standardized fashion. Results: A total of 763 subjects were enrolled from 12 international centers. Contrast volume was 8 ± 2 ml per measurement, and 8 different contrast media were used. Repeated measurements of each metric showed a bias &lt;0.005, but a lower SD (less variability) for cFFR than resting indexes. Although Pd/Pa and iFR demonstrated equivalent performance against FFR ≤0.8 (78.5% vs. 79.9% accuracy; p = 0.78; area under the receiver-operating characteristic curve: 0.875 vs. 0.881; p = 0.35), cFFR improved both metrics (85.8% accuracy and 0.930 area; p &lt; 0.001 for each) with an optimal binary threshold of 0.83. A hybrid decision-making strategy using cFFR required adenosine less often than when based on either Pd/Pa or iFR. Conclusions: cFFR provides diagnostic performance superior to that of Pd/Pa or iFR for predicting FFR. For clinical scenarios or health care systems in which adenosine is contraindicated or prohibitively expensive, cFFR offers a universal technique to simplify invasive coronary physiological assessments. Yet FFR remains the reference standard for diagnostic certainty as even cFFR reached only ∼85% agreement

Coronary Flow Capacity and Survival Prediction after Revascularization: Physiological Basis and Clinical Implications

BACKGROUND AND AIMS: Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization. METHODS: Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0. RESULTS: Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P \u3c .001), more so after bypass surgery than percutaneous coronary interventions (P \u3c .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P \u3c .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025). CONCLUSIONS: Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization