Intracoronary electrocardiogram detects coronary microvascular dysfunction and ischemia in patients with no obstructive coronary arteries disease.

BACKGROUND: Coronary microvascular dysfunction (CMD) is the leading cause of ischemia with no obstructive coronary arteries disease (INOCA) disease. Diagnosis of CMD relies on surrogate physiological indices without objective proof of ischemia. OBJECTIVES: Intracoronary electrocardiogram (icECG) derived hyperemic indices may accurately and objectively detect CMD and reversible ischemia in related territory. METHODS: INOCA patients with proven ischemia by myocardial perfusion scan (MPS) and completely normal coronary arteries underwent simultaneous intracoronary electrophysiological (icECG) and physiological (intracoronary Doppler) assessment in all 3 coronary arteries during rest and under adenosine induced hyperemia. RESULTS: Sixty vessels in 21 patients were included in the final analysis. All patients had at least one vessel with abnormal CFR. 41 vessels had CMD (CFR < 2.5), of which 26 had increased microvascular resistance (structural CMD, HMR > 1.9 mmHg.cm-1.s) and 15 vessels had CMD (CFR < 2.5) with normal microvascular resistance (functional CMD, HMR <= 1.9 mmHg.cm-1.s). Only one-third of the patients (n = 7) had impaired CFR < 2.5 in all 3 epicardial arteries. Absolute ST shift between hyperemia and rest (∆ST) has shown the best diagnostic performance for ischemia (cut-off 0.10 mV, sensitivity: 95%, specificity: 72%, accuracy: 80%, AUC: 0.860) outperforming physiological indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002). CONCLUSIONS: In INOCA patients, CMD involves coronary artery territories heterogeneously. icECG can accurately detect CMD causing perfusion abnormalities in patients with INOCA outperforming physiological CMD markers, by demonstrating actual ischemia instead of predicting the likelihood of inducible ischemia based on violated surrogate thresholds of blunted flow reserve or increased minimum microvascular resistance. CONDENSED ABSTRACT: In 21 INOCA patients with coronary microvascular dysfunction (CMD) and myocardial perfusion scan proved ischemia, hyperemic indices of intracoronary electrocardiogram (icECG) have accurately detected vessel-specific CMD and resulting perfusion abnormalities & ischemia, outperforming invasive hemodynamic indices. Absolute ST shift between hyperemia and rest (∆ST) has shown the best classification performance for ischemia in no Obstructive Coronary Arteries (AUC: 0.860) outperforming Doppler derived CMD indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002).icECG can be used to diagnose CMD causing perfusion defects by demonstrating actual reversible ischemia at vessel-level during the initial CAG session, obviating the need for further costly ischemia tests. CLINICALTRIALS: GOV: NCT05471739.

Primary versus iatrogenic (post-PCI) coronary microvascular dysfunction: a wire-based multimodal comparison.

BACKGROUND: Although there are studies examining each one separately, there are no data in the literature comparing the magnitudes of the iatrogenic, percutaneous coronary intervention (PCI)-induced, microvascular dysfunction (Type-4 CMD) and coronary microvascular dysfunction (CMD) in the setting of ischaemia in non-obstructed coronary arteries (INOCA) (Type-1 CMD). OBJECTIVES: We aimed to compare the characteristics of Type-1 and Type-4 CMD subtypes using coronary haemodynamic (resistance and flow-related parameters), thermodynamic (wave energy-related parameters) and hyperemic ECG changes. METHODS: Coronary flow reserve (CFR) value of <2.5 was defined as CMD in both groups. Wire-based multimodal perfusion markers were comparatively analysed in 35 patients (21 INOCA/CMD and 14 CCS/PCI) enrolled in NCT05471739 study. RESULTS: Both groups had comparably blunted CFR values per definition (2.03±0.22 vs 2.11±0.37; p: 0.518) and similar hyperemic ST shift in intracoronary ECG (0.16±0.09 vs 0.18±0.07 mV; p: 0.537). While the Type-1 CMD was characterised with impaired hyperemic blood flow acceleration (46.52+12.83 vs 68.20+28.63 cm/s; p: 0.017) and attenuated diastolic microvascular decompression wave magnitudes (p=0.042) with higher hyperemic microvascular resistance (p<0.001), Type-4 CMD had blunted CFR mainly due to higher baseline flow velocity due to post-occlusive reactive hyperemia (33.6±13.7 vs 22.24±5.3 cm/s; p=0.003). CONCLUSIONS: The perturbations in the microvascular milieu seen in CMD in INOCA setting (Type-1 CMD) seem to be more prominent than that of seen following elective PCI (Type-4 CMD), although resulting reversible ischaemia is equally severe in the downstream myocardium.

Coronary microcirculation in nonculprit vessel territory in reperfused acute myocardial infarction.

BACKGROUND: There is an ongoing debate on the extension of reperfusion-related microvascular damage (MVD) throughout the remote noninfarcted myocardial regions in patients with ST-elevation myocardial infarction (STEMI) that undergo primary percutaneous intervention (pPCI). The aim of this study was to elucidate the impact of reperfusion on remote microcirculatory territory by analyzing hemodynamic alterations in the nonculprit-vessel in relation to reperfusion. METHODS: A total of 20 patients with STEMI undergoing pPCI were included. Peri-reperfusion temporal changes in hemodynamic parameters were obtained in angiographically normal nonculprit vessels before and 1-h after reopening of the culprit vessel. Intracoronary pressure and flow velocity data were compared using pairwise analyses (before and 1-h after reperfusion). RESULTS: In the non-culprit vessel, compared to the pre-reperfusion state, mean resting average peak velocity (33.4 ± 9.4 to 25.0 ± 4.9 cm/s, P < 0.001) and mean hyperemic average peak velocity (53.5 ± 14.4 to 42.1 ± 10.66 cm/s, P = 0.001) significantly decreased; whereas baseline (3.2 ± 1.0 to 4.0 ± 1.0 mmHg.cm-1.s, P < 0.001) and hyperemic microvascular resistance (HMR) (1.9 ± 0.6 to 2.4 ± 0.7 mmHg.cm-1.s, P < 0.001) and mean zero flow pressure (Pzf) values (32.5 ± 6.9 to 37.6 ± 8.3 mmHg, P = 0.003) significantly increased 1-h after reperfusion. In particular, the magnitude of changes in HMR and Pzf values following reperfusion were more prominent in patients with larger infarct size and with higher extent of MVD in the culprit vessel territory. CONCLUSION: Reperfusion-related microvascular injury extends to involve remote myocardial territory in relation to the magnitude of the adjacent infarction and infarct-zone MVD. (GUARD Clinical TrialsNCT02732080).

Gradual Versus Abrupt Reperfusion During Primary Percutaneous Coronary Interventions in ST-Segment-Elevation Myocardial Infarction (GUARD).

Background Intramyocardial edema and hemorrhage are key pathological mechanisms in the development of reperfusion-related microvascular damage in ST-segment-elevation myocardial infarction. These processes may be facilitated by abrupt restoration of intracoronary pressure and flow triggered by primary percutaneous coronary intervention. We investigated whether pressure-controlled reperfusion via gradual reopening of the infarct-related artery may limit microvascular injury in patients undergoing primary percutaneous coronary intervention. Methods and Results A total of 83 patients with ST-segment-elevation myocardial infarction were assessed for eligibility and 53 who did not meet inclusion criteria were excluded. The remaining 30 patients with totally occluded infarct-related artery were randomized to the pressure-controlled reperfusion with delayed stenting (PCRDS) group (n=15) or standard primary percutaneous coronary intervention with immediate stenting (IS) group (n=15) (intention-to-treat population). Data from 5 patients in each arm were unsuitable to be included in the final analysis. Finally, 20 patients undergoing primary percutaneous coronary intervention who were randomly assigned to either IS (n=10) or PCRDS (n=10) were included. In the PCRDS arm, a 1.5-mm balloon was used to achieve initial reperfusion with thrombolysis in myocardial infarction grade 3 flow and, subsequently, to control distal intracoronary pressure over a 30-minute monitoring period (MP) until stenting was performed. In both study groups, continuous assessment of coronary hemodynamics with intracoronary pressure and Doppler flow velocity was performed, with a final measurement of zero flow pressure (primary end point of the study) at the end of a 60-minute MP. There were no complications associated with IS or PCRDS. PCRDS effectively led to lower distal intracoronary pressures than IS over 30 minutes after reperfusion (71.2±9.37 mm Hg versus 90.13±12.09 mm Hg, P=0.001). Significant differences were noted between study arms in the microcirculatory response over MP. Microvascular perfusion progressively deteriorated in the IS group and at the end of MP, and hyperemic microvascular resistance was significantly higher in the IS arm as compared with the PCDRS arm (2.83±0.56 mm Hg.s.cm-1 versus 1.83±0.53 mm Hg.s.cm-1, P=0.001). The primary end point (zero flow pressure) was significantly lower in the PCRDS group than in the IS group (41.46±17.85 mm Hg versus 76.87±21.34 mm Hg, P=0.001). In the whole study group (n=20), reperfusion pressures measured at predefined stages in the early reperfusion period showed robust associations with zero flow pressure values measured at the end of the 1-hour MP (immediately after reperfusion: r=0.782, P<0.001; at the 10th minute: r=0.796, P<0.001; and at the 20th minute: r=0.702, P=0.001) and peak creatine kinase MB level (immediately after reperfusion: r=0.653, P=0.002; at the 10th minute: r=0.597, P=0.007; and at the 20th minute: r=0.538, P=0.017). Enzymatic myocardial infarction size was lower in the PCRDS group than in the IS group with peak troponin T (5395±2991 ng/mL versus 8874±1927 ng/mL, P=0.006) and creatine kinase MB (163.6±93.4 IU/L versus 542.2±227.4 IU/L, P<0.001). Conclusions In patients with ST-segment-elevation myocardial infarction, pressure-controlled reperfusion of the culprit vessel by means of gradual reopening of the occluded infarct-related artery (PCRDS) led to better-preserved coronary microvascular integrity and smaller myocardial infarction size, without an increase in procedural complications, compared with IS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02732080.

Development of a novel CT-derived measure of cardiovascular health: the CT aortic stiffness index (CTASI).

AIMS: Aortic stiffness, measured as aortic pulse wave velocity (PWV), is a powerful predictor of cardiovascular health but is difficult to accurately obtain non-invasively. This study sought to develop a novel CT aortic stiffness index (CTASI) which incorporates both anatomical (calcification) and physiological (distensibility) aspects of aortic health. METHODS: Invasive PWV and CT scans were obtained for 80 patients undergoing TAVI (cohort 1). CT data alone were obtained from an additional 238 patients (cohort 2). Aortic calcification was quantified using a modified Agatston's methodology. Distensibility-PWV was calculated from minimum and maximum ascending aorta areas. Linear regression of these values was used to construct CTASI from cohort 1. CTASI was then calculated for cohort 2 who were prospectively followed-up. RESULTS: CTASI correlated with invasive PWV (rho = 0.47, p < 0.01) with a higher correlation coefficient than distensibility-PWV (rho = 0.35, p < 0.01) and aortic calcification (rho = 0.36, p < 0.01). Compared to invasive PWV, CTASI had a good accuracy as a diagnostic test (AOC 0.72 [95% CI 0.61-0.84]), superior to aortic calcification and distensibility-PWV alone (χ2 = 0.82, p = 0.02). There were 61 deaths during a median follow-up of 771 days (95% CI 751.4-790.5). CTASI was able to predict 1-year mortality (OR 2.58, 95% CI 1.18-5.61, p = 0.02) and Kaplan-Meier survival (log-rank p = 0.03). CONCLUSION: CTASI is a stronger measure of aortic stiffness than aortic calcification or distensibility alone. Given the prolific use of CT scanning for assessing coronary and vascular disease, the additional calculation of CTASI during these scans could provide an important direct measurement of vascular health and guide pharmacological therapy.

Electrification of a Guidewire to Assist in Crossing an Aortic Coarctation (The BEACON Technique).

Aortic coarctation presents in adult life in a significant number of patients. The preferred treatment in this age group is percutaneous stent implantation without which life expectancy is reduced due to the complications of uncontrolled hypertension. We present the first case of an "uncrossable" aortic coarctation transversed using the BEACON (Brief Electrification of a guidewire to assist in crossing an Aortic CoarctatiON) technique, a novel approach incorporating the electrification of a guidewire. It requires standard transcaval equipment and techniques but crosses from aortic lumen-to-lumen instead of cava-to-aorta, thus creating a rail for successful stent delivery.

Temporal Changes in Coronary Hyperemic and Resting Hemodynamic Indices in Nonculprit Vessels of Patients With ST-Segment Elevation Myocardial Infarction.

Importance: Percutaneous coronary intervention (PCI) of nonculprit vessels among patients with ST-segment elevation myocardial infarction (STEMI) is associated with improved clinical outcome compared with culprit vessel-only PCI. Fractional flow reserve (FFR) and coronary flow reserve are hyperemic indices used to guide revascularization. Recently, instantaneous wave-free ratio was introduced as a nonhyperemic alternative to FFR. Whether these indices can be used in the acute setting of STEMI continues to be investigated. Objective: To assess the value of hemodynamic indices in nonculprit vessels of patients with STEMI from the index event to 1-month follow-up. Design, Setting, and Participants: This substudy of the Reducing Micro Vascular Dysfunction in Revascularized STEMI Patients by Off-target Properties of Ticagrelor (REDUCE-MVI) randomized clinical trial enrolled 98 patients with STEMI who had an angiographic intermediate stenosis in at least 1 nonculprit vessel. Patient enrollment was between May 1, 2015, and September 19, 2017. After successful primary PCI, nonculprit intracoronary hemodynamic measurements were performed and repeated at 1-month follow-up. Cardiac magnetic resonance imaging was performed from 2 to 7 days and 1 month after primary PCI. Main Outcomes and Measures: The value of nonculprit instantaneous wave-free ratio, FFR, coronary flow reserve, hyperemic index of microcirculatory resistance, and resting microcirculatory resistance from the index event to 1-month follow-up. Results: Of 73 patients with STEMI included in the final analysis, 59 (80.8%) were male, with a mean (SD) age of 60.8 (9.9) years. Instantaneous wave-free ratio (SD) did not change significantly (0.93 [0.07] vs 0.94 [0.06]; P = .12) and there was no change in resting distal pressure/aortic pressure (mean [SD], 0.94 [0.06] vs 0.95 [0.06]; P = .25) from the acute moment to 1-month follow-up. The FFR decreased (mean [SD], 0.88 [0.07] vs 0.86 [0.09]; P = .001) whereas coronary flow reserve increased (mean [SD], 2.9 [1.4] vs 4.1 [2.2]; P < .001). Hyperemic index of microcirculatory resistance decreased and resting microcirculatory resistance increased from the acute moment to follow-up. The decrease in distal pressure from rest to hyperemia was smaller at the acute moment vs follow-up (mean [SD], 10.6 [11.2] mm Hg vs 14.1 [14.2] mm Hg; P = .05). This blunted acute hyperemic response correlated with final infarct size (ρ, -0.29; P = .02). The resistive reserve ratio was lower at the acute moment vs follow-up (mean [SD], 3.4 [1.7] vs 5.0 [2.7]; P < .001). Conclusions and Relevance: In the acute setting of STEMI, nonculprit coronary flow reserve was reduced and FFR was augmented, whereas instantaneous wave-free ratio was not altered. These results may be explained by an increased hyperemic microvascular resistance and a blunted adenosine responsiveness at the acute moment that was associated with infarct size.

Pulse wave velocity can be accurately measured during transcatheter aortic valve implantation and used for post-procedure risk stratification.

OBJECTIVES: Mortality following TAVI remains notable and optimizing other features of cardiovascular health following this intervention can be overlooked. Aortic pulse wave velocity (PWV) is the gold-standard for measuring arterial stiffness and is a powerful predictor of mortality. We identified the potential to calculate PWV during TAVI and aimed to use this tool to assess long-term outcome. METHODS: Data from 186 patients who underwent TAVI between April 2016 and June 2017 was assessed. Invasive pressure data was simultaneously recorded from the femoral head and aortic root prior to TAVI and wave-time calculated using an automated foot-to-foot methodology. Distance was measured from the pre-TAVI CT. PWV was calculated from these values. RESULTS: Median PWV was 9.92 (95% CI 9.6-10.2) m/s. Multivariate analysis revealed a relationship with PWV and age (ß = 0.13, 95% CI 0.08-0.17, P < 0.01) and mean arterial pressure (ß = 0.04, 95% CI 0.02-0.06, P < 0.01). An optimum cut-off of 11.01m/s was calculated using a series of ROC curves against 1-year mortality (sensitivity = 0.64, specificity = 0.70, AUC = 0.67). Using this value, PWV was the only predictor of 1-year mortality on multivariate analysis (OR 3.57, 95% CI 1.36-9.42, P = 0.01) and stratified survival (log-rank P = 0.04). CONCLUSION: We have demonstrated that aortic PWV can be conveniently and accurately measured during TAVI. It is a strong predictor of post-procedure mortality and could be used to guide further therapy. This has particular relevance as TAVI moves into younger patients.

Diastolic-systolic velocity ratio to detect coronary stenoses under physiological resting conditions: a mechanistic study.

Objective: Diastolic-systolic velocity ratio (DSVR) is a resting index to assess stenoses in the left anterior descending artery (LAD). DSVR can be measured by echocardiographic or intracoronary Doppler flow velocity. The objective of this cohort study was to elucidate the fundamental rationale underlying the decreased DSVR in coronary stenoses. Methods: In cohort 1, simultaneous measurements of intracoronary Doppler flow velocity and pressure were acquired in the LAD of 228 stable patients. Phasic stenosis resistance, microvascular resistance and total vascular resistance (defined as stenosis and microvascular resistance combined) were studied during physiological resting conditions. Stenoses were classified according to severity by strata of 0.10 fractional flow reserve (FFR) units. Results: DSVR was decreased in stenoses with lower FFR. Stenosis resistance was equal in systole and diastole for every FFR stratum. Microvascular resistance was consistently higher during systole than diastole. In lower FFR strata, stenosis resistance as a percentage of the total vascular resistance increases both during systole and diastole. The difference between the stenosis resistance as a percentage of total vascular resistance during systole and diastole increases for lower FFR strata, with an accompanying rise in diastolic-systolic resistance ratio. A significant inverse correlation was observed between DSVR and the diastolic-systolic resistance ratio (r=0.91, p<0.001). In cohort 2 (n=23), DSVR was measured both invasively and non-invasively by transthoracic echocardiography, yielding a good correlation (r=0.82, p<0.001). Conclusions: The rationale by which DSVR is decreased distal to coronary stenoses is dependent on a comparatively higher influence of the increased stenosis resistance on total vascular resistance during diastole than systole.

Comprehensive physiological evaluation of epicardial and microvascular coronary domains using vascular conductance and zero flow pressure.

AIMS: Assessment of the coronary circulation has been based largely on pressure ratios (epicardial) and resistance (micro-vessels). Simultaneous assessment of epicardial (CEPI) and microvascular conductance (CMICRO) provides an intuitive approach using the same units for both coronary domains and expressing the actual deliverability of blood. The aim of this study was to develop a novel integral method for assessing the functional severity of epicardial and microvascular disease. METHODS AND RESULTS: We performed intracoronary pressure and Doppler flow velocity measurements in 403 vessels in 261 patients with stable coronary artery disease. Hyperaemic mid-to-late diastolic pressure and flow velocity (PV) relationships were calculated. The slope of the aortic PV indicates the overall conductance and the slope of the distal PV relationship represents CMICRO. The intercept with the x-axis represents zero-flow pressure (Pzf). CEPI was derived from microvascular and overall conductance. Median CEPI was higher compared to CMICRO (4.2 [2.1-8.0] versus 1.3 [1.0-1.7] cm/s/mmHg, p<0.001). CMICRO was independent of stenosis severity (1.3 [1.0-1.7] in FFR ≤0.80 versus 1.4 [1.0-1.8] in FFR >0.8, p=0.797). ROC curves (using FFR and HSR concordant vessels as standard) demonstrated an excellent ability of CEPI to characterise significant stenoses (AUC 0.93). When CEPI

Effect of Aortic Valve Calcium Quantity on Outcome After Balloon Aortic Valvuloplasty for Severe Aortic Stenosis.

Balloon aortic valvuloplasty has a role in a select group of patients with severe aortic stenosis. Identifying those appropriate patients who will benefit most is key. Given previous evidence demonstrating that histologically the intervention involves a physical disrupting of the cusp's calcium we hypothesized that the quantity of calcium seen at CT will influence outcome. We examined our cohort of patients who had undergone balloon aortic valvuloplasty and CT-quantified aortic valve calcium (AVC) between July 2011 and April 2014. All patients underwent echocardiography pre- and post-procedure and for those patients managed medically, again at 6 months. A potential predictive AVC value for mortality was calculated using Youden's index. A total of 240 aortic valvuloplasties were performed in 206 patients (male = 124). Valvuloplasty caused a significant (pre 0.63 ± 0.21 vs post 0.77 ± 0.27 cm2, p <0.01, n = 240), but temporary (post 0.80 ± 0.27 vs 6 months: 0.64 ± 0.18 cm2, p <0.01, n = 88) increase in valve area. Those patients with a non-severe AVC (<1853.5 AU) had a larger increase in valve area after valvuloplasty compared with those with more calcium (0.10 [95% confidence interval {CI} 0.05 to 0.10] vs 0.15 [95%CI 0.10 to 0.22] cm2, p = 0.049). Multivariate analysis revealed severe AVC (Hazard ratio 2.79, 95% CI 1.18 to 6.63, p = 0.02) along with pulmonary artery pressure post-valvuloplasty (Hazard ratio 1.02, 95% CI 1.00 to 1.03, p = 0.03) to be predictive of survival. In conclusion, in patients with severe aortic stenosis the degree of AVC impacts on the success of valvuloplasty.

Regression of left ventricular hypertrophy provides an additive physiological benefit following treatment of aortic stenosis: Insights from serial coronary wave intensity analysis.

AIM: Severe aortic stenosis frequently involves the development of left ventricular hypertrophy (LVH) creating a dichotomous haemodynamic state within the coronary circulation. Whilst the increased force of ventricular contraction enhances its resultant relaxation and thus increases the distal diastolic coronary "suction" force, the presence of LVH has a potentially opposing effect on ventricular-coronary interplay. The aim of this study was to use non-invasive coronary wave intensity analysis (WIA) to separate and measure the sequential effects of outflow tract obstruction relief and then LVH regression following intervention for aortic stenosis. METHODS: Fifteen patients with unobstructed coronary arteries undergoing aortic valve intervention (11 surgical aortic valve replacement [SAVR], 4 TAVI) were successfully assessed before and after intervention, and at 6 and 12 months post-procedure. Coronary WIA was constructed from simultaneously acquired coronary flow from transthoracic echo and pressure from an oscillometric brachial cuff system. RESULTS: Immediately following intervention, a decline in the backward decompression wave (BDW) was noted (9.7 ± 5.7 vs 5.1 ± 3.6 × 103  W/m2 /s, P < 0.01). Over 12 months, LV mass index fell from 114 ± 19 to 82 ± 17 kg/m2 . Accompanying this, the BDW fraction increased to 32.8 ± 7.2% at 6 months (P = 0.01 vs post-procedure) and 34.7 ± 6.7% at 12 months (P < 0.001 vs post-procedure). CONCLUSION: In aortic stenosis, both the outflow tract gradient and the presence of LVH impact significantly on coronary haemodynamics that cannot be appreciated by examining resting coronary flow rates alone. An immediate change in coronary wave intensity occurs following intervention with further effects appreciable with hypertrophy regression. The improvement in prognosis with treatment is likely to be attributable to both features.

Identification of capillary rarefaction using intracoronary wave intensity analysis with resultant prognostic implications for cardiac allograft patients.

Aims: Techniques for identifying specific microcirculatory structural changes are desirable. As such, capillary rarefaction constitutes one of the earliest changes of cardiac allograft vasculopathy (CAV) in cardiac allograft recipients, but its identification with coronary flow reserve (CFR) or intracoronary resistance measurements is hampered because of non-selective interrogation of the capillary bed. We therefore investigated the potential of wave intensity analysis (WIA) to assess capillary rarefaction and thereby predict CAV. Methods and results: Fifty-two allograft patients with unobstructed coronary arteries and normal left ventricular (LV) function were assessed. Adequate aortic pressure and left anterior descending artery flow measurements at rest and with intracoronary adenosine were obtained in 46 of which 2 were lost to follow-up. In a subgroup of 15 patients, simultaneous RV biopsies were obtained and analysed for capillary density. Patients were followed up with 1-3 yearly screening angiography. A significant relationship with capillary density was noted with CFR (r = 0.52, P = 0.048) and the backward decompression wave (BDW) (r = -0.65, P < 0.01). Over a mean follow-up of 9.3 ± 5.2 years patients with a smaller BDW had an increased risk of developing angiographic CAV (hazard ratio 2.89, 95% CI 1.12-7.39; P = 0.03). Additionally, the index BDW was lower in those who went on to have a clinical CAV-events (P = 0.04) as well as more severe disease (P = 0.01). Conclusions: Within cardiac transplant patients, WIA is able to quantify the earliest histological changes of CAV and can predict clinical and angiographic outcomes. This proof-of-concept for WIA also lends weight to its use in the assessment of other disease processes in which capillary rarefaction is involved.

Non-invasive coronary wave intensity analysis.

Wave intensity analysis is calculated from simultaneously acquired measures of pressure and flow. Its mathematical computation produces a profile that provides quantitative information on the energy exchange driving blood flow acceleration and deceleration. Within the coronary circulation it has proven most useful in describing the wave that originates from the myocardium and that is responsible for driving the majority of coronary flow, labelled the backward decompression wave. Whilst this wave has demonstrated valuable insights into the pathogenic processes of a number of disease states, its measurement is hampered by its invasive necessity. However, recent work has used transthoracic echocardiography and an established measures of central aortic pressure to produce coronary flow velocity and pressure waveforms respectively. This has allowed a non-invasive measure of coronary wave intensity analysis, and in particular the backward decompression wave, to be calculated. It is anticipated that this will allow this tool to become more applicable and widespread, ultimately moving it from the research to the clinical domain.

Estimation of coronary wave intensity analysis using noninvasive techniques and its application to exercise physiology.

Wave intensity analysis (WIA) has found particular applicability in the coronary circulation where it can quantify traveling waves that accelerate and decelerate blood flow. The most important wave for the regulation of flow is the backward-traveling decompression wave (BDW). Coronary WIA has hitherto always been calculated from invasive measures of pressure and flow. However, recently it has become feasible to obtain estimates of these waveforms noninvasively. In this study we set out to assess the agreement between invasive and noninvasive coronary WIA at rest and measure the effect of exercise. Twenty-two patients (mean age 60) with unobstructed coronaries underwent invasive WIA in the left anterior descending artery (LAD). Immediately afterwards, noninvasive LAD flow and pressure were recorded and WIA calculated from pulsed-wave Doppler coronary flow velocity and central blood pressure waveforms measured using a cuff-based technique. Nine of these patients underwent noninvasive coronary WIA assessment during exercise. A pattern of six waves were observed in both modalities. The BDW was similar between invasive and noninvasive measures [peak: 14.9 ± 7.8 vs. -13.8 ± 7.1 × 10(4) W·m(-2)·s(-2), concordance correlation coefficient (CCC): 0.73, P < 0.01; cumulative: -64.4 ± 32.8 vs. -59.4 ± 34.2 × 10(2) W·m(-2)·s(-1), CCC: 0.66, P < 0.01], but smaller waves were underestimated noninvasively. Increased left ventricular mass correlated with a decreased noninvasive BDW fraction (r = -0.48, P = 0.02). Exercise increased the BDW: at maximum exercise peak BDW was -47.0 ± 29.5 × 10(4) W·m(-2)·s(-2) (P < 0.01 vs. rest) and cumulative BDW -19.2 ± 12.6 × 10(3) W·m(-2)·s(-1) (P < 0.01 vs. rest). The BDW can be measured noninvasively with acceptable reliably potentially simplifying assessments and increasing the applicability of coronary WIA.

Evaluation of Microvascular Disease and Clinical Outcomes.

Although coronary microcirculatory dysfunction occurs in numerous cardiac conditions and influences prognosis, it has been largely ignored in clinical practice due to the lack of adequate methods for its assessment. Microcirculatory dysfuntion may result from a variety of causes, including structural remodelling (arterioles or capillaries), dysregulation (paradoxical arteriolar vasoconstriction), hypersensitivity to vasoactive factors or adrenergic drive, and extravascular compression of collapsable elements. Thus, the selection of a method to interrogate coronary microcirculation should be based on the suspected cause of dysfunction. This article reviews such assessment tools and their prognostic information.

Myocardial ischemia in aortic stenosis: insights from arterial pulse-wave dynamics after percutaneous aortic valve replacement.

Wave-intensity analysis is a technique that can qualify both the direction and magnitude of the forces accelerating and decelerating coronary blood flow and is derived from simultaneously acquired measures of coronary pressure and velocity using invasive intracoronary wires. Using this technique during TAVI, the dominant force (or 'wave') acting to increase the coronary blood flow which originates from microvascular relaxation is shown to be elevated in severe aortic stenosis and decreased post-implantation. Additionally, with increasing heart rate a progressive fall in the magnitude of this wave is noted and after TAVI this effect is reversed (returning towards the physiological norm). The potential causes of myocardial ischemia in aortic stenosis are clearly multi-factorial but this observation suggests a decoupling between the aorta and myocardium in aortic stenosis, the effects of which are magnified during increased heart rate.