Additive Prognostic Value of Coronary Flow Reserve in Patients With Chest Pain Syndrome and Normal or Near-Normal Coronary Arteries

In patients with angiographically normal coronary arteries and chest pain, pharmacologic stress echocardiography can identify a subgroup of patients with a less benign prognosis. Coronary flow reserve (CFR) in the left anterior descending artery (LAD) can currently be combined with wall motion analysis during vasodilator stress echocardiography. The aim of this study was to assess the prognostic value of CFR response in patients with normal coronary arteries and normal wall motion during stress. We selected 394 patients (171 men, 61 11 years of age) who underwent dipyridamole stress echocardiography (0.84 mg/kg over 6 minutes) with 2-dimensional echocardiography and CFR evaluation of the LAD by Doppler. All had angiographically nonsignificant (<50% quantitatively assessed) stenosis in any major vessel, normal left ventricular function (wall motion score index 1), and test negativity for conventional wall motion criteria. Images were independently read by a core laboratory for wall motion and a core laboratory for CFR. Mean CFR was 2.5 0.6 and 87 patients (22%) had an abnormal CFR <2. During a median follow-up of 51 months, 31 events occurred, namely 4 deaths and 27 nonfatal myocardial infarctions (3 ST-elevated myocardial infarctions and 24 non-ST-elevated myocardial infarctions). Kaplan-Meier survival estimates for hard events showed a better outcome for those patients with a normal CFR compared with those with an abnormal CFR (96% vs 55%, p 0.001, at 48 months of follow-up). In conclusion, in patients with angiographically normal or near-normal coronary arteries and preserved at-rest regional and global left ventricular function at baseline and during stress, CFR adds incremental value to the prognostic stratification achieved with clinical and angiographic data

Prognostic Correlates of Combined Coronary Flow Reserve Assessment on Left Anterior Descending and Right Coronary Artery in Patients with Negative Stress Echocardiography by Wall Motion Criteria.

Aims: To assess the prognostic correlates of Doppler echocardiographically derived coronary flow reserve (CFR) on two coronaries in patients with negative stress echo. Vasodilator stress echocardiography allows dual imaging of regional wall motion and CFR both on left anterior descending (LAD) and right coronary artery (RCA). Methods: The study group comprised 460 patients with known or suspected coronary artery disease and negative stress echo by wall motion criteria. All underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) stress echo with CFR evaluation of either LAD or RCA by Doppler, and were followed up for a median of 32 months. A CFR value of(2.0 was taken as abnormal. Results: CFR was abnormal in 174 patients (38%) (57 in LAD only, 48 in RCA only, and 69 in both LAD and RCA) and normal in 286 patients (62%). During follow-up, there were 77 cardiac events: 5 deaths, 44 acute coronary syndromes (6 STEMI, and 38 NSTEMI) and 28 late (.6 months from stress echo) revascularisations. CFR of (2.0 on LAD was the strongest multivariable predictor of either definite (death, acute coronary syndrome) and major (death, acute coronary syndrome, late revascularisation) events, followed by diabetes mellitus. Antiischaemic therapy at the time of testing and resting wall motion abnormality were also independently associated with major events. Preserved CFR in both LAD and RCA was associated with better (p,0.0001) definite and major event-free survival compared to abnormal CFR in one or both coronary vessels. Conclusion: CFR evaluation of either LAD or RCA allows the identification of distinct prognostic patterns. In particular, preserved CFR in both coronary vessels is highly predictive of a very favourable outcome, while reduced CFR in either coronary vessel, and especially on LAD, is a strong predictor of future cardiac events

Stress echocardiography for risk stratification of patients following coronary bypass surgery

Objectives: To assess the prognostic value of stress echocardiography following coronary bypass surgery. Methods: We evaluated 451 patients (360 men; age 65?10 years) who underwent stress echocardiography with exercise (n=33), dipyridamole (n=319) or dobutamine (n=99) after a median of 69 months from coronary bypass surgery. Patients were followed-up for the occurence of hard (death, infarction) and major events (death, infarction, late [>3 months] revascularization). Results: Ischemia at stress echo was assessed in 185 (41%) patients. During a median follow-up of 25 months, there were 119 events (56 deaths, 17 myocardial infarctions, and 46 late revascularizations). Additionally 55 patients underwent early [<3 months] revascularization and were censored. Independent predictors of hard events were age (HR=1.06; 95% CI=1.03-1.10; p<0.0001), and peak wall motion score index (HR=3.36; 95% CI=1.85-6.11; p<0.0001). 4-year major event rate was 26% in patients with and 17% in those without ischemia (p=0.44) (Figure). Independent predictors of major events were age (HR=1.03; 95% CI=1,01-1.06; p=0.002), ischemia at stress echo (HR=1.73; 95% CI=1.20-2.49; p=0.004), and resting wall motion score index (HR=1.82; 95% CI=1.20-2.77; p=0.005). 4-year major event rate was 40% in patients with and 26% in those without ischemia (p=0.02) (Figure). Conclusion: In patients with previous coronary bypass surgery, ischemia at stress echo is a multivariable indicator of future major events. However, it is unable to predict hard events

Ventricular-Arterial coupling during dipyridamole stress

Background: The interaction of the heart with the systemic vasculature, termed ventricular-arterial coupling, is a central determinant of net cardiovascular performance in normal and pathological conditions. Ventricular and arterial elastance can be easily assessed by echocardiography, both at rest and during stress. Aim: To assess noninvasively left ventricular-arterial coupling in healthy and diseased subjects at rest and during dipyridamole (DIP) stress. Materials and methods: We enrolled 365 patients (63?16 years; 231 males) referred to stress echo lab: 131 "normals" (Nl); 86 patients with coronary artery disease, 68 with negative (CAD, SE -) and 18 with positive (CAD, SE+) stress echo; 148 with idiopathic dilated cardiomyopathy (DCM). In all, ventricular-arterial coupling was indexed by the ratio of ventricular force (Systolic Pressure/End-Systolic Volume index) to arterial elastance (EaI, ratio of end-systolic pressure by stroke volume). 2D echo (for ESV and stroke volume) and cuff sphygmomanometer (systolic pressure, multiplied x 0.90 to obtain end-systolic pressure) provided the raw measurements. Results: At rest, EaI was profoundly increased in DCM (6.3?4.4; p<.001 vs. all other groups: Nl=4?1.1; CAD, SE-=3.8?1; CAD SE+=4.2?1.3). DIP maximized ventricular-arterial coupling in normals. Residual vasodilatation and contractile reserve slightly increased cardiac efficiency in DCM and in CAD SE- pts. The CAD SE+ pts showed negative contractile reserve and the worse stress ventricular arterial coupling (see figure). Conclusions: Ventricular-arterial coupling was optimized by DIP in normals, and disrupted in CAD patients with stress induced ischemia. Effective arterial elastance is dramatically increased in DCM at rest and weakly responds to vasodilator stress

Coronary Flow Reserve During Dipyridamole Stress Echocardiography Predicts Mortality

ObjectivesThe goal of this study was to evaluate the ability of coronary flow reserve (CFR) over regional wall motion to predict mortality in patients with known or suspected coronary artery disease (CAD).BackgroundCFR evaluated using pulsed Doppler echocardiography testing on left anterior descending artery is the state-of-the-art method during vasodilatory stress echocardiography.MethodsIn a prospective, multicenter, observational study, we evaluated 4,313 patients (2,532 men; mean age 65 ± 11 years) with known (n = 1,547) or suspected (n = 2,766) CAD who underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress echocardiography with CFR evaluation of left coronary descending artery (LAD) by Doppler. Overall mortality was the only endpoint analyzed.ResultsStress echocardiography was positive for ischemia in 765 (18%) patients. Mean CFR was 2.35 ± 0.68. At individual patient analysis, 1,419 (33%) individuals had CFR ≤2. During a median follow-up of 19 months (1st quartile 8; 3rd quartile 36), 146 patients died. The 4-year mortality was markedly higher in subjects with CFR ≤2 than in those with CFR >2, both considering the group with ischemia (39% vs. 7%; p < 0.0001) and the group without ischemia at stress echocardiography (12% vs. 3%; p < 0.0001). At multivariable analysis, CFR on LAD ≤2 (hazard ratio [HR]: 3.31; 95% confidence interval [CI]: 2.29 to 4.78; p < 0.0001), ischemia at stress echocardiography (HR: 2.40, 95% CI: 1.65 to 3.48, p < 0.0001), left bundle branch block (HR: 2.26, 95% CI: 1.50 to 3.41; p < 0.0001), age (HR: 1.08, 95% CI: 1.06–1.10; p < 0.0001), resting wall motion score index (HR: 3.52, 95% CI: 2.38 to 5.21; p < 0.0001), male sex (HR: 1.74, 95% CI: 1.12 to 2.52; p = 0.003), and diabetes mellitus (HR: 1.47, 95% CI: 1.03 to 2.08; p = 0.03) were independent predictors of mortality.ConclusionsCFR on LAD is a strong and independent indicator of mortality, conferring additional prognostic value over wall motion analysis in patients with known or suspected CAD. A negative result on stress echocardiography with a normal CFR confers an annual risk of death <1% in both patient groups

Prognostic implication of coronary flow reserve in diabetic and nondiabetic patients with negative dipyridamole stress echo by wall motion criteria

Objectives: Aim of this prospective, multicenter, observational study was to assess the prognostic value of Doppler echocardiographic derived coronary flow reserve (CFR) in diabetic and nondiabetic patients with known or suspected coronary artery disease (CAD) and negative dipyridamole stress echo. Methods: The study group consisted of 1130 patients (207 diabetics) with known (n=418) or suspected (n=712) CAD and negative stress echo by wall motion criteria. All underwent dipyridamole (up to 0.84 mg/kg over 6\u27) echo with CFR evaluation of left anterior descending artery by Doppler. A value of CFR <2.0 was considered abnormal. Results: CFR was normal in 821 (63%) and abnormal in 309 (27%) patients. During a median follow-up of 16 months, 98 events (8 deaths, 24 STEMI, and 66 NSTEMI) occurred. In addition, 89 patients underwent revascularization and were censored. Multivariable prognostic indicators were abnormal CFR (HR=4.95; 95% CI=3.26-7.50; p<0.0001), antianginal therapy at the time of testing (HR=1.96; 95% CI=1.29-2.98; p=0.002), age (HR=1.02; 95% CI=1.00-1.04; p=0.02), and resting wall motion abnormalities (HR=1.50; 95% CI=1.00-2.25; p=0.05). The 36-month event rate was lower (p<0.0001) for either diabetics and nondiabetics with normal CFR as compard to diabetics and nondiabetics with abnormal CFR (Figure). Conclusion: CFR provides effective prognostic information in diabetic and nondiabetic patients with known or suspected CAD and negative dipyridamole stress echo. In particular, a reduced CFR is associated with worse outcome in both populations

Genetic stress echocardiography: role of A2a receptors polymorphism in modulating coronary flow reserve response in non-ischemic dilated cardiomyopathy

Background: Vasodilator stress imaging is based on coronary A2a receptor stimulation via endogenous adenosine (with dipyridamole administration), exogenous adenosine, or selective A2a receptor stimulation (with binodenoson).The recognized inter-individual variability in response to adenosine might be in part determined by genetic polymorphism in A2a adenosine receptors. Aim: to assess whether A2a receptor (263 C>T and 1976 C>T) polymorphism affects the coronary flow reserve (CFR) response in patients with non-ischemic dilated cardiomyopathy (DCM). Methods: we evaluated 44 DCM patients 34 males; age 62?9 years) by transthoracic dipyridamole (0.84 mg/kg) stress echocardiography. All patients had an ejection fraction <40% (mean 21.1?16.3%) and angiographically normal coronary arteries with NYHA class <3. CFR was assessed on left anterior descending coronary artery using Doppler as the ration of maximal peak vasodilation (dipyridamole) to rest diastolic flow velocity. All patients underwent peripheral blood sampling and A2a receptor genotyping with PCR and enzyme restriction analysis. Results: CFR was 2.1?0.6 (range=1.5-4). There was no correlation between CFR and 263 C>T variant of A2a gene. However, patients with 1976 TT genotype had significantly lower values from 1976 CC patients (p<0.05). The 7 patients omozygous for 1976 TT had an OR=8.8 (95% CI, 1-81, p=0.04) for abnormal CFR. Conclusion: In DCM patients 1976 C>T polymorphism of the adenosine A2A receptor gene may affect CFR response. In particular, the 1976-TT variant of A2a gene blunts the coronary vasodilatory response

Recruitment of aged donor heart with pharmacological stress echo. A case report

BACKGROUND: The heart transplant is a treatment of the heart failure, which is not responding to medications, and its efficiency is already proved: unfortunately, organ donation is a limiting step of this life-saving procedure. To counteract heart donor shortage, we should screen aged potential donor hearts for initial cardiomyopathy and functionally significant coronary artery disease. Donors with a history of cardiac disease are generally excluded. Coronary angiography is recommended for most male donors older than 45 years and female donors older than 50 years to evaluate coronary artery stenoses. A simpler way to screen aged potential donor hearts for initial cardiomyopathy and functionally significant coronary artery disease should be stress echocardiography. CASE REPORT: A marginal donor (A 57 year old woman meeting legal requirements for brain death) underwent a transesophageal (TE) Dipyridamole stress echo (6 minutes accelerated protocol) to rule out moderate or severe heart and coronary artery disease. Wall motion was normal at baseline and at peak stress (WMSI = 1 at baseline and peak stress, without signs of stress inducible ischemia). The pressure/volume ratio was 9.6 mmHg/ml/m(2 )at baseline, increasing to 14 mmHg/ml/m(2 )at peak stress, demonstrating absence of latent myocardial dysfunction. The marginal donor heart was transplanted to a recipient "marginal" for co-morbidity ( a 63 year old man with multiple myeloma and cardiac amyloidosis , chronic severe heart failure, NYHA class IV). Postoperative treatment and early immunosuppressant regimen were performed according to standard protocols. The transplanted heart was assessed normal for dimensions and ventricular function at transthoracic (TT) echocardiography on post-transplant day 7. Coronary artery disease was ruled out at coronary angiography one month after transplant; left ventriculography showed normal global and segmental LV function of the transplanted heart. CONCLUSION: For the first time stress echo was successfully used in the critical theater of screening potential donor hearts. This method is enormously more feasible, less expensive, and more environmentally sustainable than any possible alternative strategy based on stress scintigraphy perfusion imaging or coronary angiography. The selection of hearts "too good to die" on the basis of bedside resting and stress echo can be a critical way to solve the mismatch between donor need and supply

Second-opinion stress tele-echocardiography for the Adonhers (Aged donor heart rescue by stress echo) project

<p>Abstract</p> <p>Background</p> <p>To resolve the current shortage of donor hearts, we established the Adonhers protocol. An upward shift of the donor age cut-off limit (from the present 55 to 65 years) is acceptable if a stress echo screening on the candidate donor heart is normal. This study aimed to verify feasibility of a "second opinion" of digitally transferred images of stress echo results to minimize technical variability in selection of aged donor hearts for heart transplant.</p> <p>Methods</p> <p>The informatics infrastructure was created for a core lab reading with a second opinion from the Pisa stress echo lab. To test the system, simulation standard stress echo cineloops were sent digitally from 5 peripheral labs to the central core lab.</p> <p>Starting January 2009, real marginal donor stress echos were sent via internet to the central core echo lab, Pisa, for a second opinion before heart transplant.</p> <p>Results</p> <p>In the simulation protocol, 30 dipyridamole stress echocardiograms were sent from the five peripheral echo labs to the central core lab in Pisa. Both the echo images and reports were correctly uploaded in the web system and sent to the core echo lab; the second opinion evaluation was obtained in all cases (100% feasibility). In the transplant protocol, eight donor cases were sent to the Pisa core lab for the second opinion protocol, and six of them were transplanted in marginal recipients.</p> <p>Conclusions</p> <p>Second-Opinion Stress Tele-Echocardiography can effectively be performed in a network aimed to safely expand the heart donor pool for heart transplant.</p