Prognostic implication of Doppler echocardiographic derived coronary flow reserve in patients with left bundle branch block.

AIMS: Myocardial ischaemia during pharmacological stress echocardiography is a strong prognostic predictor in patients with a left bundle branch block (LBBB). However, the additive value of Doppler-derived coronary flow reserve (CFR) during pharmacological stress testing remains to be investigated in this subset of patients. METHODS AND RESULTS: The study group consisted of 324 LBBB patients (187 men; age 68 ± 10 years) with known (n = 74) or suspected (n = 250) coronary artery disease who had undergone dipyridamole (up to 0.84 mg/kg over 6') stress echocardiography with CFR assessment of left anterior descending (LAD) by Doppler. A value of CFR ≤ 2.0 was considered abnormal. The median duration of follow-up was 15 months (first to third quartile: 8-34 months). Of the 324 patients, 52 (16%) had ischaemia at stress echo by wall motion criteria, and 139 (43%) had a CFR ≤ 2. During follow-up, 51 (16%) events occurred: 37 deaths and 14 myocardial infarctions (MIs). Age (HR: 1.09, 95% CI: 1.04-1.15, P < 0.0001), resting wall motion score index (HR: 5.29, 95% CI: 2.36-11.89, P < 0.0001), smoking habit (HR: 4.38, 95% CI: 1.93-9.91, P < 0.0001), and CFR ≤ 2 (4.69, 95% CI: 1.96-11.19, P = 0.001) were independently correlated with mortality, while CFR ≤ 2 (HR: 3.91, 95% CI: 1.90-8.04, P < 0.0001), age (HR: 1.06, 95% CI: 1.02-1.10, P = 0.001), smoking habit (HR: 2.25, 95% CI: 1.18-4.30, P = 0.01), ischaemia at stress echo (HR: 2.30, 95% CI: 1.11-4.77, P = 0.02), and resting wall motion score index (HR: 2.17, 95% CI: 1.11-4.25, P = 0.02) were independently correlated with death or MI. Four-year mortality and 4-year hard event rate were markedly higher in patients with CFR ≤ 2 than in those with CFR >2 (49 vs. 6% and 56 vs. 8%, respectively; P < 0.0001 for both). A CFR of ≤ 2 was associated with a significantly higher annual hard event rate independently of age, sex, ejection fraction, history of coronary artery disease, diabetes, and hypertension. Moreover, it was correlated with an increased (P < 0.0001) yearly mortality and event rate in patients with non-ischaemic stress echo conducted on therapy. At incremental analysis, a CFR of ≤ 2 added prognostic value to clinical findings, resting wall motion score index, ongoing anti-ischaemic therapy, and ischaemia at stress echo when both death and death or MI were the clinical endpoints. CONCLUSIONS: Abnormal CFR on LAD is a strong and independent indicator of mortality and death or MI in patients with LBBB, and is associated with markedly increased risk also in the subset of patients with stress echo negative for ischaemia on therapy.

Transplant of stunned donor hearts rescued by pharmacological stress echocardiography: a "proof of concept" report.

BACKGROUND: Due to the shortage of donor hearts, the criteria for acceptance have been considerably expanded. Hearts with regional or global left ventricular dysfunction are excluded from donation, but stress echo might be useful to identify patients with reversible wall motion abnormalities, potentially eligible for donation. METHODS: Six marginal candidate donors (mean age, 40 ± 13 years; three men) were enrolled. Resting echocardiography showed in all subjects a LV ejection fraction ≥ 45% (mean 51 ± 5%), but multiple risk factors were present. All donors had either global or discrete wall motion abnormalities: Wall Motion Score Index (WMSI) rest = 1.33 ± 0.25. Stress echocardiography was performed with the dipyridamole high dose of 0.84 mg/kg given over 6 min. RESULTS: The stress echo results were abnormal in three donors (WMSI rest = 1.51 ± 0.19 vs peak = 1.41 ± 0.30). These hearts were excluded from donation and cardiac pathology verification was available in two cases of confirmed LV myocardial fibrosis and/or severe coronary stenosis. The remaining three hearts improved during stress (WMSI rest = 1.15 ± 0.13 vs peak = 1.04 ± 0.06) and were transplanted uneventfully. Recipients (three males, mean age 53 ± 4 years) underwent post-TX coronary angiography, IVUS and endomyocardial biopsies. No recipient had primary graft failure, and all showed normal coronary angiography and normal LV function (EF = 57 ± 6%; WMSI = 1 ± 0) at 1-month post-TX. The recipients were alive at 12-month median follow-up. CONCLUSIONS: Dipyridamole stress echo performed in brain-dead potential donors with LV resting global or discrete wall motion abnormalities identifies hearts with severe morphologic abnormalities excluded from donation (with fixed response during stress echo) from hearts eligible for donation, showing improvement in regional wall motion during stress (viability response) and normal function and coronary anatomy following transplantation.

The impact of aging and atherosclerotic risk factors on transthoracic coronary flow reserve in subjects with normal coronary angiography.

Age may affect coronary flow reserve (CFR) especially in subjects with atherosclerotic risk factors (ARFs). The aim of this prospective, multicenter, observational study was to determine the effects of aging on CFR in patients with normal epicardial coronary arteries and ARFs. Three-hundred-thirty-five subjects (mean age = 61 years) with at least one ARF but normal coronary angiography underwent high-dose dipyridamole stress-echo with Doppler evaluation of left anterior descending artery. CFR was calculated as the ratio between hyperemic and resting coronary diastolic peak velocities. Patients were divided in age quartiles. CFR was progressively reduced with aging (1st quartile: 3.01 ± 0.69, 4th quartile: 2.39 ± 0.49, p < 0.001). This was mainly due to a gradual increase of resting velocities (1st quartile = 26.3 ± 6.1 cm/s, 4th quartile = 30.2 ± 6.4 cm/s, p < 0.001) while the reduction of hyperemic velocities remained unaffected (1st quartile = 77.7 ± 18.9 cm/s, 4th quartile = 70.9 ± 18.4 cm/s, NS). When age quartiles and ARFs were entered into a regression model, third and fourth age quartile (p < 0.0005 and p < 0.0001 respectively), left ventricular mass index (p < 0.0001), diastolic blood pressure (p < 0.001), total cholesterol (p < 0.002), fasting blood glucose (p < 0.01) and male gender (p < 0.05) were independent determinants of CFR in the whole population. Aging reduces coronary flow reserve in patients with angiographically normal coronary arteries due to a gradual increase of resting coronary flow velocity. CFR is also affected by atherosclerotic risk factors and left ventricular hypertrophy.

Machine Learning Algorithms for Prediction of Survival by Stress Echocardiography in Chronic Coronary Syndromes.

Stress echocardiography (SE) is based on regional wall motion abnormalities and coronary flow velocity reserve (CFVR). Their independent prognostic capabilities could be better studied with a machine learning (ML) approach. The study aims to assess the SE outcome data by conducting an analysis with an ML approach. We included 6881 prospectively recruited and retrospectively analyzed patients with suspected (n = 4279) or known (n = 2602) coronary artery disease submitted to clinically driven dipyridamole SE. The outcome measure was all-cause death. A random forest survival model was implemented to model the survival function according to the patient's characteristics; 1002 patients recruited by a single, independent center formed the external validation cohort. During a median follow-up of 3.4 years (IQR 1.6−7.5), 814 (12%) patients died. The mortality risk was higher for patients aged >60 years, with a resting ejection fraction < 60%, resting WMSI, positive stress-rest WMSI scores, and CFVR < 3.The C-index performance was 0.79 in the internal and 0.81 in the external validation data set. Survival functions for individual patients were easily obtained with an open access web app. An ML approach can be fruitfully applied to outcome data obtained with SE. Survival showed a constantly increasing relationship with a CFVR < 3.0 and stress-rest wall motion score index > Since processing is largely automated, this approach can be easily scaled to larger and more comprehensive data sets to further refine stratification, guide therapy and be ultimately adopted as an open-source online decision tool.

[Heart recruiment of elderly donors by pharmacological echostress]. / Reclutamento di cuore di donatori "anziani" con ecostress farmacologico. Descrizione di un caso.

BACKGROUND: The heart transplant is a treatment of the heart failure, which is not responding to medications. To counteract heart donor shortage, we should screen aged potential donor hearts for initial cardiomyopathy and functionally significant coronary artery disease, in order to exclude donors with a history of cardiac disease. A simple way to evaluate this 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, without signs of stress inducible ischemia, and there was no 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). 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. CONCLUSION: For the first time stress echo was successfully used for the selection of hearts "too good to die", representing 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.

BACKGROUND: 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. METHODS: 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.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. RESULTS: 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. CONCLUSIONS: Second-Opinion Stress Tele-Echocardiography can effectively be performed in a network aimed to safely expand the heart donor pool for heart transplant.

The prognostic value of Doppler echocardiographic-derived coronary flow reserve is not affected by concomitant antiischemic therapy at the time of testing.

BACKGROUND: When wall motion abnormality is the diagnostic end point, concomitant antiischemic therapy heavily modulates the prognostic value of dipyridamole echocardiography test (DET). A negative test result is less benign, and a positive test result is more malignant if performed under therapy. Recently, coronary flow reserve (CFR) was added to wall motion in dual imaging DET. The aim of the study was to determine whether antianginal medications affect the prognostic value of Doppler echocardiographic-derived CFR in patients with known or suspected coronary artery disease undergoing DET. METHODS: In a prospective, multicenter, observational study, we evaluated 1,779 patients (1,072 males; 64 +/- 11 years) who underwent high-dose dipyridamole (0.84 mg/kg for 6 minutes) stress echo with CFR evaluation of left anterior descending (LAD) artery by Doppler. RESULTS: Seven hundred thirty-three (41%) patients were on antiischemic therapy at time of testing (nitrates and/or calcium antagonists and/or beta-blockers). Mean CFR was 2.3. +/- 0.6. At individual patient analysis, 1,141 patients had normal (CFR >2.0) and 638 had abnormal (CFR

The independent prognostic value of contractile and coronary flow reserve determined by dipyridamole stress echocardiography in patients with idiopathic dilated cardiomyopathy.

The aim of this study was to evaluate the prognostic value of Doppler echocardiographically derived coronary flow reserve (CFR) in assessing inotropic response in patients with idiopathic dilated cardiomyopathy (IDC). One hundred thirty-two patients with IDC (90 men; mean age 62 +/- 11 years) were evaluated by transthoracic dipyridamole (0.84 mg/kg in 10 minutes) stress echocardiography. All patients had ejection fractions <40% (mean 33 +/- 7%) and angiographically normal coronary arteries, with New York Heart Association class 0.25. All patients were followed for a median of 24 months. Mean CFR was 2.0 +/- 0.5. On individual patient analysis, 48 patients had normal CFR (>2), and 84 had abnormal CFR. The mean wall motion score index at rest was 2.0 +/- 0.33 and decreased to 1.8 +/- 0.4 at peak dipyridamole dose (p <0.000). Forty-two patients (32%) had inotropic reserve. During follow-up, 19 patients died, and 34 showed worsening of New York Heart Association class. The worst outcomes were observed in those patients with abnormal CFR and no inotropic reserve with high-dose dipyridamole. In a Cox model, mitral insufficiency (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.1 to 2.8), New York Heart Association class (HR 2.0, 95% CI 1.1 to 3.7), abnormal CFR (HR 2.8, 95% CI 1.0 to 8.5), wall motion score index at rest (HR 3.5, 95% CI 1.3 to 9.8), and the absence of inotropic reserve with high-dose dipyridamole (HR 2.3, 95% CI 1.06 to 5.1) were independent predictors of survival. In conclusion, in patients with IDC, CFR is often impaired. Reduced CFR and the absence of an inotropic response during vasodilator stress are additive in predicting a worse prognosis.

Prognostic value of coronary flow reserve in medically treated patients with left anterior descending coronary disease with stenosis 51% to 75% in diameter.

According to American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions 2005 guidelines on percutaneous intervention, intracoronary physiologic measurement in the assessment of effects of intermediate coronary stenoses in patients with anginal symptoms is a class IIa indication. This study assessed the additional prognostic value of Doppler echocardiographically derived coronary flow reserve (CFR) in patients with single-vessel disease and intermediate stenosis severity. We enrolled 86 patients (44 men; 66 +/- 10 years of age) with angiographically assessed single-vessel coronary artery disease of the left anterior descending coronary artery (LAD) with quantitatively assessed diameter stenosis severity 50% to 75%. All patients underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) stress echocardiography with wall motion analysis by 2-dimensional echocardiography and CFR evaluation of the affected artery by Doppler. All patients were followed up for a median of 14 months (first quartile 10, third quartile 18) after diagnostic coronary angiography (without percutaneous intervention for a clinically driven decision). Mean diameter stenosis of the LAD was 58 +/- 10%. Mean CFR of the LAD was 2.09 +/- 0.5. Regional wall motion abnormality at peak stress was present in 17 patients. During follow-up, 24 events occurred: 6 nonfatal ST-elevation myocardial infarctions and 18 non-ST-elevation myocardial infarctions. Thirty-month spontaneous event-free survival was higher in patients with normal CFR and lower in patients with decreased CFR (86% vs 30%, p = 0.0001). At Cox analysis, a CFR <2 (hazard ratio 24.2, 95% confidence interval 3.2 to 179.7, p = 0.002) was the only independent prognostic predictor of outcome. In conclusion, in medically treated patients with single-vessel disease of intermediate severity, decreased CFR is associated with a worse outcome.

Dual-Imaging Stress Echocardiography for Prognostic Assessment of High-Risk Asymptomatic Patients with Diabetes Mellitus.

BACKGROUND: In patients with diabetes, the utility of diagnostic screening cardiac tests in subjects without clinical coronary artery disease remains controversial. The aim of this study was to assess the prognostic meaning of dual-imaging stress echocardiography (conventional wall motion analysis and Doppler-derived coronary flow velocity reserve [CFVR] of the left anterior descending coronary artery) in high-risk asymptomatic individuals with diabetes. METHODS: This was a prospective analysis of 230 asymptomatic patients with diabetes (128 men; mean age, 66 ± 9 years) with no clinical evidence of coronary artery disease, no Q waves or deep negative waves on the electrocardiogram, and no wall motion abnormalities on resting echocardiography. Of these subjects, 147 (64%) had target organ damage and 83 (36%) had two or more associated cardiovascular risk factors. All patients underwent dipyridamole stress echocardiography with CFVR assessment of the left anterior descending coronary artery by transthoracic Doppler, and test results were entered into a database at the time of testing for a clinical and outcome follow-up (mean, 4.6 ± 2.7 years). RESULTS: Inducible ischemia and reduced CFVR (≤2) were detected in six and 52 patients, respectively. A total of 54 subjects (23%) had abnormal test results (ischemia or reduced CFVR). During follow-up, 39 major adverse cardiac events (MACEs) occurred: 22 hard events (18 deaths and four nonfatal myocardial infarctions) and 17 coronary revascularizations. The yearly incidence rates of hard events and MACEs in the entire study population were 2.1% and 3.6%, respectively. Abnormal test results were the only multivariate indicator of both hard events (hazard ratio, 3.69; 95% CI, 1.54-8.80) and MACEs (hazard ratio, 6.12; 95% CI, 3.22-11.62). CONCLUSIONS: Abnormal test results were obtained in one of four cases and were a strong and independent predictor of future hard events and MACEs.

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/m2 at baseline, increasing to 14 mmHg/ml/m2 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.

The additive prognostic value of restrictive pattern and dipyridamole-induced contractile reserve in idiopathic dilated cardiomyopathy.

BACKGROUND: Diastolic dysfunction and lack of contractile reserve are unfavorable prognostic predictors in patients with dilated cardiomyopathy (DCM). AIMS: This study aims to assess whether diastolic dysfunction and lack of dipyridamole-induced contractile reserve were additive predictors of poor outcome in patients with DCM. METHODS: A total of 116 patients with DCM and ejection fraction (EF<35%) were studied by dipyridamole echo (0.84 mg/kg over 10 min). At rest, a restrictive filling pattern was defined as: E/A ratio >2 and an E-wave deceleration time of <140 ms on transmitral flow velocity profile. RESULTS: Rest wall motion score index (WMSI) was 2.2+/-0.3 and decreased to 1.9+/-0.41 after dipyridamole (p<0.001). During follow-up (median 26.5 months), 22 cardiac deaths occurred. At multivariate analysis, dipyridamole-induced contractile reserve yielded significant incremental prognostic value (RR=0.275, p<0.006) over NYHA class (RR=1.971, p<0.03), angiotensin-converting enzyme inhibitor therapy (RR=0.173, p<0.001), and left ventricular end-diastolic diameter (RR=1.131, p<0.001). The worst prognostic combination was the presence of restrictive pattern at rest and the absence of contractile reserve (deltaWMSI<0.15). CONCLUSION: In patients with DCM, the ominous combination of restrictive transmitral flow pattern and lack of contractile reserve during dipyridamole stress predicts an unfavourable outcome.

Clinical and functional determinants of coronary flow reserve in non-ischemic dilated cardiomyopathy: an echocardiographic study.

Coronary flow reserve (CFR) is impaired in non-ischemic dilated cardiomyopathy (DCM). Mechanisms by which such impairment occurs are still unknown, but cofactors such as diastolic compressive force, left ventricular hypertrophy, and microvascular disease have been implied. In order to characterize the determinants of CFR in non-ischemic DCM, we evaluated 110 non-ischemic DCM patients (58 men; age=61+/-12 years) and 21 age- and gender-matched control patients (14 men; age=59+/-13 years) by transthoracic (n=88) or transesophageal (n=22) dipyridamole (0.84 mg/ kg in 10') stress echocardiography. All patients showed angiographically normal coronary arteries. Non-ischemic DCM patients had an ejection fraction <45% while control patients had normal left ventricular systolic function. CFR was assessed on LAD by pulsed Doppler as the ratio of maximal vasodilation (dipyridamole) to rest peak diastolic coronary flow velocity. Mean CFR value was 2.0+/-0.6 for DCM patients and 3.2+/-0.5 for controls (p<0.01). At individual non-ischemic DCM patient analysis, 46 patients had normal CFR> or =2 (Group 1) and 64 patients had abnormal CFR<2 (Group 2). On univariate analysis, CFR reduction correlated with NYHA functional class (r=-0.33, p=0.001), left ventricular ejection fraction ( r=0.23, p=0.02), end-systolic volume (r=-0.23, p=0.02), systolic pulmonary artery pressure (r=-0.42, p=0.0001), deceleration time (r=0.24, p=0.02). Logistic multiregression analysis showed that only NYHA functional class significantly and negatively correlated with CFR (odds ratio=0.9; 95% confidence intervals: 0.03-.35, p=0.0001). In patients with non-ischemic DCM, CFR is reduced but with substantial individual variability, only partially accounted for by level of systolic and diastolic dysfunction. The clinical functional class is the strongest predictor of CFR reduction in these patients, with lowest flow reserve found in more advanced NYHA class.

Prognostic value of Doppler echocardiographic-derived coronary flow velocity reserve of left anterior descending artery in octogenarians with stress echocardiography negative for wall motion criteria.

AIMS: Doppler-derived coronary flow velocity reserve (CFVR) of left anterior descending (LAD) artery is an effective tool to predict overall mortality. The aim was to investigate the capability of CFVR to predict outcome in an unselected cohort of patients older than 80 years having stress echo negative by wall motion criteria. METHODS AND RESULTS: The study group refers to 369 patients aged > 80 years (156 men; mean age 83 ± 2 years) who had undergone dipyridamole stress echocardiography with CFVR assessment of LAD artery of known (n = 144) or suspected (n = 225) coronary artery disease. Stress echocardiography was negative for wall motion criteria in all cases. Mean CFVR was 2.07 ± 0.53. During a median follow-up of 21 months, there were 62 major adverse cardiac events (MACEs; 45 deaths and 17 non-fatal myocardial infarctions). With a receiver operating characteristic analysis, a CFVR of ≤ 1.93 was the best cut-off for predicting mortality and MACE. At individual patient analysis, 152 (41%) subjects had a CFVR of < 1.93. Annual mortality was 9.8% in patients with CFVR <1.93 and 3.7% in those with CFVR > 1.93 (P = 0.001); an annual MACE rate was 14.8% in the former and 4.5% in the latter (P < 0.0001). Of 15 clinical and echocardiographic parameters analysed, CFVR ≤ 1.93 [hazard ratio (HR) = 2.17, 95% CI 1.14-4.10] and resting wall motion abnormality (RWMA; HR = 2.60; 95% CI 1.35-5.00) were multivariable indicators of mortality. Moreover, CFVR ≤ 1.93 (HR = 2.69, 95% CI 1.56-4.67), and RWMA (HR = 2.38; 95% CI 1.31-4.33) were also strong independent predictors of MACEs. At incremental analysis, CFR ≤ 1.93 added prognostic information over clinical evaluation and RWMA when both mortality and MACE were taken as clinical end points. CONCLUSIONS: A reduced CFVR of LAD artery is a strong and independent indicator of both mortality and MACE, adding prognostic information over clinical evaluation and RWMA. Conversely, a preserved CFVR predicts a favourable outcome particularly in subjects with no RWMA.

Prognostic meaning of coronary microvascular disease in type 2 diabetes mellitus: a transthoracic Doppler echocardiographic study.

BACKGROUND: The prognostic value of Doppler-derived coronary flow velocity reserve (CFVR) of the left anterior descending coronary artery in patients with type 2 diabetes with preserved left ventricular systolic function and without flow-limiting stenoses on angiography remains undetermined. METHODS: The study sample consisted of 144 patients with type 2 diabetes (82 men; mean age 62 ± 10 years) with chest pain or angina-equivalent symptoms, no histories of coronary artery disease, and echocardiographic ejection fractions ≥ 50%. All patients underwent dipyridamole stress echocardiography with CFVR assessment of the left anterior descending coronary artery by transthoracic Doppler echocardiography and coronary angiography showing normal coronary arteries or nonobstructive coronary artery disease. RESULTS: Mean CFVR was 2.44 ± 0.57. On individual patient analysis, 109 patients (76%) had CFVR > 2, and 35 (24%) had CFVR ≤ 2. During a median follow-up period of 29 months (interquartile range, 14-44 months), 17 hard events (five deaths, 12 nonfatal myocardial infarctions) occurred. The annual hard-event rate was 13.9% in subjects with CFVR ≤ 2 and 2.0% in those with CFVR > 2. The annual event rate associated with CFVR ≤ 2 was significantly higher both in patients with left ventricular hypertrophy (P < .0001) and in those without left ventricular hypertrophy (P = .048). On Cox analysis, CFVR ≤ 2 (hazard ratio, 11.20; 95% confidence interval, 3.07-40.92), and male sex (hazard ratio, 7.80; 95% confidence interval, 1.74-34.97) were independent prognostic indicators, whereas nonobstructive coronary artery disease was not an independent predictor of outcomes. CONCLUSIONS: Microvascular dysfunction before the occurrence of coronary artery involvement is a strong and independent predictor of outcomes in patients with type 2 diabetes. Vasodilator stress CFVR is a suitable tool to assess microvascular dysfunction in routine clinical practice.

Coronary flow reserve during dipyridamole stress echocardiography predicts mortality.

OBJECTIVES: The 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). BACKGROUND: CFR evaluated using pulsed Doppler echocardiography testing on left anterior descending artery is the state-of-the-art method during vasodilatory stress echocardiography. METHODS: In 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. RESULTS: Stress 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. CONCLUSIONS: CFR 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.

Diagnostic and prognostic value of Doppler echocardiographic coronary flow reserve in the left anterior descending artery in hypertensive and normotensive patients [corrected]..

BACKGROUND: Vasodilator stress echocardiography allows dual imaging of regional wall motion and coronary flow reserve (CFR) on left anterior descending (LAD) artery. Hypertension may affect CFR independently of obstructive coronary artery disease (CAD) through coronary microcirculatory damage. AIMS: The authors sought to determine the best value of Doppler-echocardiography-derived coronary flow reserve (CFR) for detecting ≥75% stenosis of the left anterior descending artery (LAD) and assessing the risk in patients with and without hypertension. Participants The study group was formed by 2089 patients (1411 hypertensive patients and 678 normotensive patients) with known or suspected coronary artery disease who underwent dipyridamole (up to 0.84 mg/kg over 6 min) stress echo with CFR assessment of LAD by Doppler and coronary angiography. RESULTS: Mean CFR was 2.20±0.62 in hypertensive patients and 2.36±0.70 in normotensive patients (p<0.0001). A significant LAD stenosis was present in 376 (18%) cases. With a receiver operating characteristic analysis, a CFR ≤1.91 was the best value for diagnosing LAD stenosis in both hypertensive patients (area under curve 0.86 (95% CI 0.84 to 0.88), sensitivity 87% (95% CI 82% to 91%), specificity 76% (95% CI 73% to 78%)) and normotensive patients (area under curve 0.90 (95% CI 0.88 to 0.92), sensitivity 89% (95% CI 81% to 95%), specificity 80% (95% CI 77% to 83%)). During a median follow-up of 15 months, there were 348 events (58 deaths, 79 ST elevation myocardial infarctions and 211 non-ST elevation myocardial infarctions). Multivariable prognostic indicators were age (HR=1.0; 95% CI 1.0 to 1.04), test positivity for wall motion criteria (HR=5.9; 95% CI 3.6 to 9.6) and CFR on LAD ≤1.91 (HR=3.4; CI 95% 2.0 to 5.6) in normotensive patients and previous myocardial infarction (HR=1.3; 95% CI 1.0 to 1.7), test positivity for wall motion criteria (HR=5.0; 95% CI 3.8 to 6.6) and CFR on LAD ≤1.91 (HR=3.1; CI 95% 2.4 to 4.1) in hypertensive patients. CONCLUSIONS: CFR on LAD provides useful information for vessel stenosis and prognostic assessment in both hypertensive and normotensive patients. However, diagnostic specificity is reduced in hypertensive.

Favorable short-term outcome of transplanted hearts selected from marginal donors by pharmacological stress echocardiography.

BACKGROUND: Because of the shortage of donor hearts, the criteria for acceptance have been considerably expanded. Abnormal results on pharmacologic stress echocardiography are associated with significant coronary artery disease and/or occult cardiomyopathy on verification by cardiac autopsy. The aim of this study was to establish the feasibility of an approach based on pharmacologic stress echocardiography as a gatekeeper for extended heart donor criteria. METHODS: From April 2005 to April 2010, 39 "marginal" candidate donors (mean age, 56 ± 6 years; 21 men) were initially enrolled. After legal declaration of brain death, marginal donors underwent rest echocardiography, and if the results were normal, dipyridamole (0.84 mg/kg over 6 min, n = 25) or dobutamine (up to 40 µg/kg/min, n = 3) stress echocardiography. RESULTS: A total of 19 eligible hearts were found with normal findings. Of these, three were not transplanted because of the lack of a matching recipient, and verification by cardiac autopsy showed absence of significant coronary artery disease or cardiomyopathy abnormalities. The remaining 16 eligible hearts were uneventfully transplanted in marginal emergency recipients. All showed normal (n = 14) or nearly normal (minor single-vessel disease in two) angiographic, intravascular ultrasound, hemodynamic and ventriculographic findings at 1 month. At follow-up (median, 14 months; interquartile range, 4-31 months), 14 patients survived and two had died, one at 2 months from general sepsis and one at 32 months from allograft vasculopathy in recurrent multiple myeloma. CONCLUSIONS: Pharmacologic stress echocardiography can safely be performed in candidate heart donors with brain death and shows potential for extending donor criteria in heart transplantation.

Implication of the continuous prognostic spectrum of Doppler echocardiographic derived coronary flow reserve on left anterior descending artery.

The additive prognostic value of coronary flow reserve (CFR) over regional wall motion has been established, but there is more than a binary (normal-abnormal) response in CFR, which can be continuously titrated. We assessed the prognostic value of quartiles of CFR, evaluated by transthoracic Doppler of the left anterior descending coronary artery (LAD), in patients with known or suspected coronary artery disease (CAD). One thousand six hundred twenty patients (1,006 men, 64 +/- 11 years of age) underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) stress echocardiography with CFR evaluation of LAD by Doppler and coronary angiography. Patients were followed up for a median of 19 months. Mean CFR in the entire population was 2.25 +/- 0.65. Stress echocardiogram was positive for ischemia in 480 patients (30%). Obstructive (>or=70% vessel stenosis) CAD at angiography was present in 650 patients (40%). During follow-up, there were 298 events (42 deaths, 73 ST-elevation myocardial infarctions, and 183 non-ST-elevation myocardial infarctions). Patients (n = 399) undergoing revascularization were censored. With the Kaplan-Meier method, the first quartile of CFR (

Prognostic effect of coronary flow reserve in women versus men with chest pain syndrome and normal dipyridamole stress echocardiography.

The aim of this study was to investigate the prognostic effect of coronary flow reserve (CFR) on left anterior descending artery (LAD) in women and men with chest pain of unknown origin and normal stress echocardiogram. The study population consisted of 1,660 patients (906 women, 754 men) with chest pain syndrome, no wall motion abnormality on echocardiogram at rest, and dipyridamole (up to 0.84 mg/kg over 6 minutes) stress echocardiogram negative for wall motion criteria. All had undergone stress echocardiography with combined evaluation of CFR on LAD by Doppler. A CFR value ≤2.0 was considered abnormal. Median duration of follow-up was 19 months (interquartile range 10 to 34). Abnormal CFR was assessed in 171 women (19%) and 147 men (19%, p = 0.80). During follow-up, 80 events (20 deaths, 13 ST-elevation myocardial infarctions, and 47 non-ST-elevation myocardial infarctions) occurred. In addition, 128 patients underwent revascularization and were censored. CFR ≤2.0 on LAD was independently associated with prognosis in women (hazard ratio [HR] 16.48, 95% confidence interval [CI] 7.17 to 37.85, p <0.0001) and in men (HR 6.23, 95% CI 3.42 to 11.33, p <0.0001). Antianginal therapy at time of testing (HR 2.11, 95% CI 1.14 to 3.90, p = 0.02) was also a multivariable prognostic predictor in men. Four-year event rate associated with CFR values ≤2.0 and >2.0 were, respectively, 27% and 2% in women (p <0.0001) and 42% and 8% in men (p <0.0001). In conclusion, decreased CFR on LAD is associated with markedly increased risk in women and men with chest pain syndrome and a normal result of dipyridamole stress echocardiography. Conversely, preserved CFR on LAD predicts excellent survival, particularly in women.