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.

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.

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.

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.

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.

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.

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.

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.

[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.

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.

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.

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.

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 (

Stress echocardiography as a gatekeeper to donation in aged marginal donor hearts: anatomic and pathologic correlations of abnormal stress echocardiography results.

BACKGROUND: Owing to the shortage of donor hearts, the criteria for acceptance have been considerably expanded. Pharmacologic stress echocardiography is highly accurate in identifying prognostically significant coronary artery disease, but brain death and catecholamine storm in potential heart donors may substantially alter the cardiovascular response to stress. This study assessed correlates of an abnormal resting/stress echocardiography results in potential donors. METHODS: From April 2005 to December 2007, 18 marginal candidate donors (9 men) aged 58 +/- 5 years were initially enrolled. After legal declaration of brain death, all marginal donors underwent bedside echocardiography, with baseline and (when resting echocardiography was normal) dipyridamole (0.84 mg/kg in 6 min) or dobutamine (up to 40 microg/kg/min) stress echo. Non-eligible hearts (with abnormal rest or stress echo findings) were excluded and underwent cardioautoptic verification. RESULTS: Resting echocardiography showed wall motion abnormalities in 5 patients (excluded from donation). Stress echocardiography was performed in the remaining 13 (dipyridamole in 11; dobutamine in 2). Results were normal in 7, of which 6 were uneventfully transplanted in marginal recipients. Results were abnormal in 6, and autoptic verification performed showed coronary artery disease in 5, and initial cardiomyopathy in 1. CONCLUSIONS: Bedside pharmacologic stress echocardiography can safely be performed in candidate heart donors, is able to unmask occult coronary artery disease or cardiomyopathy, and shows potential to extend donor criteria in heart transplantation. Further experience with using marginal donors is needed before exact guidelines can be established.

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 implications of coronary flow reserve on left anterior descending coronary artery in hypertrophic cardiomyopathy.

The aim of the study was to prospectively evaluate a cohort of patients with hypertrophic cardiomyopathy (HC) after coronary flow reserve (CFR) assessment of the left anterior descending coronary artery. Sixty-eight patients with HC (40 men, mean +/- SD 58 +/- 12 years of age) underwent dipyridamole (up to 0.84 mg/kg over 6 minutes) echocardiography with CFR evaluation of the left anterior descending coronary artery by Doppler. Seventy-four age- and gender-matched, apparently healthy subjects served as controls. A CFR value <2.0 was considered abnormal. CFR was decreased in patients with HC versus controls (2.12 +/- 0.39 vs 2.78 +/- 0.58, p <0.0001). CFR was abnormal in 26 of 39 symptomatic and in 5 of 29 asymptomatic patients with HC (67% vs 17%, p <0.0001). In addition, patients with HC with left ventricular obstruction had decreased CFR (p <0.0001) compared with those without obstruction. During follow-up (22 +/- 13 months), 27 events occurred: 1 sudden death, 1 nonfatal myocardial infarction, 4 cardioverter-defibrillator implantations, 6 hospitalizations for heart failure, 5 unstable anginas, 2 syncopes, and 8 atrial fibrillations. Three-year event rate was markedly higher in patients with abnormal than in those with normal CFR (79% vs 17%, p <0.0001). Events were more frequent in symptomatic than in asymptomatic patients (62% vs 10%, p <0.0001). However, the latter had a 10-fold increased risk of events in the presence of abnormal CFR (40% vs 4%, p = 0.02). In conclusion, mean CFR is markedly lower in patients with HC than in apparently healthy subjects. Abnormal CFR is a strong and independent predictor of outcome in patients with HC.

Usefulness of stress echocardiography for risk stratification of patients after percutaneous coronary intervention.

The prognostic value of stress echocardiography in patients with previous percutaneous coronary intervention (PCI) remains undefined. The aim of this study was to investigate the prognostic implication of stress echocardiography after PCI. The study group comprised 1,063 patients (794 men, 65 +/- 10 years of age) who underwent stress echocardiography with exercise (n = 105), dipyridamole (n = 780), or dobutamine (n = 178) after a median of 10 months from a successful PCI. Of these patients, 616 (58%) complained of chest pain and 447 (42%) were asymptomatic. Stress echocardiogram was positive for inducible ischemia in 328 patients (31%). During a median follow-up of 20 months, there were 167 events (61 deaths, 106 infarctions). Independent predictors of mortality were age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03 to 1.09, p <0.0001), wall motion score index at rest (HR 3.91, 95% CI 2.19 to 6.99, p <0.0001), and ischemia at stress echocardiography (HR 1.82, 95% CI 1.05 to 3.16, p = 0.03). Five-year mortalities were 20% in patients with and 9% in those without ischemia (p = 0.006). Independent predictors of hard events were ischemia at stress echocardiography (HR 3.82, 95% CI 2.75 to 5.29, p <0.0001), age (HR 1.02, 95% CI 1.01 to 1.04, p = 0.009), wall motion score index at rest (HR 1.98, 95% CI 1.30 to 3.02, p = 0.002), multivessel disease at time of PCI (HR 1.45, 95% CI 1.05 to 2.02, p = 0.02), and female gender (HR 1.44, 95% CI 1.03 to 2.01, p = 0.03). Five-year hard event rates were 53% in patients with and 16% in those without ischemia (p <0.0001). Stress echocardiographic positivity added prognostic information to clinical and at-rest echocardiographic parameters in symptomatic and asymptomatic patients. Moreover, it identified a subset of patients at higher risk of developing hard events independent of the subtending coronary anatomy (multivessel or single vessel disease). In conclusion, stress echocardiography is effective in risk-stratifying patients with previous PCI. In particular, inducible ischemia is a strong and independent predictor of mortality and hard events.

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