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.

Reduced coronary flow velocity reserve and blunted heart rate reserve identify a higher risk group in patients with chest pain and negative emergency department evaluation.

To estimate the prognostic value of stress echo (SE) with the assessment of coronary flow velocity reserve (CFVR) and heart rate reserve (HRR) in patients admitted for chest pain with non-diagnostic EKG, negative troponin, and without inducible regional wall motion abnormalities (RWMA). 658 patients (age 67 ± 12 years) admitted to our Emergency Department with chest pain, non-diagnostic EKG, and negative serial troponin underwent dipyridamole (0.84 mg/kg in 6') SE with simultaneous assessment of RWMA, CFVR in the left anterior descending artery, and HRR as peak/rest heart rate. The outcome measure was all-cause mortality. Of the 658 patients initially enrolled, 20 (3%) showed RWMA during SE and were referred to ischemia-driven revascularization. In the remaining 638, CFVR was abnormal (≤ 2.0) in 148 patients (23%). HRR was abnormal (≤ 1.22 in patients in sinus rhythm, or ≤ 1.17 in patients with permanent atrial fibrillation) in 196 patients (31%). During a follow-up of 7.3 ± 4.3 years, 151 (24%) patients died. Survival at 8 years was 93% in patients with normal CFVR and HRR, 76% in patients with abnormal CFVR only, 73% in patients with abnormal HRR only, and 38% in those with abnormal CFVR and HRR (p < 0.0001). At multivariable analysis, abnormal CFVR (HR 1.49, 95% CI 1.05-2.10, p = 0.02) and abnormal HRR (HR 2.01, 95% CI 1.43-2.84, p < 0.0001) were independent predictors of survival. In admitted patients with non-ischemic EKG, negative serial troponin, and without RWMA during dipyridamole SE, a reduced CFVR and blunted HRR independently identify a subset with worse survival in the long term. Upper panel: Color and pulsed-wave Doppler with the electrocardiographic lead tracing of Four different response patterns (from left to right): normal CFVR and HRR; normal CFVR, abnormal HRR; abnormal CFVR, normal HRR; abnormal CFVR and HRR. Lower panel: The annualized death rate for each of the four groups with negative SE for RWMA and stratified according to the presence of CFVR and HRR: none, one, or two abnormalities.

[A rare case of myocarditis and pulmonary embolism after BNT162b2 mRNA vaccine]. / Raro caso di miocardite ed embolia polmonare dopo vaccino a mRNA BNT162b2.

In the clinical research arsenal, the COVID-19 vaccines are the strongest weapons against the most important worldwide sanitary crisis of the last centuries. Even if vaccine adverse events have mild clinical relevance, several thromboembolic events occurring after adenoviral recombinant vaccine administration have been reported. Cases of myocarditis and pericarditis after administration of mRNA vaccines have also recently been described. We report the case of a patient who suffered from two rare adverse events after BNT162b2 mRNA vaccine administration (Pfizer-BioNTech): acute myocarditis and pulmonary embolism. Although the temporal consequentiality does not demonstrate a causal link, the strong analogies emerging in the latest clinical reports suggest a possible relation. Further studies are needed to understand the potential mechanisms of myocardial damage and atypical thrombosis. Despite the favorable and self-limiting clinical course of post-vaccinal myocarditis, in these cases a tight follow-up is advisable and vaccine adverse event reporting remains mandatory, especially if not described during pivotal clinical trials.

Additional prognostic value of heart rate reserve over left ventricular contractile reserve and coronary flow velocity reserve in diabetic patients with negative vasodilator stress echocardiography by regional wall motion criteria.

AIMS: In diabetic patients, a blunted left ventricular contractile reserve (LVCR) and/or a reduced coronary flow velocity reserve (CFVR) identify patients at higher risk in spite of stress echocardiography (SE) negative for ischaemia. Cardiac autonomic dysfunction contributes to risk profile independently of inducible ischaemia and can be assessed with heart rate reserve (HRR). We sought to assess the added prognostic value of HRR to LVCR and CFVR in diabetic patients with non-ischaemic SE. METHODS AND RESULTS: Six-hundred and thirty-six diabetic patients (age 68 ± 9 years, 396 men, ejection fraction 58 ± 10%) with sinus rhythm on resting electrocardiogram underwent dipyridamole SE in a two-centre prospective study with assessment of wall motion, force-based LVCR (stress/rest ratio, normal value > 1.1), CFVR of the left anterior descending coronary artery (stress/rest ratio, normal value >2.0), and HRR (stress/rest ratio, normal value >1.22). All-cause death was the only considered endpoint. During a median follow-up of 39 months, 94 (15%) patients died. Independent predictors of death were abnormal CFVR [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.0-2.52, P = 0.05], reduced LVCR (HR 1.76, 95% CI 1.15-2.69, P = 0.009), and blunted HRR (HR 1.92, 95% CI 1.24-2.96, P = 0.003). Eight-year death rate was 9% for patients with triple negativity (n = 252; 40%), 18% for those with single positivity (n = 216; 34%), 36% with double positivity (n = 124; 19%), and 64% for triple positivity (n = 44; 7%) (P < 0.0001). CONCLUSION: Diabetic patients with dipyridamole SE negative for ischaemia still may have a significant risk in presence of an abnormal LVCR and/or CFVR and/or HRR, which assess the underlying myocardial, microvascular, and cardiac autonomic dysfunction. CLINICAL TRIALS: Gov Identifier NCT 030.49995.

Prognostic Value of Heart Rate Reserve during Dipyridamole Stress Echocardiography in Patients With Abnormal Chronotropic Response to Exercise.

Heart rate reserve (HRR) during physical or pharmacological stress is a sign of cardiac autonomic function and sympathetic reserve, but it can be reduced during exercise for confounders such as poor motivation, drugs or physical fitness. In this study we sought to assess the prognostic meaning of HRR during dipyridamole stress echocardiography (DSE) in patients with abnormal chronotropic response to exercise. From 2004 to 2019, we prospectively acquired and retrospectively analyzed 379 patients (age 62 ± 11 years; ejection fraction 60 ± 5%) with suspected (n = 243) or known (n = 136) chronic coronary syndromes, referred to DSE for chronotropic incompetence during upright bicycle exercise-electrocardiography test defined as HRR used [(peak HR - rest HR) / (220 - age) - rest HR] ≤80% in patients off and ≤62% in patients on beta-blockers. All patients were in sinus rhythm and underwent DSE (0.84 mg/kg) within 3 months of exercise testing. During DSE, age-independent HRR (peak/rest HR) ≤1.22 was considered abnormal. All patients were followed-up. All-cause death was the only outcome measure. HRR during DSE was normal in 275 (73%) and abnormal in 104 patients (27%). During a follow-up of 9.0 ± 4.2 years, 67 patients (18%) died. The 15-year mortality rate was 23% in patients with normal and 61% in patients with abnormal HRR (p < 0.0001). At multivariable analysis a blunted HRR during DSE was an independent predictor of outcome (hazard ratio 2.01, 95% confidence intervals 1.23-3.29; p = 0.005) with age and diabetes, while neither inducible ischemia nor ongoing beta-blocker therapy were significant predictors. In conclusion, a blunted HRR during DSE predicts a worse survival in patients with chronotropic incompetence during exercise test. HRR during DSE is an appealingly simple biomarker of cardiac autonomic dysfunction independent of imaging, exercise and beta-blocker therapy.

Reduced Sympathetic Reserve Detectable by Heart Rate Response after Dipyridamole in Anginal Patients with Normal Coronary Arteries.

Background. Patients with ischemia and normal coronary arteries (INOCA) may show abnormal cardiac sympathetic function, which could be unmasked as a reduced heart rate reserve (HRR) during dipyridamole stress echocardiography (SE). Objectives. To assess whether HRR during dipyridamole SE predicts outcome. Methods. Dipyridamole SE was performed in 292 patients with INOCA. HRR was measured as peak/rest heart rate and considered abnormal when ≤1.22 (≤1.17 in presence of permanent atrial fibrillation). All-cause death was the only endpoint. Results. HRR during SE was normal in 183 (63%) and abnormal in 109 patients (37%). During a follow-up of 10.4 ± 5.5 years, 89 patients (30%) died. The 15-year mortality rate was 27% in patients with normal and 54% in those with abnormal HRR (p < 0.0001). In a multivariable analysis, a blunted HRR during SE was an independent predictor of outcome (hazard ratio 1.86, 95% confidence intervals 1.20-2.88; p = 0.006) outperforming inducible ischemia. Conclusions. A blunted HRR during dipyridamole SE predicts a worse survival in INOCA patients, independent of inducible ischemia.

The obesity paradox in the stress echo lab: fat is better for hearts with ischemia or coronary microvascular dysfunction.

BACKGROUND: Obesity is an independent risk factor for coronary artery disease (CAD), but once CAD has developed it has been associated with improved survival ("obesity paradox"). AIM: To assess how obesity affects prognosis in patients with or without inducible ischemic regional wall motion abnormalities (RWMA) and/or abnormal coronary flow velocity reserve (CFVR) during stress echocardiography (SE). METHODS: In an observational retrospective two- center study design, we analyzed 3249 consecutive patients (1907 men; age 66 ± 12 years; body mass index, BMI, 26.9 ± 4.1 kg/m2) with known (n = 1306) or suspected (n = 1943) CAD who underwent dipyridamole SE with simultaneous evaluation of RWMA and CFVR. All-cause death was the outcome end-point. RESULTS: 1075 patients were lean (BMI 18.5-24.9 kg/m2), 1523 overweight (BMI 25.0-29.9 kg/m2), and 651 obese (≥30.0 kg/m2). Ischemic test result for RWMA occurred in 28 (3%) lean, 69 (4%) overweight, and 28 (4%) obese patients (p = 0.03). An abnormal CFVR (≤2.0) was found in 281 (26%) lean, 402 (26%) overweight and 170 (26%) obese patients (p = 0.99). During 68 ± 44 months of follow-up, 496 (15%) patients died. At multivariable Cox analysis, BMI ≥ 30 was an independent predictor of reduced mortality in the 878 patients with stress-induced (≥2 segments) RWMA and/or CFVR abnormality (HR 0.58, 95% CI 0.40-0.84; p = 0.003), while showed no effect at univariate analysis in the 2371 patients with no RWMA and normal CFVR (HR 1.04, 95% CI 0.74-1.46; p = 0.84). CONCLUSIONS: Obesity exerts a "paradoxical" protective effect in patients with stress-induced ischemia and/ or coronary microvascular dysfunction, and shows a neutral effect in patients with normal CFVR and no stress-induced RWMA.

Prognostic Value of Heart Rate Reserve in Patients with Permanent Atrial Fibrillation during Dipyridamole Stress Echocardiography.

In patients in sinus rhythm, a blunted heart rate reserve (HRR) during dipyridamole stress echocardiography (SE) is a prognostically unfavorable sign of cardiac autonomic dysfunction. In this study we sought to assess the prognostic meaning of HRR in patients with permanent atrial fibrillation (AF). The study population was made by 301 patients (176 men, age 73 ± 8 years) with suspected (n = 200) or known (n = 101) coronary artery disease and permanent AF who underwent high-dose dipyridamole SE. HRR was calculated on an average of 5 consecutive beats as the peak/rest ratio of HR from 12-lead EKG. During a median follow-up time of 77 months (first quartile 44, third quartile 115 months), 111 (37%) patients died. Receiver operating characteristics analysis identified HRR ≤1.17 as the best predictor of mortality. At multivariable analysis, HRR ≤1.17 (HR 1.75, 95% CI 1.17 to 2.62; p = 0.006) independently predicted mortality together with age (HR 1.09, 95% CI 1.06 to 1.13; p <0.0001), rest wall motion score index (HR 1.69, 95% CI 1.01 to 2.83; p = 0.04), and systemic hypertension (HR 1.76, 95% CI 1.06 to 3.00; p = 0.04). The annual mortality was 5.1% in the overall population, 7.0% in the 140 (46%) patients with abnormal HRR and 3.5% in the 161 (54%) patients with normal HRR. The 8-year mortality was 48% in patients with abnormal HRR and 18% in those with normal HRR (p <0.0001). In conclusion, patients with suspected or known coronary artery disease with permanent AF with a blunted HRR have an increased mortality. HRR outweighs inducible ischemia for prediction of survival. The assessment of HRR should become an integral part of dipyridamole SE reading also in AF.

Clinical, hemodynamic, and functional variables affecting success rate of coronary flow velocity reserve detection during vasodilator stress echocardiography.

AIM: Stress echocardiography (SE) with state-of-the-art imaging protocol allows a comprehensive assessment of regional wall-motion abnormalities and Doppler-based coronary flow velocity reserve (CFVR) in left anterior descending artery (LAD). We sought to assess the variables potentially impacting on success rate of SE with CFVR. METHODS AND RESULTS: In a single-center, prospective, observational study design, from 2007 to 2019, we enrolled 2989 consecutive patients (age 67 ± 12 years; 1723 men) referred for SE, without contrast, for chronic known (n = 1130) or suspected (n = 1859) coronary syndromes. Coronary flow velocity reserve was measured as stress/rest peak diastolic flow velocity. The same operator (LC) performed all examinations with the same machine (GE Vivid 7). Interpretable CFVR was obtained in 2808 patients (feasibility = 93.9%). Overall success rate was lowest (91.4%) in 2007-2008 and steadily rose to 97.8% in 2017-2019 (P for trend <.0001). Feasibility was excellent for men (93.7%) and women (94.3%) (P = .47) across all values of body mass index (BMI): <25 (P = .09), 25-29 (P = .84), and ≥30 (P = .23). At multivariable logistic regression analysis, women with BMI ≥ 30 (OR 1.94, 95% CI 1.14-3.29, P = .02), resting heart rate ≥77 beats/min (OR 2.25, 95% CI 1.64-3.11; P < .0001), and stress-induced ischemia in the LAD territory (OR 3.14, 95% CI 1.67-5.90; P < .0001) predicted unfeasible CFVR. CONCLUSION: Vasodilator SE with CFVR combined with wall-motion analysis is highly feasible also without contrast although with a slight decline in presence of high resting heart rate (reducing diastolic time essential for flow imaging), women with BMI ≥ 30 (increasing tissue thickness interposed between transducer and artery), and anterior ischemia (for underlying low-absent anterograde flow for severely stenotic or occluded LAD).

Prognostic value of heart rate reserve is additive to coronary flow velocity reserve during dipyridamole stress echocardiography.

BACKGROUND: During dipyridamole stress echocardiography (SE), a blunted heart rate reserve (HRR) is a prognostically unfavourable sign of cardiac autonomic dysfunction. AIM: To assess the prognostic meaning of HRR and coronary flow velocity reserve (CFVR). METHODS: The study group comprised 2149 patients (1236 men; mean age 66±12 years) with suspected (n=1280) or known (n=869) coronary artery disease and without inducible regional wall motion abnormalities (RWMA) during dipyridamole SE (0.84mg/kg in 6min). We assessed CFVR of the left anterior descending artery with pulsed-wave Doppler as the ratio between hyperaemic peak and basal peak diastolic flow velocities (abnormal value≤2.0). HRR was calculated as the peak/resting ratio of heart rate from a 12-lead electrocardiogram (abnormal value≤1.22). All patients were followed up. RESULTS: CFVR and HRR were abnormal in 520 (24%) and 670 (31%) patients, respectively. There was a positive linear correlation between CFVR and HRR (r=0.30; P<0.0001). During a median follow-up of 22 months (1st quartile 12 months, 3rd quartile 35 months), 75 (6%) patients died. The annual mortality was 1.6% in the overall population, 0.5% in the 1224 (57%) patients with normal CFVR and HRR, 1.7% in the 405 (19%) patients with abnormal HRR only, 3.6% in the 255 (12%) patients with abnormal CFVR only, and 6.2% in the 265 (12%) patients with abnormal CFVR and HRR. CONCLUSIONS: HRR is weakly related to CFVR, and a blunted HRR usefully complements RWMA and CFVR for prediction of outcome with dipyridamole SE. The patient without inducible RWMA is still at intermediate risk, but the risk is low with concomitant preserved CFVR, and very low with concomitant normal HRR.

Age- and Gender-Specific Prognostic Cutoff Values of Coronary Flow Velocity Reserve in Vasodilator Stress Echocardiography.

PURPOSE: Coronary flow velocity reserve (CFVR) of the left anterior descending artery is useful for risk stratification during stress echocardiography (SE) as an add-on to regional wall motion abnormalities (RWMA). We sought to provide sex- and age-specific prognostic cutoff values for CFVR. METHODS: A total of 5,577 patients (2,284 women; 110 age ≥ 85 years) who underwent dipyridamole SE with evaluation of RWMA and CFVR were enrolled in a multicenter prospective SE registry. Death and myocardial infarction were the clinical end points. RESULTS: During 20 months' median follow-up, 649 events (236 deaths, 413 infarctions) occurred: 288 in women and 38 in patients ≥85 years. At receiver operating characteristics analysis, the best prognostic cutoff value for CFVR was similar for men (2.03) and women (2.02) and consistent across all age strata (<45 years: 2.03; 45-54 years: 2.04; 45-64 years: 2.03; 65-74 and 75-84 years: 2.0) except for patients >85 years, who showed 1.90 as the optimal value. Independent predictors of mortality or myocardial infarction were RWMA (hazard ratio [HR] = 5.42), reduced CFVR (HR = 3.26), resting ejection fraction (HR = 0.98), smoking habit (HR = 1.41), age (HR = 1.02), and prior percutaneous coronary intervention (HR = 1.20) in patients age <85 years; and RWMA (HR = 5.42), smoking habit (HR = 3.24), and resting ejection fraction (HR = 0.97) in those age ≥85 years. CFVR added a prognostic contribution over clinical parameters, resting ejection fraction, and stress-induced RWMA in all age and sex groups except men >85 years. CONCLUSIONS: A sex-independent value of CFVR ≤2.0 provides the optimal prognostication across all age groups, except for those ≥85 years in whom a cutoff ≤1.90 is needed. Risk stratification is more effective for all age groups when CFVR is combined with RWMA.

Usefulness of Blunted Heart Rate Reserve as an Imaging-Independent Prognostic Predictor During Dipyridamole Stress Echocardiography.

A blunted heart rate (HR) response during dipyridamole myocardial perfusion imaging has been associated with a poor outcome. To assess the value of HR response in patients who underwent high-dose dipyridamole stress echocardiography (SE), we retrospectively selected a sample of 3,059 patients (none with pacemakers or atrial fibrillation; mean age 66 ± 11 years). All underwent high-dose (0.84 mg/kg) dipyridamole SE for evaluation of known or suspected coronary artery disease and/or heart failure in 2 laboratories of Pisa-IFC and Lucca. HR (with 12-lead ECG) was obtained each minute and recorded at rest and peak stress. HR reserve (HRR) was calculated as the peak/rest HR ratio. All patients were followed up. Patients were randomly divided into the modeling and validation group of equal size. During a median follow-up time of 1,004 days, 321 hard events occurred: 231 deaths and 90 nonfatal myocardial infarctions. HRR ≤ 1.22 identified by receiver operating characteristic analysis in the modeling group was an independent predictor of infarction-free survival in the modeling (hazard ratio 1.83, 95% confidence interval [CI] 1.30 to 2.60, p = 0.001), in the validation (hazard ratio 1.47, 95% CI 1.08 to 2.01, p = 0.02), and in the overall group (hazard ratio 1.60, 95% CI 1.27 to 2.02, p <0.0001), either off- or on-ß blockers. Five-year event rate increased from 8% to 24 % from the highest (≥1.41) to the lowest (≤1.14) HRR quartile. In conclusion, blunted HRR is a useful nonimaging predictor of adverse events during high-dose dipyridamole SE, independent of inducible ischemia, and beta-blocker therapy.

Apparent Declining Prognostic Value of a Negative Stress Echocardiography Based on Regional Wall Motion Abnormalities in Patients With Normal Resting Left Ventricular Function Due to the Changing Referral Profile of the Population Under Study.

Background Cardiology guidelines identify the low-risk response during stress echocardiography as the absence of regional wall motion abnormalities. Methods From 1983 to 2016, we enrolled 5817 patients (age 63±12 years; 2830 males) with suspected coronary artery disease, normal regional, and global left ventricular function at rest and during stress (exercise in 692, dipyridamole in 4291, and dobutamine in 834). Based on timing of enrollment, 4 groups were identified in chronological order of recruitment: years 1983 to 1989, group 1 (n=211); years 1990 to 1999, group 2 (n=1491); years 2000 to 2009, group 3 (n=3285); and years 2010 to 2016, group 4 (n=830). Results There were 240 (4%) events (119 deaths and 121 infarctions) in the follow-up. At 1-year follow-up, the event rate was 0.5% (95% CI, 0.05-0.95), 1.5% (95% CI, -1.18 to 1.82), 1.9% (95% CI, 1.63-2.17), and 1.7% (95% CI, 1.01-2.39; χ2, 9.0; P=0.03) in groups 1 to 4, respectively. At multivariable Cox analysis, independent predictors of future events were age (hazard ratio (HR), 1.05; 95% CI, 1.04-1.07; P<0.0001), male sex (HR, 1.57; 95% CI, 1.20-2.04; P=0.001), diabetes mellitus (HR, 1.78; 95% CI, 1.34-2.37; P<0.0001), smoking habit (HR, 1.40; 95% CI, 1.05-1.85; P=0.02), and ongoing anti-ischemic therapy (HR, 1.50; 95% CI, 1.15-1.97; P=0.003) Conclusions Over the past 3 decades, we observed a progressive decline in the prognostic value of a negative test based on regional wall motion abnormalities, likely reflecting both an increase in risk in patients, as well as a potential decrease in test performance due to concomitant anti-ischemic therapy.

Time Course of Ischemic and Bleeding Burden in Elderly Patients With Acute Coronary Syndromes Randomized to Low-Dose Prasugrel or Clopidogrel.

Background Elderly patients have high ischemic and bleeding rates after acute coronary syndrome; however, the occurrence of these complications over time has never been studied. This study sought to characterize average daily ischemic rates ( ADIRs ) and average daily bleeding rates ( ADBRs ) over 1 year in patients aged >74 years with acute coronary syndrome undergoing percutaneous coronary intervention who were randomized in the Elderly ACS 2 trial, comparing low-dose prasugrel (5 mg daily) with clopidogrel (75 mg daily). Methods and Results ADIRs and ADBRs were calculated as the total number of events, including recurrent events, divided by the number of patient-days of follow-up and assessed within different clinical phases: acute (0-3 days), subacute (4-30 days), and late (31-365 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparisons of ADIRs and ADBRs and the pairwise comparison of clopidogrel versus prasugrel effects. Globally, ADIRs were 2.6 times (95% CI, 2.4-2.9) higher than ADBRs . ADIRs were significantly higher in the clopidogrel arm than in the low-dose prasugrel arm in the subacute phase ( Padj<0.001) without a difference in ADBRs ( Padj=0.35). In the late phase, ADIRs remained significantly higher with clopidogrel ( Padj<0.001), whereas ADBRs were significantly higher with low-dose prasugrel ( Padj<0.001). Conclusions Ischemic burden was greater than bleeding burden in all clinical phases of 1-year follow-up of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. Low-dose prasugrel reduced ischemic events in the subacute and chronic phases compared with clopidogrel, whereas bleeding burden was lower with clopidogrel in the late phase. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01777503.

Prognostic value of dual imaging stress echocardiography following coronary bypass surgery.

AIMS: To assess the prognostic value of dual imaging stress echocardiography after coronary artery bypass grafting (CABG). Dual imaging stress echocardiography, combining the evaluation of regional wall motion and Doppler echocardiographic derived coronary flow velocity reserve (CFVR) of the left anterior descending artery (LAD), is the state-of-the-art methodology during vasodilatory stress. METHODS AND RESULTS: In a prospective, multicenter, observational study, 349 patients (270 men; 69 ±â€¯9 years; 262 symptomatic) with history of CABG underwent high-dose dipyridamole (0.84 mg/kg over 6 min) stress echocardiography with CFVR evaluation of LAD by Doppler. The composite endpoint of death and myocardial infarction was considered in the survival analysis. Positivity rate with either criteria was 13% in the 262 symptomatic patients with appropriate and 6% in the 87 asymptomatic patients with maybe/rarely appropriate indications on the basis of 2014 American College of Cardiology Foundation guidelines. During a median follow-up of 22 months (1st quartile 8, 3rd quartile 44), there were 56 (16%) events: 21 deaths, and 35 nonfatal myocardial infarctions. At Cox analysis, ischemia at stress echo (HR 4.80, 95% CI 2.69-8.55; p < 0.0001), and CFVR of LAD ≤2 (HR 2.28, 95% CI 1.32-3.95; p = 0.003) were multivariable prognostic predictors. Considering the group with no ischemia, patients with CFVR ≤2 showed 2.5 fold higher yearly hard events as compared to those with CFVR >2 (7.5 vs 2.9%; p = 0.002). CONCLUSIONS: Dual imaging stress echocardiography provides useful prognostic information following CABG. Inducible ischemia and abnormal CFVR are strong and independent prognostic indicators in patients with appropriate and rarely/maybe appropriate indications.

The Prognostic Value of Coronary Flow Velocity Reserve in Two Coronary Arteries During Vasodilator Stress Echocardiography.

BACKGROUND: Vasodilator stress echocardiography (SE) allows combined evaluation of regional wall motion and Doppler coronary flow velocity reserve (CFVR) of both the left anterior descending coronary artery (LAD) and the right coronary artery (RCA). The aim of this study was to prospectively assess the prognostic correlates of LAD and RCA CFVR on SE. METHODS: A total of 1,365 patients with known or suspected coronary artery disease underwent dipyridamole SE with combined evaluation of CFVR in both the LAD and the RCA. RESULTS: Ischemia was present on SE in 263 patients (19%). CFVR was abnormal (≤2.0) in 545 patients (40%): 172 in the LAD only, 149 in the RCA only, and 224 in both the LAD and the RCA. During a median follow-up period of 20 months, 44 deaths and 98 myocardial infarctions occurred. In the overall population, LAD CFVR ≤ 2.0 (hazard ratio [HR], 3.93) and inducible ischemia (HR, 2.74) were multivariate prognostic predictors. In the subset with ischemia on SE, CFVR did not add to peak wall motion score index (HR, 2.23). In patients without ischemia on SE, age (HR, 1.04), anti-ischemic therapy at the time of testing (HR, 1.6) and LAD CFVR ≤ 2.0 (HR, 10.8) were independent prognostic indicators. In patients without ischemia on SE and LAD CFVR >2.0, the 4-year event rate was 4% in those with RCA CFVR > 2.0 and 18% in those with RCA CFVR ≤ 2.0 (P < .0001). CONCLUSIONS: Ischemia on SE with high peak wall motion score index identifies a high-risk subset regardless of the underlying CFVR response. Absence of ischemia on SE is associated with intermediate risk, and LAD CFVR is essential to identify a truly low-risk subset. RCA CFVR is less useful than LAD CFVR but may have a role for further risk stratification in patients without ischemia and normal LAD CFVR.

Drop-off in positivity rate of stress echocardiography based on regional wall motion abnormalities over the last three decades.

Previous studies have suggested a decline in positivity of stress cardiac imaging based on regional wall motion abnormalities (RWMA). To assess the rate of RWMA positivity of stress echocardiography (SE) over 3 decades in the same primary care SE lab. We retrospectively assessed the rate of SE positivity in 7626 SE tests (dipyridamole in 5053, dobutamine in 2496, exercise in 77) in consecutive patients with known or suspected coronary artery disease and /or heart failure who performed SE in a primary care referral center from April 1991 to May 2018. Starting April 2005, SE based on RWMA was complemented by assessment of coronary flow velocity reserve (CFVR) of the left anterior descending coronary artery. Starting October 2016, we added left ventricular contractile reserve (LVCR). Starting October 2016, we also added B-lines by lung ultrasound. There was a progressive decline over time in the rate of SE positivity based on RWMA from 24% (1991-1999) to 10% (2000-2009) down to 4% (2010-2018) (p < 0.0001). Positivity rate was 29% with CFVR, 16% with LVCR, and 12% with B-lines. Over three decades, we observed a dramatic decline in SE positivity rate based on classical RWMA. In the last decade, the positivity rate rose sharply thanks to the stepwise introduction of CFVR, LVCR and B-lines as additional positivity criteria in integrated quadruple SE.

Integration of Wall Motion, Coronary Flow Velocity, and Left Ventricular Contractile Reserve in a Single Test: Prognostic Value of Vasodilator Stress Echocardiography in Patients with Diabetes.

BACKGROUND: Coronary flow velocity reserve (CFVR) and left ventricular contractile reserve (LVCR) have demonstrated prognostic importance in patients with diabetes. The aim of this study was to investigate the prognostic contribution of combined evaluation of CFVR and LVCR in patients with diabetes with nonischemic stress echocardiography. METHODS: Three hundred seventy-five patients with diabetes (mean age, 68 ± 9 years) with nonischemic dipyridamole stress echocardiography underwent assessment of CFVR of the left anterior descending coronary artery (prospectively) and LVCR with left ventricular force (retrospectively) in a multicenter study. RESULTS: On receiver operating characteristic analysis, LVCR ≤ 1.1 was the best prognostic predictor and was considered an abnormal value. CFVR was abnormal (≤2) in 139 patients (37%), LVCR in 156 (42%), neither in 157 (42%), and both in 77 (21%). During a median follow-up period of 16 months, 86 major adverse cardiac events occurred: 16 deaths, 13 myocardial infarctions, and 57 revascularizations. Multivariate prognostic indicators were CFVR ≤ 2 (P < .0001), age (P = .03), and LVCR ≤ 1.1 (P = .04). The 3-year rate of major adverse cardiac events was 63% in patients with both abnormal CFVR and LVCR, 42% in those with abnormal CFVR only, 19% in those with abnormal LVCR only, and 10% in patients with both normal CFVR and LVCR. The 3-year hard event rate was 3% in patients with both normal CFVR and LVCR, fivefold higher in patients with abnormal CFVR or LVCR only, and ninefold higher in patients with both abnormal CFVR and LVCR. CONCLUSIONS: Patients with diabetes with nonischemic dipyridamole stress echocardiography may still have significant risk in presence of abnormal CFVR and/or LVCR, which assess the underlying, largely unrelated, microvascular and myocardial components of coronary circulation.