Francesco Bovenzi

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

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.

Contemporary antithrombotic strategies in patients with acute coronary syndrome admitted to cardiac care units in Italy: The EYESHOT Study

Background: Several new antithrombotic therapies have emerged for the treatment of acute coronary syndrome (ACS). We sought to assess contemporary patterns of antithrombotic therapies use in patients with ACS. Methods and results: EYESHOT (EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units) was a nationwide, prospective registry aimed to evaluate antithrombotic strategies employed in patients admitted to intensive cardiac care units (CCUs) for an ACS in Italy. Over a three-week period, 203 CCUs enrolled 2585 consecutive patients: 41.2% with ST-elevation myocardial infarction (STEMI) and 58.8% with non-ST elevation ACS (NSTE-ACS). During hospitalisation, low-molecular-weight heparins, aspirin, and clopidogrel were the most commonly used antithrombotic therapies. Among patients treated with percutaneous coronary intervention (PCI, n=1755), any crossover of heparin therapy occurred in 30.8% of cases, while switching from one P2Y12 inhibitor to another occurred in 3.6% of cases in the CathLab and in 14.2% before discharge. Of the 790 patients who did not receive revascularisation, switching of a P2Y12 inhibitor occurred in 5.7% of cases. At discharge, a new P2Y12 inhibitor (ticagrelor or prasugrel) in association with aspirin was prescribed in 59.5% of STEMI and 33.9% of NSTE-ACS patients: the most powerful predictor for prescription was PCI (odds ratio (OR) 6.18; 95% confidence interval (CI) 4.76–8.01; p<0.0001), whereas age ≥75 years was strongly associated with clopidogrel use (OR 0.28; 95% CI 0.22–0.36; p<0.0001). Conclusions: The EYESHOT registry shows the current pattern of antithrombotic treatments for ACS patients admitted to Italian CCUs and provides insights which may help to improve the clinical care of such patients.

Nonpharmacologic Care of Heart Failure: Counseling, Dietary Restriction, Rehabilitation, Treatment of Sleep Apnea, and Ultrafiltration

The prognosis of patients with chronic congestive heart failure (CHF) depends not only on pharmacologic therapy but also on nonpharmacologic aspects. A complete and ongoing education program for treating CHF includes an understanding of the causes of CHF, symptoms, diet, salt and fluid restriction, drug regimen, compliance, physical and work activities, lifestyle changes, and measures of self-control. Moreover, the nonpharmacologic treatment (dietary modifications, lifestyle, physical exercise, and health care education) must be inserted in a multidisciplinary program organized by the physician in conjunction with the health system, the nurses, and, especially, the patients themselves, who must understand their disease and the many therapeutic options. Cardiologists should treat patients in a clear and comprehensible way, and other specialists (dietitians, physiotherapists, psychologists, nurses, and social workers), together with the patients family, should strive for the best living conditions for the patient. In this way, the treatment of CHF can improve the quantity and quality of life and save a significant amount in health care costs.

Perioperative management of antiplatelet therapy in patients with coronary stents undergoing cardiac and non-cardiac surgery: a consensus document from Italian cardiological, surgical and anaesthesiological societies

Optimal perioperative antiplatelet therapy in patients with coronary stents undergoing surgery still remains poorly defined and a matter of debate among cardiologists, surgeons and anaesthesiologists. Surgery represents one of the most common reasons for premature antiplatelet therapy discontinuation, which is associated with a significant increase in mortality and major adverse cardiac events, in particular stent thrombosis. Clinical practice guidelines provide little support with regard to managing antiplatelet therapy in the perioperative phase in the case of patients with non-deferrable surgical interventions and/or high haemorrhagic risk. Moreover, a standard definition of ischaemic and haemorrhagic risk has never been determined. Finally, recommendations shared by cardiologists, surgeons and anaesthesiologists are lacking. The present consensus document provides practical recommendations on the perioperative management of antiplatelet therapy in patients with coronary stents undergoing surgery. Cardiologists, surgeons and anaesthesiologists have contributed equally to its creation. On the basis of clinical and angiographic data, the individual thrombotic risk has been defined. All surgical interventions have been classified according to their inherent haemorrhagic risk. A consensus on the optimal antiplatelet regimen in the perioperative phase has been reached on the basis of the ischaemic and haemorrhagic risk. Aspirin should be continued perioperatively in the majority of surgical operations, whereas dual antiplatelet therapy should not be withdrawn for surgery in the case of low bleeding risk. In selected patients at high risk for both bleeding and ischaemic events, when oral antiplatelet therapy withdrawal is required, perioperative treatment with short-acting intravenous glycoprotein IIb/IIIa inhibitors (tirofiban or eptifibatide) should be taken into consideration.

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.

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.

Temporal trends in the epidemiology, management, and outcome of patients with cardiogenic shock complicating acute coronary syndromes.

Despite advances in the management of patients with acute coronary syndrome (ACS), cardiogenic shock (CS) remains the leading cause of death in these patients. We describe the evolution of clinical characteristics, in‐hospital management, and outcome of patients with CS complicating ACS.

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 (<or=1.80) was associated with a worse (p <0.0001) event rate than other quartiles in the entire population and in patients with no ischemia at stress echocardiography. Furthermore, the second quartile of CFR (1.81 to 2.16) was predictive of increased (p <0.0001) risk compared to the higher quartiles. In conclusion, Doppler echocardiographically derived CFR in LAD is a strong and independent prognostic predictor in patients with known or suspected CAD, but the spectrum of prognostic stratifications is expanded if the response is titrated according to a continuous scale rather than artificially dichotomized.

Prediction of Mortality by Stress Echocardiography in 2835 Diabetic and 11 305 Nondiabetic Patients

Background—To compare the capability by stress echocardiography results to predict overall mortality in a large unselected cohort of diabetic and nondiabetic patients. Methods and Results—The study group comprised 14 140 patients (2835 diabetics and 11 305 nondiabetics) who underwent stress echocardiography for evaluation of known (n=5671) or suspected (n=8469) coronary artery disease. Ischemia at stress echocardiography was observed in 768 (27%) diabetics and 2644 (23%) nondiabetics. During a median follow-up of 30 months (first quartile, 9; third quartile, 63), 1213 patients died. In diabetics, multivariable indicators of mortality were age (hazard ratio [HR], 1.07, 95% confidence interval [CI], 1.06–1.09), rest wall motion abnormality (HR, 2.43; 95% CI, 1.83–3.22), and ischemia at stress echocardiography (HR, 1.71; 95% CI, 1.34–2.18). In nondiabetics, multivariable indicators of mortality were age (HR, 1.07; 95% CI, 1.06–1.08), rest wall motion abnormality (HR, 2.19; 95% CI, 1.86–2.57), male sex (HR, 1.65; 95% CI, 1.41–1.93), ischemia at stress echocardiography (HR, 1.54; 95% CI, 1.32–1.80), and antischemic therapy at the time of test (HR, 1.15; 95% CI, 1.00–1.32). In stress echo negative subjects for ischemia, antischemic therapy showed increased annual mortality in nondiabetic patients with (3.8% versus 3.1%; P=0.04) or without rest wall motion abnormality (1.6% versus 0.9%; P<0.0001); it failed to do so in diabetic patients with (5.7% versus 5.8%; P=0.89) or without rest wall motion abnormality (2.6% versus 1.9%; P=0.10). Conclusions—Ischemia at stress echocardiography is a strong and independent predictor of total mortality in diabetic as well as nondiabetic patients. Antischemic therapy markedly affects the negative predictive value of stress echocardiography in nondiabetic patients, whereas it is prognostically neutral in the diabetic population.