Sabrina Molinaro

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.

Cardiac Magnetic Resonance Predicts Outcome in Patients With Premature Ventricular Complexes of Left Bundle Branch Block Morphology

OBJECTIVES We investigated whether the presence of right ventricular (RV) abnormalities detected by cardiovascular magnetic resonance (CMR) predict adverse outcome in patients presenting with frequent premature ventricular complexes (PVCs) of left bundle branch block (LBBB) morphology. BACKGROUND CMR is a component of the diagnostic workup for the differential diagnosis between arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) and idiopathic RV tachycardia. RV abnormalities evaluated by CMR could have prognostic importance. METHODS Four hundred forty consecutive patients with >1,000 PVCs of LBBB morphology (minor diagnostic criterion of ARVC/D) and no other pre-existing criteria were prospectively enrolled. RV wall motion (WM), signal abnormalities, dilation, and reduced ejection fraction evaluated by CMR were considered imaging criteria of ARVC/D. Follow-up was performed evaluating an index composite end point of 3 cardiac events: cardiac death, resuscitated cardiac arrest, and appropriate implantable cardiac-defibrillator shock. RESULTS Subjects with multiple RV abnormalities (RVA-2 group) had worse outcome than the no-RVA group (hazard ratio [HR]: 48.6; 95% confidence interval [CI]: 6.1 to 384.8; p < 0.001). Of the 61 patients in the RVA-2 group, only 6 had a definite diagnosis of ARVC/D applying the Task Force Criteria. Also, subjects with a single imaging criterion (RVA-1 group) had worse outcome than the no-RVA group (HR: 18.2; 95% CI: 2.0 to 162.6; p = 0.01). Patients with only WM abnormalities had higher prevalence of cardiac events than no-RVA (HR: 27.2; 95% CI: 3.0 to 244.0; p = 0.03). CONCLUSIONS In subjects with frequent PVC of LBBB morphology, CMR allows risk stratification. RV abnormalities were associated with worse outcome.

Prognostic Value of High-Dose Dipyridamole Stress Myocardial Contrast Perfusion Echocardiography

Background— The addition of myocardial perfusion (MP) imaging during dipyridamole real-time contrast echocardiography improves the sensitivity to detect coronary artery disease, but its prognostic value to predict hard cardiac events in large numbers of patients with known or suspected coronary artery disease remains unknown. Methods and Results— We studied 1252 patients with the use of dipyridamole real-time contrast echocardiography and followed them for a median of 25 months. The prognostic value of MP imaging regarding death and nonfatal myocardial infarction was determined and related to wall motion (WM), clinical risk factors, and rest ejection fraction by the use of Cox proportional-hazards models, C index, and risk reclassification analysis. A total of 59 hard events (4.7%) occurred during the follow-up (24 deaths, 35 myocardial infarctions). The 2-year event-free survival was 97.9% in patients with normal MP and WM, 91.9% with isolated reversible MP defects but normal WM, and 67.4% with both reversible MP and WM abnormalities (P<0.001). By multivariate analysis the independent predictors of events were age (hazard ratio 1.05, 95% confidence interval [CI], 1.02–1.08), sex (hazard ratio, 2.36; 95% CI, 1.32–4.23), reversible MP defects (hazard ratio, 3.88; 95% CI, 1.83–8.21), and reversible WM abnormalities with reversible MP defects (hazard ratio, 4.51; 95% CI, 2.25–9.07). Reversible MP defects added incremental predictive value and reclassification benefit over WM response and clinical factors (P=0.001). Conclusions— MP imaging using real-time perfusion echocardiography during dipyridamole real-time contrast echocardiography provides independent, incremental prognostic information regarding hard cardiac events in patients with known or suspected coronary artery disease. Patients with normal MP responses have better outcome than patients with normal WM; patients with both reversible WM and MP abnormalities have the worst outcome.

Contrast Stress-Echocardiography Predicts Cardiac Events in Patients with Suspected Acute Coronary Syndrome but Nondiagnostic Electrocardiogram and Normal 12-Hour Troponin

BACKGROUND No large study has demonstrated that any stress test can risk-stratify future hard cardiac events (cardiac death or myocardial infarction) in patients with suspected acute coronary syndromes (ACS), nondiagnostic electrocardiographic (ECG) findings, and normal troponin levels. The aim of this study was to test the hypothesis that combined contrast wall motion and myocardial perfusion echocardiographic assessment (cMCE) during stress echocardiography can predict long-term hard cardiac events in patients with suspected ACS, nondiagnostic ECG findings, and normal troponin. METHODS A total of 545 patients referred for contrast stress echocardiography from the emergency department for suspected ACS but nondiagnostic ECG findings and normal troponin levels at 12 hours were followed up for cardiac events. Patients underwent dipyridamole-atropine echocardiography with adjunctive myocardial perfusion imaging using a commercially available ultrasound contrast medium (SonoVue). RESULTS During a median follow-up period of 12 months, 25 cardiac events (4.6%) occurred (no deaths, 12 nonfatal myocardial infarctions, 13 episodes of unstable angina). Abnormal findings on cMCE were the most significant predictor of both hard cardiac events (hazard ratio, 22.8; 95% confidence interval, 2.9-176.7) and the combined (cardiac death, myocardial infarction, or unstable angina requiring revascularization) end point (hazard ratio, 10.7; 95% confidence interval, 3.7-31.3). The inclusion of the cMCE variable significantly improved multivariate models, determining lower Akaike information criterion values and higher discrimination ability. CONCLUSIONS cMCE during contrast stress echocardiography provided independent information for predicting hard and combined cardiac events beyond that predicted by stress wall motion abnormalities in patients with suspected ACS, nondiagnostic ECG findings, and normal troponin levels.

Comparative prediction of cardiac events by wall motion, wall motion plus coronary flow reserve, or myocardial perfusion analysis: a multicenter study of contrast stress echocardiography

OBJECTIVES This study sought to determine whether the increasing difficulty of assessing wall motion (WM), Doppler coronary flow reserve on the left anterior descending coronary artery (CFR-LAD), and myocardial perfusion (MP) during stress echocardiography (SE) was justified by increasing prognostic information in patients with known or suspected coronary artery disease. BACKGROUND The use of echocardiographic contrast agents during SE permits the assessment of both CFR-LAD and MP, but their relative incremental prognostic value is undefined. METHODS This study followed a multicenter cohort of 718 patients for 16 months after high-dose dipyridamole contrast SE for evaluation of known or suspected coronary artery disease. The ability of WM, CFR-LAD, and MP to predict cardiac events was studied by multivariable models and risk reclassification. RESULTS Abnormal SE was detected as a reversible WM abnormality in 18%, reversible MP defect in 27%, and CFR-LAD <2 in 38% of subjects. Fifty cardiac events occurred (annualized event rate 6.0%). A normal MP stress test had a 1-year hard event rate of 1.2%. The C-index of outcomes prediction based on clinical data was improved with MP (p < 0.001) and WM/CFR-LAD (p = 0.037), and MP (p = 0.003) added to clinical and WM data. Net risk reclassification was improved by adding MP (p < 0.001) or CFR-LAD (net reclassification improvement p = 0.001) in addition to clinical and WM data. The model including clinical data, WM/CFR-LAD, and MP performed better than that without MP did (p = 0.012). CONCLUSIONS The multiparametric assessment of WM, CFR-LAD and MP during stress testing in patients with known or suspected coronary artery disease is feasible. Contrast SE allowed better prognostication, irrespective of the use of CFR-LAD or MP. The addition of either CFR-LAD or MP assessment to standard WM analysis and clinical parameters yielded progressively higher values for the prediction of cardiac events and may be required in todays intensively treated patients undergoing SE, because their average low risk of future cardiac events requires methods with higher predictive sensitivity than that available with standalone WM assessment.

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.

Scar extent, left ventricular end-diastolic volume and wall motion abnormalities identify high-risk patients with previous myocardial infarction: a multiparametric approach for prognostic stratification

AIMS We sought to investigate whether combining left ventricular (LV) volumes, regional wall motion abnormalities, and scar tissue extent obtained by cardiac magnetic resonance (CMR) improves risk stratification of patients with previous myocardial infarction (MI). METHODS AND RESULTS In 231 consecutive patients (age 64 ± 11 years, males 89%) with previous MI, we quantified LV volumes and regional wall motion abnormalities by cine CMR, and measured the extent of the infarction scar by late gadolinium enhancement (LGE). During follow-up (median, 3.2 years) cardiac events (cardiac death or appropriate intra-cardiac defibrillator shocks) occurred in 19 patients. After adjustment for age, an extent of LGE >12.7%, an LV end-diastolic volume >105 mL/m(2), and a wall motion score index >1.7 were independent associated with adverse cardiac events at multivariate analysis (P < 0.05, P < 0.001, and P < 0.01, respectively). The patients with none of these factors, and those with one or two factors, showed a lower risk of cardiac events [hazard ratio (HR) = 0.112, P < 0.01 and HR = 0.261, P < 0.05] than those with three factors. The cumulative event-rate estimated at 4 years was 29.6% in patients with all three factors, 7.7% in those with one or two factors, and 3.5% in patients with none of these factors. CONCLUSION A multiparametric CMR approach, which includes the measure of scar tissue extent, LV end-diastolic volume and regional wall motion abnormalities, improves risk stratification of patients with previous MI.

Persistence of Mortality Risk in Patients With Acute Cardiac Diseases and Mild Thyroid Dysfunction

Introduction:There are no studies on the long-term prognostic role of abnormal thyrotropin value in patients with acute cardiac diseases. Aim of the study was to assess the incidence and persistence of risk of cardiac and overall deaths in patients with acute cardiac diseases. Methods:A total of 1026 patients (mean age: 67.7 years) were divided into 4 groups: (1) euthyroid (EU, n=579); (2) subclinical-like hypothyroidism (SLHYPO, n=68); (3) subclinical-like hyperthyroidism (SLHYPER, n=23) and (4) low-triiodothyronine syndrome (LowT3, n=356). Follow-up started from the day of thyroid hormone evaluation (mean follow-up: 30 months). The events considered were cardiac and overall deaths. Results:Survival rate for cardiac death was lower in SLHYPO and in LT3 than in EU (log rank test; &khgr;2=33.6; P < 0.001). Survival rate for overall death was lower in SLHYPO, SLHYPER and LowT3 than in EU (48.3; P < 0.001). After adjustment for several risk factors, the hazard ratio for cardiac death was higher in SLHYPO (3.65; P=0.004) in LowT3 (1.88; P=0.032) and in SLHYPER (4.73; P=0.047). Hazard ratio for overall death was higher in SLHYPO (2.30; P=0.009), in LowT3 (1.63; P=0.017) and in SLHYPER than in EU (3.71; P=0.004). Hazards for SLHYPO, SLHYPER and LowT3 with respect to EU were proportional over the follow-up period. Conclusion:In patients with acute cardiac disease, a mildly altered thyroid status was associated with increased risk of mortality that remains constant during all the follow-up.

Prognostic Implication of Appropriateness Criteria for Pharmacologic Stress Echocardiography Performed in an Outpatient Clinic

Background— Although appropriateness criteria for stress echocardiography have been developed to deliver high-quality care, the prognostic impact of these criteria remains undefined. Therefore, we sought to assess the prognostic implication of the American College of Cardiology/American Society of Echocardiography appropriateness criteria for pharmacological stress echo in a cohort of ambulatory patients. Methods and Results— The study population consisted of 1552 ambulatory patients who underwent pharmacological (752 dobutamine, 800 dipyridamole) stress echo for the evaluation of known (n=549) or suspected (n=1003) coronary artery disease at a single cardiology center. Patients were followed up for a median of 36 months. Indications were determined for consecutive studies by 2 reviewers and categorized as follows: 984 (63%) patients had appropriate, 145 (9%) uncertain, and 423 (27%) inappropriate indication for stress echo. Ischemia was present in 15% of patients with appropriate, 8% of those with uncertain, and 5% of those with inappropriate indication (P<0.0001). During follow-up, 146 events (89 deaths, 57 nonfatal infarctions) occurred. Annual event rate associated with appropriate, uncertain, and inappropriate study was 3.1%, 3.8%, and 1.3%, respectively. The abnormal test result in patients with appropriate, uncertain, and inappropriate study was associated with 5.0%, 5.6%, and 1.8% annual event rate, respectively, exerting an independent value only in the appropriate and uncertain subset. Conclusions— Inappropriate indication for pharmacological stress echo is common, being documented in about 1 of 4 patients evaluated in an ambulatory setting, and is associated with lower rate of positive results and better survival as compared with appropriate and uncertain indication.

Illegal Substance Use among Italian High School Students: Trends over 11 Years (1999–2009)

Purpose To monitor changes in habits in drug use among Italian high school students. Methods Cross-sectional European School Survey Project on Alcohol and Other Drugs (ESPAD) carried out in Italy annually for 11 years (1999–2009) with representative samples of youth attending high school. The sample size considered ranges from 15,752 to 41,365 students and response rate ranged from 85.5% to 98.6%. Data were analyzed to obtain measures of life-time prevalence (LT), use in the last year (LY), use in the last 30 days (LM), frequent use. Comparisons utilized difference in proportion tests. Tests for linear trends in proportion were performed using the Royston p trend test. Results When the time-averaged value was considered, cannabis (30% LT) was the most, and heroin the least (2%) frequently used, with cocaine (5%), hallucinogens (2%) and stimulants (2%) in between. A clear gender gap is evident for all drugs, more obvious for hallucinogens (average M/F LY prevalence ratio 2, range 1.7–2.4, p<0.05), less for cannabis (average M/F LY prevalence ratio 1.3, range 1.2–1.5, p<0.05). Data shows a change in trend between 2005 and 2008; in 2006 the trend for cannabis use and availability dropped and the price rose, while from 2005 cocaine and stimulant use prevalence showed a substantial increase and the price went down. After 2008 use of all substances seems to have decreased. Conclusions Drug use is widespread among students in Italy, with cannabis being the most and heroin the least prevalent. Girls are less vulnerable than boys to illegal drug use. In recent years, a decrease in heroin use is overbalanced by a marked rise in hallucinogen and stimulant use.