Machine learning to identify a composite indicator to predict cardiac death in ischemic heart disease.

BACKGROUND: Machine learning (ML) employs algorithms that learn from data, building models with the potential to predict events by aggregating a large number of variables and assessing their complex interactions. The aim of this study is to assess ML potential in identifying patients with ischemic heart disease (IHD) at high risk of cardiac death (CD). METHODS: 3987 (mean age 68 ± 11) hospitalized IHD patients were enrolled. We implemented and compared various ML models and their combination into ensembles. Model output constitutes a new ML indicator to be employed for stratification. Primary variable importance was assessed with ablation tests. RESULTS: An ensemble classifier combining three ML models achieved the best performance to predict CD (AUROC of 0.830, F1-macro of 0.726). ML indicator use through Cox survival analysis outperformed the 18 variables individually, producing a better stratification compared to standard multivariate analysis (improvement of ∼20%). Patients in the low risk group defined through ML indicator had a significantly higher survival (88.8% versus 29.1%). The main variables identified were Dyslipidemia, LVEF, Previous CABG, Diabetes, Previous Myocardial Infarction, Smoke, Documented resting or exertional ischemia, with an AUROC of 0.791 and an F1-score of 0.674, lower than that of 18 variables. Both code and clinical data are freely available with this article. CONCLUSION: ML may allow a faster, low-cost and reliable evaluation of IHD patient prognosis by inclusion of more predictors and identification of those more significant, improving outcome prediction towards the development of precision medicine in this clinical field.

Lipoprotein(a), Cardiovascular Events and Sex Differences: A Single Cardiological Unit Experience.

Lipoprotein(a)-Lp(a), which retains proatherogenic and prothrombotic properties, may be modified by hormonal and metabolic factors. However, few studies have focused on differences related to sex and cardiometabolic risk factors in the relationship between Lp(a) and cardiovascular disease, especially in terms of prognosis. This study aimed at evaluating the predictive value of Lp(a) (cut-off 30 mg/dL) for hard events (HEs: mortality and non-fatal myocardial infarction) according to sex and cardiometabolic risk factors in 2110 patients (1501 males, mean age: 68 ± 9 years) undergoing coronary angiography for known or suspected coronary artery disease. There were 211 events over a median follow-up period of 33 months. Lp(a) > 30 mg/dL did not confer a worse prognosis on the overall population. However, Kaplan-Meier subgroup analysis evidenced a worse prognosis in type 2 diabetes (T2D) females with elevated Lp(a) (log-rank test: p = 0.03) vs. T2D males and no-T2D patients, but not in other high-risk cardiovascular states (e.g., smoking, hypertension, reduced left ventricular ejection fraction or obesity). After Cox multivariate adjustment, Lp(a) remained an independent determinant for HEs in the T2D female subgroup, conferring an HR of 2.9 (95% CI 1.1-7.7, p < 0.05). Lp(a) is therefore a strong independent predictor of HR in T2D women, but not in T2D men, or in noT2D patients.

Interaction of Uric Acid and Neutrophil-to-Lymphocyte Ratio for Cardiometabolic Risk Stratification and Prognosis in Coronary Artery Disease Patients.

Oxidative stress and inflammation are key factors in cardiometabolic diseases. We set out to evaluate the relationship between serum uric acid (UA) and the neutrophil-to-lymphocyte ratio (NLR) with cardiometabolic risk factors in coronary artery disease (CAD) patients, and their additive and multiplicative interactive effects on outcomes (cardiac death/CD and hard events (HE)-death plus reinfarction). A total of 2712 patients (67 ± 11 years, 1960 males) who underwent coronary angiography was retrospectively analyzed and categorized into no-CAD patients (n =806), stable-CAD patients (n =1545), and patients with acute myocardial infarction (AMI) (n =361). UA and NLR were reciprocally correlated and associated with cardiometabolic risk factors. During a mean follow-up period of 27 ± 20 months, 99-3.6% deaths, and 213-7.8% HE were registered. The Kaplan-Meier survival estimates showed significantly worse outcomes in patients with elevated UA or NLR levels. Multivariate Cox regression analysis demonstrated that NLR independently predicted CD and HE. There was no multiplicative interaction between UA and NLR; however, the use of measures of additive interaction evidenced a positive additive interaction between UA and NLR for CD and HE. Although it is clear that correlation does not imply causation, the coexistence of NRL and UA appears to have a synergistic effect, providing further information for the risk stratification of CAD patients.

FIB-4 Index and Neutrophil-to-Lymphocyte-Ratio as Death Predictor in Coronary Artery Disease Patients.

Nonalcoholic fatty liver disease (NAFLD)-associated liver fibrosis is likely related to coronary artery disease (CAD) by the mediation of systemic inflammation. This study aimed at evaluating the predictive value of neutrophil-to-lymphocyte-ratio (NLR) and fibrosis-4 index (FIB-4), indices of inflammation and fibrosis, respectively, on CAD mortality. Data from 1460 CAD patients (1151 males, age: 68 ± 10 years, mean ± SD) were retrospectively analyzed. Over a median follow-up of 26 months (interquartile range (IQR) 12−45), 94 deaths were recorded. Kaplan−Meier survival analysis revealed worse outcomes in patients with elevation of one or both biomarkers (FIB-4 > 3.25 or/and NLR > 2.04, log-rank p-value < 0.001). In multivariate Cox regression analysis, the elevation of one biomarker (NLR or FIB-4) still confers a significant independent risk for mortality (hazard ratio (HR) = 1.7, 95% confidence interval (95% CI): 1.1−2.7, p = 0.023), whereas an increase in both biomarkers confers a risk corresponding to HR = 3.5 (95% CI: 1.6−7.8, p = 0.002). Categorization of patients with elevated FIB-4/NLR could provide valuable information for risk stratification and reduction of residual risk in CAD patients.

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.

Uncovering the eruptive patterns of the 2019 double paroxysm eruption crisis of Stromboli volcano.

In 2019, Stromboli volcano experienced one of the most violent eruptive crises in the last hundred years. Two paroxysmal explosions interrupted the 'normal' mild explosive activity during the tourist season. Here we integrate visual and field observations, textural and chemical data of eruptive products, and numerical simulations to analyze the eruptive patterns leading to the paroxysmal explosions. Heralded by 24 days of intensified normal activity and 45 min of lava outpouring, on 3 July a paroxysm ejected ~6 × 107 kg of bombs, lapilli and ash up to 6 km high, damaging the monitoring network and falling towards SW on the inhabited areas. Intensified activity continued until the less energetic, 28 August paroxysm, which dispersed tephra mainly towards NE. We argue that all paroxysms at Stromboli share a common pre-eruptive weeks-to months-long unrest phase, marking the perturbation of the magmatic system. Our analysis points to an urgent implementation of volcanic monitoring at Stromboli to detect such long-term precursors.

Prognostic value of lung ultrasound in patients hospitalized for heart disease irrespective of symptoms and ejection fraction.

AIMS: Lung ultrasound B-lines are the sonographic sign of pulmonary congestion and can be used in the differential diagnosis of dyspnoea to rule in or rule out acute heart failure (AHF). Our aim was to assess the prognostic value of B-lines, integrated with echocardiography, in patients admitted to a cardiology department, independently of the initial clinical presentation, thus in patients with and without AHF, and in AHF with reduced and preserved ejection fraction (HFrEF and HFpEF). METHODS AND RESULTS: We enrolled consecutive patients admitted for various cardiac conditions. Patients were classified into three groups: (i) acute HFrEF; (ii) acute HFpEF; and (iii) non-AHF. All patients underwent an echocardiogram coupled with lung ultrasound at admission, according to standardized protocols. We followed up 1021 consecutive inpatients (69 ± 12 years) for a median of 14.4 months (interquartile range 4.6-24.3) for death and rehospitalization for AHF. During the follow-up, 126 events occurred. Admission B-lines > 30, ejection fraction < 50%, tricuspid regurgitation velocity > 2.8 m/s, and tricuspid annular plane systolic excursion < 17 mm were independent predictors at multivariable analysis. B-lines > 30 had a strong predictive value in HFpEF and non-AHF, but not in HFrEF. CONCLUSIONS: Ultrasound B-lines can detect subclinical pulmonary interstitial oedema in patients thought to be free of congestion and provide useful information not only for the diagnosis but also for the prognosis in different cardiac conditions. Their added prognostic value among standard echocardiographic parameters is more robust in patients with HFpEF compared with HFrEF.

Major explosions and paroxysms at Stromboli (Italy): a new historical catalog and temporal models of occurrence with uncertainty quantification.

Stromboli volcano (Italy), always active with low energy explosive activity, is a very attractive place for visitors, scientists, and inhabitants of the island. Nevertheless, occasional more intense eruptions can present a serious danger. This study focuses on the modeling and estimation of their inter-event time and temporal rate. With this aim we constructed a new historical catalog of major explosions and paroxysms through a detailed review of scientific literature of the last ca. 140 years. The catalog includes the calendar date and phenomena descriptions for 180 explosive events, of which 36 were paroxysms. We evaluated the impact of the main sources of uncertainty affecting the historical catalog. In particular, we categorized as uncertain 45 major explosions that reportedly occurred before 1985 and tested the effect of excluding these events from our analysis. Moreover, after analyzing the entire record in the period [1879, 2020], we separately considered, as sequences, events in [1879, 1960] and in [1985, 2020] because of possible under recording issues in the period [1960, 1985]. Our new models quantify the temporal rate of major explosions and paroxysms as a function of time passed since the last event occurred. Recurrence hazard levels are found to be significantly elevated in the weeks and months following a major explosion or paroxysm, and then gradually decrease over longer periods. Computed hazard functions are also used to illustrate a methodology for estimating order-of-magnitude individual risk of fatality under certain basis conditions. This study represents a first quantitatively formal advance in determining long-term hazard levels at Stromboli.

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.

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.

Long-term prognosis of unheralded myocardial infarction vs chronic angina; role of sex and coronary atherosclerosis burden.

BACKGROUND: Angina pectoris (AP) and unheralded myocardial infarction (MI) are considered random clinical equivalents of ischemic heart disease (IHD). Aim of the study was to evaluate the long-term progression of AP as opposed to unheralded MI as alternative first clinical presentations of IHD and the effect of sex on prognosis. METHODS: The study included 2272 consecutive patients, 1419 MI and 1353 AP, hospitalized from 1995 to 2007 at CNR Clinical Physiology Institute, Pisa, Italy and followed up to December 2013, who fulfilled the following criteria: unheralded MI or AP as first manifestation of IHD; age < = 70 years; known coronary anatomy; at least 10-year follow-up. Fatal and non fatal MI, all-cause, and cardiac deaths were the end-points. RESULTS: Males were predominant in MI (86%) as compared to AP (77%). Females were predominantly affected by AP (61%, MI 39%), and older than men (61 ± 7 vs 59 ± 8 years, p < 0.001). Coronary stenoses were prevalent in MI. During 115 ± 58 months follow-up, 628 deaths (23%) were observed, including 269 cardiac (43%), and 149 cancer deaths (24%). Long-term prognosis was significantly better in AP than MI group. The lowest prevalence of future MI was recorded in female AP (p < 0.001). CONCLUSIONS: MI as first clinical manifestation of IHD implies a more adverse prognosis than AP; future MI is a rare event in AP; sex influences the first presentation of IHD and its course with possible implications for preventive strategy.

Stress Echocardiography Positivity Predicts Cancer Death.

BACKGROUND: Stress echocardiography (SE) predicts cardiac death, but an increasing share of cardiac patients eventually die of cancer. The aim of the study was to assess whether SE positivity predicts cancer death. METHODS AND RESULTS: In a retrospective analysis of prospectively acquired single-center, observational data, we evaluated 4673 consecutive patients who underwent SE from 1983 to 2009. All patients were cancer-free at index SE and were followed up for a median of 131 months (interquartile range 134). We separately analyzed predetermined end points: cardiovascular, cancer, and noncardiovascular, noncancer death, with and without competing risk. SE was positive in 1757 and negative in 2916 patients; 869 cardiovascular, 418 cancer, and 625 noncardiovascular, noncancer deaths were registered. The 25-year mortality was higher in SE-positive than in SE-negative patients, considering cardiovascular (40% versus 31%; P<0.001) and cancer mortality (26% versus 17%; P<0.01). SE positivity was a strong predictor of cancer (cause-specific hazard ratio 1.19; 95% confidence interval, 1.16-1.73; P=0.05) and cardiovascular mortality (1.18; 95% confidence interval, 1.03-1.35; P=0.02). Fine-Gray analysis to account for competing risk gave similar results. Cancer risk diverged after 15 years, whereas differences were already significant at 5 years for cardiovascular risk. CONCLUSIONS: SE results predict cardiovascular and cancer mortality. SE may act as a proxy of the shared risk factor milieu for cancer or cardiovascular death.

The declining frequency of inducible myocardial ischemia during stress echocardiography over 27 consecutive years (1983-2009).

BACKGROUND: Previous studies have suggested a decline in positivity of stress cardiac imaging, suggesting the need for developing better strategies for test selection to achieve acceptable cost-effectiveness balance. The aim of this retrospective study was to assess the rate of positivity of stress echocardiography (SE) over 27 consecutive years. METHODS: We assessed the rate of SE positivity in 2007 patients without previous myocardial infarction or coronary revascularization who performed SE in a tertiary care referral center from 1983 to 2009. SE was performed with dipyridamole (1427), dobutamine (136) or exercise (444). RESULTS: There was a progressive decline over time in the rate of SE positivity from 42% (1983-1991) to 22% (2001-2009), with a relative increase of patients with low pre-test probability of disease (from 5% to 27%). The percentage of patients studied with SE under anti-ischemic therapy increased markedly (from 8% in the first to 61% in the last nine years). CONCLUSION: Over 27 consecutive years, we observed a steady decline in SE positivity rate (with >5-fold increase of low probability patients), with almost 8-fold increase in anti-ischemic therapy at testing. We probably need refined criteria of referral for testing and/or better ways to titrate the negative response beyond wall motion abnormalities during SE.

Low magnesium is not a significant predictor of hard events in acute myocardial infarction.

BACKGROUND: Although magnesium (Mg) has recognized cardioprotective properties and hypomagnesemia is common in patients with acute myocardial infarction (AMI), data regarding the role of Mg as prognostic factor for adverse events are scarce, as well as there are conflicting results on the use of Mg as adjuvant therapy in AMI. AIM: To evaluate the role of Mg as predictor for hard events (HE, all cause death, and nonfatal myocardial infarction) in AMI patients. DESIGN AND PATIENTS: We studied 406 AMI patients (306 males, age: 67 ± 12 years, mean ± SD). Patient data were collected from the Institute electronic databank which saves demographic, clinical, instrumental, therapeutical and follow-up data of all patients admitted to our Coronary Unit. RESULTS: During a mean follow-up period of 21 ± 18 months, the combined endpoint accounted for 63 HE, 44 (11%) deaths (35 cardiac deaths), 19 (5%) nonfatal MI. The multiple regression model identified glycemia as the only independent determinant of Mg in AMI pts. (T value = - 2.8, standard coefficient = - 0.15, p < 0.01). The Kaplan-Meier survival estimates failed to show a significantly worst outcome in patients presenting low Mg (< 0.783 mmol/L, 25th percentile). Aging (> 67 years-50th percentile), and ejection fraction (< 40%) remained as prognostic factors for HE in the adjusted Cox multivariate proportional hazard model (HR = 2.8, 95% CI = 1.6-5, p < 0.001; HR = 3.2, 95% CI = 1.9-5.3 p < 0.001, respectively). CONCLUSION: The present findings do not support a significant role of low Mg as predictor for HE in AMI.

Gender differences for uric acid as predictor of hard events in patients referred for coronary angiography.

AIM: To assess gender differences in uric acid (UA) as predictor for hard events (HE, mortality and nonfatal myocardial infarction) in a large cohort of patients referred for coronary angiography. Design & patients: 3020 inpatients (2177 males, age: 68 ± 9 years, mean ± SD) were retrospectively studied, collecting data from the Institute electronic databank which included demographic, clinical, instrumental and follow-up data. RESULTS: Although the Kaplan-Meier survival estimates showed a significantly worst outcome in female patients, high UA did not remained a significant predictor for HE after adjustment. Moreover, UA correlated with antioxidant capacity in both sexes. CONCLUSION: Hyperuricemia was not an independent risk for HE, and being correlated with antioxidant capacity, its elevation appears more likely compensatory than causative for HE.

Long-term outcome and medical radiation exposure in patients hospitalized for cardiovascular disease.

BACKGROUND: Low radiation doses from diagnostic and therapeutic procedures may increase cancer incidence after decades in cardiac patients. The aim of the study was to evaluate the long-term outcome and the prognostic effect of radiological exposure. METHODS: A retrospective cohort study examined 16,311 Italian cardiac patients without cancer consecutively hospitalized between 1970 and 2009 and followed-up for a median of 10 years. Cumulative estimated effective dose was calculated for the imaging procedures. Main causes of death and primary cancer onset were the end points and their relation with radiation exposure was analyzed by Cox model. RESULTS: Over the years, there was an increasing trend of cancer, a decreasing trend of cardiovascular, with stability of other-causes death. Cumulative estimated effective radiation dose was higher in patients who died for cancer (20 ± 19 mSv) compared to cardiovascular (17 ± 17, P < 0.001) and other-causes deaths (15 ± 17, p < 0.001). The cumulative estimated effective dose adjusted HR was 1.004 (95% CI 1.000-1.009, p = 0.045) for cancer death and 1.008 (95% CI 1.005-1.011, p < 0.001) for (fatal and non-fatal) cancer onset. Radiation effective dose was not predictive of cardiovascular mortality (HR = 0.991), nor it was of other types of deaths (HR = 0.995). Smoking was a predictor for cardiovascular mortality, but it was not of other types of deaths. CONCLUSIONS: Non-cardiovascular causes of death are responsible for almost half of later deaths in cardiac patients. The radiological exposure from medical imaging procedures is predictive of cancer risk and cancer death.

Inappropriateness of cardiovascular radiological imaging testing; a tertiary care referral center study.

AIMS: Radiological inappropriateness in medical imaging leads to loss of resources and accumulation of avoidable population cancer risk. Aim of the study was to audit the appropriateness rate of different cardiac radiological examinations. METHODS AND PRINCIPAL FINDINGS: With a retrospective, observational study we reviewed clinical records of 818 consecutive patients (67 ± 12 years, 75% males) admitted from January 1-May 31, 2010 to the National Research Council - Tuscany Region Gabriele Monasterio Foundation cardiology division. A total of 940 procedures were audited: 250 chest x-rays (CXR); 240 coronary computed tomographies (CCT); 250 coronary angiographies (CA); 200 percutaneous coronary interventions (PCI). For each test, indications were rated on the basis of guidelines class of recommendation and level of evidence: definitely appropriate (A, including class I, appropriate, and class IIa, probably appropriate), uncertain (U, class IIb, probably inappropriate), or inappropriate (I, class III, definitely inappropriate). Appropriateness was suboptimal for all tests: CXR (A = 48%, U = 10%, I = 42%); CCT (A = 58%, U = 24%, I = 18%); CA (A = 45%, U = 25%, I = 30%); PCI (A = 63%, U = 15%, I = 22%). Top reasons for inappropriateness were: routine on hospital admission (70% of inappropriate CXR); first line application in asymptomatic low-risk patients (42% of CCT) or in patients with unchanged clinical status post-revascularization (20% of CA); PCI in patients either asymptomatic or with miscellaneous symptoms and without inducible ischemia on non-invasive testing (36% of inappropriate PCI). CONCLUSION AND SIGNIFICANCE: Public healthcare system--with universal access paid for with public money--is haemorrhaging significant resources and accumulating avoidable long-term cancer risk with inappropriate cardiovascular imaging prevention.

Colonoscopic surveillance of first-degree relatives of colorectal cancer patients in a faecal occult blood screening programme.

BACKGROUND: In some Italian areas, colonoscopic surveillance of first-degree relatives (FDRs) of colorectal cancer (CRC) patients is provided as a part of local population-based faecal occult blood test (FOBT) screening programmes. The objective of the present study was to assess the feasibility and early results of this surveillance model. METHODS: Data from district screening centres were used to evaluate the process of identification and selection of eligible FDRs (residence in the Emilia-Romagna Region, age 40-75 years, no recent colonoscopy) of screen-detected CRC patients and the detected prevalence of disease. The probability for an FDR to undergo colonoscopy and to be diagnosed with CRC and advanced adenoma was estimated using the Kaplan-Meier method. The sex- and age-standardised ratio of detected prevalence to that expected based on results from a colonoscopy screening study of the Italian general population was estimated. RESULTS: Between 2005 and 2011, 9319 FDRs of 2437 screen-detected CRC patients (3.8 per patient) were identified and contacted. Their likelihood of being eligible for, and accepting, colonoscopy was 0.11 (95% confidence interval: 0.11-0.12). Among the 926 subjects undergoing colonoscopy, the prevalence of previous negative screening FOBT was 63%. Eleven CRCs (1.2%) and 100 advanced adenomas (10.8%) were detected. The standardised ratio of detected prevalence to that expected was 0.91 (95% confidence interval: 0.19-2.66) for CRC and 1.48 (1.04-2.05) for advanced adenoma. CONCLUSIONS: The procedure of selection of FDRs was extremely ineffective. Due to previous negative screening tests, the prevalence of disease was less than expected. A population-based FOBT screening programme is a highly unsuitable setting for the provision of surveillance to FDRs of CRC patients.

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.

High density lipoprotein cholesterol in coronary artery disease: when higher means later.

AIM: Although high-density lipoprotein cholesterol (HDL-C) levels are inversely associated with cardiovascular risk, patients with elevated HDL-C also develop coronary artery disease (CAD) and cardiac events. We aimed to draw the clinical profile of CAD patients with elevated HDL-C and to assess the prognostic impact of elevated HDL-C. METHODS: We prospectively examined 2322 patients (age 67±10 years, 79% male) with chronic CAD, defined by >50% coronary stenosis and/or previous myocardial infarction. RESULTS: HDL-C levels were low (<35 mg/dL) in 736 patients (32%), normal (35-60 mg/dL) in 1464 (63%), and high (>60 mg/dL) in 122 (5%). Patients with elevated HDL-C were less frequently male (p<0.0001), smokers (p<0.0001), diabetic (p<0.0001), and obese (p<0.0015) than those with low or normal HDL-C, but were 3 and 5 years older, respectively (p<0.0001). During follow-up (median, 46 months) 143 patients died from cardiac causes and 80 developed a non-fatal infarction. Cardiac event-free survival was lower in patients with low compared to normal HDL-C (p<0.0001), but was not significantly different from that of patients with elevated HDL-C. The prognostic impact of low HDL-C was independent of age, sex, diabetes, LV function, extent of coronary stenoses, low density lipoprotein cholesterol, triglycerides, complete blood count, thyroid and renal function (p<0.0001). Conversely, the prognostic impact of elevated HDL-C disappeared (p>0.10) after adjustment for age. CONCLUSION: Patients with elevated HDL-C develop CAD and cardiac events as do those with low or normal HDL, but at a more advanced age.