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.

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.

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.

Prevalence of thyroid dysfunction and effect of contrast medium on thyroid metabolism in cardiac patients undergoing coronary angiography.

BACKGROUND: Iodinated contrast media (CM) may influence thyroid function. Precautions are generally taken in patients with hyperthyroidism, even if subclinical, whereas the risks in patients with hypothyroidism or low triiodothyronine (T3) syndrome are not considered as appreciable. PURPOSE: To assess the presence and type of thyroid dysfunction in patients admitted for coronary angiography (CA), to assess the concentration of free-iodide in five non-ionic CM, and to evaluate changes in thyroid function after CA in patients with low T3 syndrome. MATERIAL AND METHODS: We measured free T3, free thyroxine (T4), and thyroid-stimulating hormone (TSH) in 1752 consecutive patients prior to CA and free-iodide in five non-ionic CM. Urinary free-iodide before and 24 h after CA, and thyroid hormone profile 48 h after CA were also made in 17 patients with low T3 syndrome. Patients were followed up for an average duration of 63.5 months. RESULTS: The patients were divided into four groups: euthyroidism (60%), low T3 syndrome (28%), hypothyroidism (10%), and hyperthyroidism (2%). The free-iodide resulted far below the recommended limit of 50 µg/mL in all tested CM. In low T3 syndrome, 24-h free-iodide increased after CA from 99.9 ± 63 ug to 12276 ± 9285 ug (P < 0.0001). A reduction in TSH (4.97 ± 1.1 vs. 4.17 ± 1.1 mUI/mL, P < 0.01) and free T3 (1.44 ± 0.2 vs. 1.25 ± 0.3 pg/mL, P < 0.01), with an increase in free T4 (11.3 ± 2.9 vs. 12.5 ± 3.4 pg/dL, P < 0.001), was found. Patients with functional thyroid disease in the follow-up had a significant lower rate survival compared to euthyroid patients (90.7 vs. 82.2%, P < 0.00001). CONCLUSION: Thyroid dysfunction is frequent in patients who perform a CA, and low T3 syndrome is the predominant feature. The administration of contrast medium may further compromise the thyroid function.

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.

Oxidative stress as a predictor of cardiovascular events in coronary artery disease patients.

BACKGROUND: Enhanced oxidative stress has been associated with atherosclerosis and coronary artery disease (CAD). However, the predictive value of circulating oxidative stress biomarkers for cardiovascular events (CE) in patients with CAD has remained poorly understood. AIM: To assess the prognostic significance of reactive oxygen metabolites, estimated as index of oxidative stress in serum samples by means of a commercial kit (ROMs, Diacron, Italy) on the rate of mortality and major adverse CE (MACE) in CAD. METHODS: A study of 93 consecutive patients with angiographically documented CAD (75 males, age: 68±10 years, mean±SD) was made during a mean follow-up of 66 months until the occurrence of one of the following CE: cardiac and all cause death, non-fatal myocardial infarction and coronary revascularization [percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG)]. Patient data were retrospectively collected from the Institute's electronic databank that saves demographic, clinical, instrumental and follow-up data of all patients admitted to our department. RESULTS: The Kaplan-Meier survival estimates showed a significantly worst outcome in patients presenting elevated ROM level (>75th percentile, corresponding to 481 AU) (log rank=11, 7.5, 5.1; p<0.001, p<0.01, p<0.05 for cardiac and all cause death and MACEs, respectively). In a multivariate Cox regression model, elevated oxidative stress remained a significant predictor of cardiac and all cause death [hazard ratio (HR) 3.9, 95% confidence interval, 95% (CI) 1.4-11.1, p=0.01; HR=2.6, 95% CI 1.1-6.2, p=0.02) and MACE (HR=1.8, 95% CI 1.1-3.1, p=0.03)]. CONCLUSIONS: The estimation of ROMs may represent an additional prognostic tool in the assessment of CE in CAD patients.

Prognostic implication of stress echocardiography in 6214 hypertensive and 5328 normotensive patients.

Aims To compare the prognostic implication of stress echocardiography (SE) in a large cohort of hypertensive and normotensive patients with known or suspected coronary artery disease (CAD). The relative prognostic meaning of the SE result in hypertensive and normotensive patients remains to be addressed. Methods and results The study group was formed by 11 542 patients (6214 hypertensive patients; 5328 normotensive patients) who underwent exercise (n= 686), dobutamine (n= 2524), or dipyridamole (n= 8332) SE for evaluation of known (n= 4563) or suspected (n= 6979) CAD. Patients were followed up for a median of 25 months (1st quartile, 7; 3rd quartile, 57). Ischaemia on SE (new wall motion abnormality) was detected in 3209 (28%) patients. During follow-up, 1587 events (924 deaths, 663 non-fatal infarctions) occurred. Patients (n= 2764) undergoing revascularization were censored. The annual event rate was 7.0% in hypertensive and 5.7% in normotensive patients (P = 0.02) with known CAD, and 3.7% in hypertensive and 2.4% in normotensive patients (P< 0.0001) with suspected CAD. Ischaemia on stress echo, resting wall motion abnormality (RWMA), age, male sex, and diabetes mellitus were multivariable prognostic predictors in both patient groups. Analysing data according to the interaction of prognostically important echocardiographic covariates, such as ischaemia on SE and RWMA, an effective risk assessment was obtained in hypertensive as well as normotensive patients. The annual event rate was markedly higher in hypertensive than in normotensive patients with no ischaemia and no RWMA (2.5 and 1.7%, P = 0.0001). Finally, the incremental prognostic value of inducible ischaemia over clinical evaluation and resting left ventricular function was greater in hypertensive than in normotensive patients both with known and suspected CAD. Conclusion The SE result allows an effective prognostication in hypertensive and normotensive patients. However, a non-ischaemic test predicts better survival in normotensive than in hypertensive patients with no RWMA.

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.

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.

Through-the-scope large diameter self-expanding metal stent placement as a safe and effective technique for palliation of malignant colorectal obstruction: a single center experience with a long-term follow-up.

OBJECTIVE: The aim of this study was to evaluate the outcomes of through-the-scope (TTS) large diameter self-expanding metal stent (SEMS) placement for palliation of malignant colorectal obstruction. MATERIAL AND METHODS: Between January 2005 and December 2009, all patients who underwent endoscopic SEMS placement for palliation of malignant colorectal obstruction were prospectively enrolled. RESULTS: Thirty-nine patients (17M and 22F; mean age 75.9 ± 10.6 years, range 50-91) were enrolled. The most frequent location was the sigmoid colon (13 cases). The causes of obstruction were colorectal malignancy in 32 patients and extracolonic malignancy in 7. Technical success was achieved in 36/39 patients (92.3%) and clinical success in 35/39 patients (89.7%). Technical failure was related to female sex (p = 0.04) and the extracolonic etiology of the stricture (p < 0.001). There were three early complications: two procedure-related perforations successfully managed conservatively and one hemorrhage treated with APC. Early complications were related to the location of strictures at the recto-sigmoid junction (p < 0.001). Late complications occurred in 10 patients: 8 of these patients experienced occlusive symptoms (attributable to tumor ingrowth in 5 cases and stool impaction in 3 cases); the remaining 2 were one case of tumor ingrowth with sub-occlusive symptoms and hemorrhage, and one case of distal migration. There was no procedure-related mortality and all complications were managed without surgical intervention. SEMS patency duration was 236 ± 128 days (range 31-497) and mean survival of the patients was 259 ± 121 days (range, 32-511). CONCLUSIONS: In our experience, TTS large-diameter SEMS placement is a safe and effective treatment for palliation of malignant colorectal obstruction.

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.

Efficacy, safety and outcomes of 'inject and cut' endoscopic mucosal resection for large sessile and flat colorectal polyps.

BACKGROUND AND STUDY AIMS: The study examines the outcomes of the 'inject and cut' endoscopic mucosal resection (EMR), for large sessile and flat colorectal polyps. PATIENTS AND METHODS: Between January 2006 and December 2008 all patients referred to our institution for EMR of large polyps were prospectively evaluated. The accuracy of lifting sign and the rate of en bloc and piecemeal resection, complications and recurrence were analyzed. RESULTS: A total of 157 patients with 182 lesions (median size 24.7 +/- 10.2 mm) were included in the study. The most frequent location was the sigmoid colon in 30.2%. Because of non-lifting sign, 5/182 lesions were referred to surgical resection and 177 (43 flat and 134 sessile) were resected, 79 (44.6%) en bloc and 98 (55.4%) piecemeal. There were 20 procedural (11.3%) and 2 late (1.1%) bleeding, 4 post-polypectomy syndrome (2.2%) and 2 perforations (1.1%). Bleeding was related to malignancy (p = 0.01). Intramucosal cancer was observed in 5 cases (2.8%) while invasive cancer was seen in 8 (4.5%). Malignancy was related to polyp size >or=30 mm (p = 0.002). Follow-up colonoscopy was performed in 147 patients with 172 EMR for a mean of 19.8 months. Recurrence was observed in 12/172 (6.9%) polyps. CONCLUSION: Inject and cut EMR is practical and effective with a low risk of complication and local recurrence.

Endoclip-assisted resection of large pedunculated colorectal polyps: technical aspects and outcome.

BACKGROUND: The most common complication of polypectomy is hemorrhage, and various techniques have been used to prevent this complication. AIM: This study evaluates the outcomes of endoclip-assisted polypectomy in patients with large pedunculated colorectal polyps, in comparison with a historical control group of patients treated with endoloop-assisted polypectomy. METHODS: Between January and December 2007, 32 patients with 32 large pedunculated polyps (>or=15 mm) were treated with endoclip-assisted polypectomy (group A). Between January and December 2006, 35 patients with 35 large pedunculated polyps were treated; 33 with endoloop-assisted polypectomy (control, group B) and two cases with endoclips and needle knife, which were included in group A for the analysis. RESULTS: The mean (+/- standard deviation [SD]) size of polyp head was 26.8 +/- 8.1 mm (range 15-50) in group A and 22.3 +/- 4.1 mm (range 15-30) in group B (P = 0.004). In group A, six polyps had a mean (+/-SD) head size of 40.8 +/- 5.8 mm (range 35-50) and were resected with clips and needle knife. In group A, bleeding occurred in two cases (5.9%), which were associated with the presence of cancer at histology (P = 0.006) and were managed by applying new clips. No bleeding occurred in patients of group B and no perforation and post-polypectomy syndrome occurred in either group. There were three (8.8%) cancerized adenomas in group A and one (3%) in group B. Clip application was possible in all patients, while in two cases, loop placement was impossible. CONCLUSIONS: In our experience, endoclip-assisted resection is a safe alternative to endoloop for the resection of large pedunculated colorectal polyps when endoloop placement is difficult or impossible.

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.

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.

Stress/Rest Myocardial Perfusion Abnormalities by Gated SPECT: Still the Best Predictor of Cardiac Events in Stable Ischemic Heart Disease.

UNLABELLED: The prognostic power of myocardial perfusion imaging in patients with ischemic heart disease (IHD) has been demonstrated since planar imaging. We aimed to investigate whether gated SPECT retains this value in current cardiology if compared with a complete diagnostic work-up and with more recent prognostic indicators. METHODS: We selected from our database a cohort of 676 consecutive inpatients who underwent a complete diagnostic work-up that included gated SPECT and coronary arteriography for known or suspected IHD. Patients with acute myocardial infarction (MI), previous coronary artery bypass surgery, or overt hyperthyroidism and patients who were undergoing dialysis treatment were excluded. During follow-up (median, 37 mo), 24 patients died from cardiac causes and 19 experienced a nonfatal MI. RESULTS: The following were determined to be independent predictors of event-free survival (cardiac death and nonfatal MI) in the different phases of diagnostic work-up using Cox proportional hazards regression analysis: among clinical variables, a previous MI; among laboratory examinations, serum creatinine and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels; among electrocardiographic and echocardiographic variables, left ventricular ejection fraction; and among SPECT variables, summed rest score (SRS) and summed difference score (SDS). In addition, a score of coronary stenoses at angiography was an independent predictor. When the above predictors were tested together, SRS (P < 0.0001), SDS (P = 0.0108), and serum creatinine (P = 0.0186) and LDL and HDL cholesterol levels (P = 0.0222) were the final independent predictors of event-free survival. When gated SPECT was added to the clinical, laboratory, electrocardiographic, and echocardiographic variables, the prognostic stratification significantly improved (P < 0.05); when coronary arteriography was added to gated SPECT, prognostic stratification did not further improve (P > 0.25). If the information provided by gated SPECT was made available after clinical, laboratory, electrocardiographic, echocardiographic, and angiographic variables, the prognostic stratification still improved significantly (P < 0.05). In 492 of these patients with ascertained IHD, SRS and SDS were the final independent predictors of survival. Medical treatment and coronary revascularization did not affect the prognostic information of gated SPECT. CONCLUSION: Myocardial perfusion abnormalities at rest and after stress are still the best predictors of cardiac event-free survival in patients with known or suspected IHD, even when compared with an extensive diagnostic work-up.

Prognostic value of combined measurement of brain natriuretic peptide and triiodothyronine in heart failure.

BACKGROUND: Both low free triiodothyronine (fT3) and high brain natriuretic peptide (BNP) have been separately described as prognostic predictors for mortality in heart failure (HF). We investigated whether their prognostic value is independent. METHODS AND RESULTS: From January of 2001 to December of 2006, we prospectively evaluated 442 consecutive patients with systolic HF and no thyroid disease or treatment with drugs affecting thyroid function (age 65+/-12 years, mean +/- standard deviation, 75% were male, left ventricular ejection fraction 33% +/- 10%, New York Heart Association (NYHA) class I and II: 63%, NYHA class III and IV: 37%). All patients underwent full clinical and echocardiographic evaluation and assessment of BNP and thyroid function. Both cardiac and all-cause mortality (cumulative) were considered as end points. During a median 36-month follow-up (range 1-86 months), 110 patients (24.8%) died, 64 (14.4%) of cardiac causes. Univariate Cox model predictors of all-cause mortality and cardiac death were age, body mass index, creatinine, hemoglobin, ejection fraction, NYHA class, BNP, fT3, and thyroxine level. Multivariate analysis selected age, NYHA class, hemoglobin, BNP, and fT3 as independent predictors for all-cause mortality and NYHA class, BNP, and fT3 as independent predictors for cardiac mortality. Patients with low fT3 and higher BNP showed the highest risk of all-cause and cardiac death (odds ratio 11.6, confidence interval, 5.8-22.9; odds ratio 13.8, confidence interval, 5.4-35.2, respectively, compared with patients with normal fT3 and low BNP). CONCLUSION: fT3 and BNP hold an independent and additive prognostic value in HF.

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.