Identification of hemodynamically stable patients with acute pulmonary embolism at high risk for death: external validation of different models.

BACKGROUND: The optimal strategy for identification of hemodynamically stable patients with acute pulmonary embolism (PE) at risk for death and clinical deterioration remains undefined. OBJECTIVES: We aimed at assessing the performances of currently available models/scores for identifying hemodynamically stable patients with acute, symptomatic PE at risk of death and clinical deterioration. METHODS: Prospective multicentre cohort study including patients with acute PE (COPE, NCT03631810). Primary study outcome was in-hospital death within 30 days or clinical deterioration. Other outcomes were in-hospital death, death and PE-related death all at 30 days. We calculated positive and negative predictive values, c-statistics of ESC-2014, ESC-2019, PEITHO, Bova, TELOS, FAST and NEWS2 for the study outcomes. RESULTS: In 5,036 hemodynamically stable patients with acute PE, positive predictive values for the evaluated models/scores were all below 10%, except for TELOS and NEWS2; negative predictive values were above 98% for all the models/scores, except for FAST and NEWS-2. ESC-2014 and TELOS had good performances for in-hospital death or clinical deterioration (c-statistic 0.700 and 0.722, respectively), in-hospital death (c-statistic 0.713 and 0.723, respectively) and PE-related death (c-statistic 0.712 and 0.777, respectively); PEITHO, Bova and NEWS2 also had good performances for PE-related death (c-statistic 0.738, 0.741 and 0.742, respectively). CONCLUSION: In hemodynamically stable patients with acute PE, the accuracy for identification of hemodynamically stable patients at risk for death and clinical deterioration varies across the available models/scores; TELOS seems to have the best performances. These data can inform management studies and clinical practice.

Sudden death in ischemic heart disease: looking for new predictors: polygenic risk.

The phenomenon of sudden death (SD) occurs, in 70% of cases, in people who do not fall within the indications of the guidelines relating to the implantation of the defibrillator. There is a way of inheriting the risk condition by genetic means, the polygenic one, in which mutations are not found, but an increase in alleles of common variations called polymorphisms. The PRE-DETERMINE cohort study has the primary objective of determining whether biological markers, and electrocardiogram can be used to identify individuals more likely to experience SD. Within the study, we investigated the utility of the genome-wide polygenic score for coronary artery disease (GPSCAD) for SD risk stratification in an intermediate-risk population with stable coronary artery disease without severe systolic dysfunction and/or indication for an implantable cardioverter defibrillator in primary prevention. Over a mean follow-up period of 8.0 years, patients in the top decile of GPSCAD were at higher absolute (8.0% vs. 4.8%; P < 0.005) and relative (29% vs. 16%; P < 0.0003) risk of SD compared to the rest of the cohort. No association was found between the highest decile of GPSCAD and other forms of death, cardiac, and non-cardiac. The data on the increase in absolute and relative terms of SD can be used, at this stage, only for a theoretical estimate on the possible efficacy of the defibrillator in the population with chronic coronary artery disease and moderately depressed left ventricular function as number needed to treat and possible reduction of mortality in high-risk patients (those included in the top decile of GPSCAD).

[ANMCO Position paper: Cardiovascular disease in women - prevention, diagnosis, treatment and organization of care]. / Position paper ANMCO: Malattie cardiovascolari nella donna ­ prevenzione, diagnosi, terapia e organizzazione delle cure.

Cardiovascular diseases are still the main cause of death among women despite the improvements in treatment and prognosis achieved in the last 30 years of research. The determinant factors and causes have not been completely identified but the role of "gender" is now recognized. It is well known that women tend to develop cardiovascular disease at an older age than men, and have a high probability of manifesting atypical symptoms not often recognized. Other factors may also co-exist in women, which may favor the onset of specific cardiac diseases such as those with a sex-specific etiology (differential effects of estrogens, pregnancy pathologies, etc.) and those with a different gender expression of specific and prevalent risk factors, inflammatory and autoimmune diseases and cancer. Whether the gender differences observed in cardiovascular outcomes are influenced by real biological differences remains a matter of debate.This ANMCO position paper aims at providing the state of the research on this topic, with particular attention to the diagnostic aspects and to care organization.

Prognostic relevance of Doppler echocardiographic re-assessment in HFrEF patients.

BACKGROUND: Current guidelines do not recommend periodically repeating echocardiograms in the follow-up of stable heart failure patients with reduced ejection fraction (HFrEF). The objective of the study was to verify the additional prognostic information provided by a comprehensive re-assessment of their cardiac function and hemodynamic profile at Doppler echocardiography in HFrEF patients. METHODS: Retrospective analysis of 769 stable HFrEF outpatients who underwent two complete echocardiograms, at baseline and at re-assessment. Main candidate predictors of prognosis were: left ventricular (LV) filling pattern, pulmonary artery systolic pressure (PASP) and right ventricular function (TAPSE). Age, LV ejection fraction, mitral regurgitation severity, NYHA class, brain natriuretic peptide plasma levels at baseline, and their changes at 12 months, were used as covariates. Median follow-up was 30 months. All-cause death was the study end-point. RESULTS: At baseline, restrictive filling pattern and low TAPSE were significant predictors of poor prognosis. At re-evaluation, persistently restrictive/worsened filling pattern, persistently-low/worsened TAPSE and worsened PASP, were associated with poorer survival. A significant interaction between changes in TAPSE, PASP and LV filling pattern was observed: in the restrictive pattern subgroup, survival was poorer in worsened/persistently low TAPSE (p < 0.01); in non-restrictive pattern subgroup, survival was poorer in worsened/persistently elevated PASP (p = 0.01). The re-assessment model improved the C-index from 0.69 to 0.74 (P < 0.01) compared to baseline model. CONCLUSIONS: Doppler echocardiographic re-assessment of LV filling pattern, PASP and TAPSE allows a better prognostic stratification of HFrEF outpatients than baseline evaluation and is additional to changes in BNP and NYHA class.

Similar predictive value of six-minute walking distance and B-type natriuretic peptide in heart failure with reduced to mid-range ejection fraction.

The prognostic insights of heart failure (HF) with mid-range (40-49%) ejection fraction (HFmrEF) are not fully elucidated. We investigated whether the six-minutes walking test (6MWT) and brain natriuretic peptide (BNP) are predictive of outcome across the spectrum of LV systolic dysfunction and whether the HFmrEF cut-off impacts the risk stratification abilities of these tests. We studied 538 outpatients, aged 70±12 years, 28% females, with stable chronic HF and EF<50%, 349 with HFmrEF and 189 with HFrEF. End-points were all-cause and cardiac death. HFrEF patients were more often male, with ischemic etiology, severe symptoms, higher BNP levels, and cardiac mortality than HFmrEF subjects. During 32 (15-46) months follow-up, 123 (23%) patients died, 95 (18%) for cardiac causes. Cut-offs of 125 pg/ml for BNP and 360 meters for 6MWT distance were associated with lower all-cause (10% vs 38%, p<0.001 and 10% vs 26%, p<0.001, respectively) and cardiac mortality (6% vs 36%, p<0.001 and 8% vs 23%, p<0.001, respectively). BNP (HR 2.144, 95%CI, 1.403-3.276) and 6MWT walked distance (HR 1.923, 95%CI, 1.195-3.096) independently predicted outcome, after adjustment for age, gender, obesity, kidney dysfunction, ischemic etiology, NYHA class, unlike the 40% LVEF threshold. Model discrimination and survival differences were significant across LVEF strata. Higher BNP levels and shorter walked distance combined identified patients (26% overall) at particularly poor prognosis in both phenotype groups. Despite differences between HFmrEF and HFrEF patients in clinical and biomarker profile, BNP levels and 6MWT walked distance retain prognostic value over the entire spectrum of LV systolic dysfunction.

Predictive value of interatrial block for atrial fibrillation in elderly subjects enrolled in the PREDICTOR study.

AIMS: The principal aims of this prospective multicentre study were to relate the presence of interatrial block (IAB) with a late occurrence of atrial fibrillation (AF) and to demonstrate the independence of the IAB effect on risk of AF from structural cardiac alterations. METHODS: This prospective study was the follow-up of subjects included in the PREDICTOR cross-sectional population-based study. Subjects were divided into groups according to IAB status. Socio-demographic and health characteristic were collected during enrolment in the PREDICTOR along with ECGs, echocardiograms and NT-proBNP dosages. Follow up was performed on administrative data. The mean time of follow up was 6.6 years. RESULTS: 1626 subjects were included in the analysis. Four hundred-fifteen subjects out of 1626 (25.5%) had IAB. The survival analysis suggests an association between IAB alone and AF (HR = 1.50, p = 0.058) and, in normal-weight subjects, IAB strongly predicted AF indicating more than triple the risk (HR = 3.05; p = 0.002 95% CI: 1.51-6.18). The association seems to be independent of possible confounders such as history of IHD, left ventricular hypertrophy, CHA2DS2-VASc, left atrial dimension, or NT-proBNP dosage. CONCLUSION: Our analysis suggests that IAB is an electric condition that can increase the risk of AF independently of any structural cardiac alterations, at least in normal-weight subjects.

[Peripartum cardiomyopathy: a little known disease]. / La cardiomiopatia peripartum: una malattia poco nota.

Peripartum cardiomyopathy (PPCM) is a relatively rare cardiac disease that manifests itself in the final stage of pregnancy and in the first months after delivery in women with no previous history of cardiovascular disease. The incidence of PPCM varies widely across geographic areas and seems to be on the rise as a result of increased awareness and socioeconomic changes. PPCM recognizes a still partially undefined multifactorial etiology. Various pathogenetic hypotheses have been proposed, that range from autoimmune mechanisms to myocarditis to the hormonal hypothesis for aberrant, antiangiogenic and cardiotoxic prolactin (PRL) production, apoptosis, prolonged exposure to tocolytic drugs, malnutrition and genetic predisposition.The diagnosis of PPCM is still made by exclusion of other etiologies. Although some specific biomarkers with pregnancy-related kinetics have been proposed as diagnostic tools, their value remains questionable and they are not yet available in clinical practice.The prognosis of the disease is variable and not always predictable: both complete functional recovery and poor response to therapy and development of dilated cardiomyopathy and chronic heart failure (HF) may occur, although outcomes appears to have improved slightly in recent years.The acute phase of PPCM may require the use of inotropes and vasodilators as well as mechanical circulatory support and in some cases heart transplant may be indicated. Beta1-adrenergic agonists are contraindicated due to the possible induction of permanent damage due to loss of myocytes, with evolution towards chronic HF. The recent demonstration of the cardiotoxic effect of aberrant PRL has led to successful testing of the therapeutic effects of bromocriptine, a 2D dopamine agonist that blocks PRL. This treatment appears specific to PPCM, as it is targeted at 16k Da PRL, its mediator miR-146a and/or vascular endothelial growth factor.The long-term prognosis, once the acute phase is over, is a function of myocardial damage, and varies from complete functional recovery to chronic HF. Subsequent pregnancies always present a risk of recurrence and hence should be avoided. Even in cases with full functional recovery, relapses in the case of a new pregnancy may occur in 20% of cases. Women who wish a further pregnancy must be adequately informed and, in case of pregnancy, should undergo close monitoring. Treatment of chronic HF does not differ from that from other etiologies, according to international guidelines.

[ANMCO/AICO/AIOM Consensus document: Clinical and management pathways in cardio-oncology]. / Documento di consenso ANMCO/AICO/AIOM: Snodi clinico-gestionali in ambito cardioncologico.

In Italy, cardiovascular diseases and cancer are the leading causes of death. Both diseases share the same risk factors and, having the highest incidence and prevalence in the elderly, they often coexist in the same individual. Furthermore, the enhanced survival of cancer patients registered in the last decades and linked to early diagnosis and improvement of care, not infrequently exposes them to the appearance of ominous cardiovascular complications due to the deleterious effects of cancer treatment on the heart and circulatory system. The above considerations have led to the development of a new branch of clinical cardiology based on the principles of multidisciplinary collaboration between cardiologists and oncologists: Cardio-oncology, which aims to find solutions to the prevention, monitoring, diagnosis and treatment of heart damage induced by cancer care in order to pursue, in the individual patient, the best possible care for cancer while minimizing the risk of cardiac toxicity. In this consensus document we provide practical recommendations on how to assess, monitor, treat and supervise the candidate or patient treated with potentially cardiotoxic cancer therapy in order to treat cancer and protect the heart at all stages of the oncological disease.

Different correlates but similar prognostic implications for right ventricular dysfunction in heart failure patients with reduced or preserved ejection fraction.

AIMS: To evaluate whether the clinical and echocardiographic correlates and the prognostic significance of right ventricular (RV) dysfunction are different in heart failure patients with reduced (HFrEF), mid-range (HFmrEF), or preserved (HFpEF) left ventricular ejection fraction. METHODS AND RESULTS: The study included 1663 patients with heart failure caused by ischaemic or hypertensive heart disease or by idiopathic cardiomyopathy. Left ventricular ejection fraction was <40% in 1123 patients (HFrEF), 40-49% in 156 patients (HFmrEF) and ≥50% in 384 patients (HFpEF). Imaging of the right ventricle was performed by echocardiography; RV function was defined on the basis of tricuspid annular plane systolic excursion (TAPSE) and its normalization for pulmonary artery systolic pressure (PASP). All-cause mortality was the endpoint of survival analysis. Non-sinus rhythm, high heart rate, ischaemic aetiology and E-wave deceleration time <140 ms were associated with a reduced TAPSE in HFrEF patients, whereas PASP >40 mmHg was by far the strongest correlate of a reduced TAPSE in HFpEF and HFmrEF patients (interaction analysis, P = 0.0011). TAPSE/PASP proved to be a powerful predictor of prognosis in all patients. CONCLUSIONS: The correlates of RV dysfunction differ in HFrEF compared with HFpEF and HFmrEF patients. Regardless of the extent of LV dysfunction, the TAPSE/PASP ratio is a powerful independent predictor of prognosis in all heart failure patients.

Clinical presentation and in-hospital death in acute pulmonary embolism: does cancer matter?

Cancer is one of the most common risk factors for acute pulmonary embolism (PE), but only few studies report on the short-term outcome of patients with PE and a history of cancer. The aim of the study was to assess whether a cancer diagnosis affects the clinical presentation and short-term outcome in patients hospitalized for PE who were included in the Italian Pulmonary Embolism Registry. All-cause and PE-related in-hospital deaths were also analyzed. Out of 1702 patients, 451 (26.5 %) of patients had a diagnosis of cancer: cancer was known at presentation in 365, or diagnosed during the hospital stay for PE in 86 (19 % of cancer patients). Patients with and without cancer were similar concerning clinical status at presentation. Patients with cancer less commonly received thrombolytic therapy, and more often had an inferior vena cava filter inserted. Major or intracranial bleeding was not different between groups. In-hospital all-cause death occurred in 8.4 and 5.9 % of patients with and without cancer, respectively. At multivariate analysis, cancer (OR 2.24, 95 % CI 1.27-3.98; P = 0.006) was an independent predictor of in-hospital death. Clinical instability, PE recurrence, age ≥75 years, recent bed rest ≥3 days, but not cancer, were independent predictors of in-hospital death due to PE. Cancer seems a weaker predictor of all-cause in-hospital death compared to other factors; the mere presence of cancer, without other risk factors, leads to a probability of early death of 2 %. In patients with acute PE, cancer increases the probability of in-hospital all-cause death, but does not seem to affect the clinical presentation or the risk of in-hospital PE-related death.

Evaluation of different strategies for identifying asymptomatic left ventricular dysfunction and pre-clinical (stage B) heart failure in the elderly. Results from 'PREDICTOR', a population based-study in central Italy.

AIMS: To evaluate the accuracy and cost-effectiveness of different screening strategies to identify systolic and/or diastolic asymptomatic LV dysfunction (ALVD), as well as pre-clinical (stage B) heart failure (HF), in a community of elderly subjects in Italy. METHODS AND RESULTS: A sample of 1452 subjects aged 65-84 years were chosen from the original cohort of 2001 randomly selected residents of the Lazio Region (Italy), as a part of the PREDICTOR survey. All subjects underwent physical examination, biochemistry/NT-proBNP assessment, 12-lead ECG, and Doppler transthoracic echocardiography (TE). Five strategies were evaluated including ECG, NT-proBNP, TE, and their combinations. Subjects older than 75 years, and with at least two additional risk factors, were defined as being high-risk for HF (435), whereas the remaining 1017 were defined at low risk. Screening characteristics and cost-effectiveness (cost per case) of the five strategies to predict systolic (EF <50% ) or diastolic ALVD and pre-clinical HF (stage B) were compared. NT-proBNP was the most accurate and cost-effective screening strategy to identify systolic and moderate to severe diastolic LV dysfunction without a difference between the high-risk and low-risk groups. Adding ECG to the NT-proBNP assessment did not improve the detection of pre-clinical LV dysfunction. TE-based screening was the least cost-effective strategy. In fact, all screening strategies were inadequate to identify stage B HF. CONCLUSIONS: In a community of elderly people, NT-proBNP is the most accurate and cost- effective pre-screening strategy to identify systolic and moderate to severe diastolic LV dysfunction.

[The Italian Network for Heart Failure five years after the publication of the Italian "Consensus conference on the management of heart failure"]. / La rete per io Scompenso Cardiaco in Italia cinque anni dopo la pubblicazione della Consensus Conference "Il percorso assistenziale del paziente con Scompenso Cardiaco": a che punto siamo?

In the year 2006 the Italian Association of Hospital Cardiologists (ANMCO) promoted a Consensus Conference among professional Scientific Societies in order to redefine the role and core responsibilities of each health professionals involved in heart failure management in a novel integrated network. Five years later, a questionnaire has been proposed to each Italian Regional President of the Association, in order to assess the implementation of the proposed management strategies in the different clinical scenarios of the Italian Regions. Although the Document utilization is not homogeneous through Italy, it is still considered a valuable tool of work.

A case for assessment of oscillatory breathing during cardiopulmonary exercise test in risk stratification of elderly patients with chronic heart failure.

UNLABELLED: The prognostic value of exercise oscillatory breathing (EOB) during cardiopulmonary test (CPX) has been described in young chronic heart failure (HF) patients. We assessed the prognostic role of EOB vs other clinical and ventilatory parameters in elderly HF patients performing a maximal CPX. METHODS AND RESULTS: We prospectively followed-up 370 HF outpatients ≥ 65 years after a symptom limited CPX. We tested the predictive value of clinical and ventilatory parameters for all-cause mortality and a composite of all-cause mortality and HF hospitalizations. Median age was 74 years, 51% had ischemic heart disease, 25% NYHA class III; ejection fraction was 41% [34-50]. Peak oxygen consumption (PVO(2)) was 11.9 [9.9-14] mL/kg/min, the slope of the regression line relating ventilation to CO(2) output, (VE/VCO(2) slope) was 33.9 [29.8-39.2]. EOB was found in 58% of patients. At follow-up, 84 patients died and overall 158, using a time-to-first event approach, met the composite end-point. Independent predictors of all-cause mortality were CPX EOB and the ratio of VE/VCO(2) slope to peak VO(2), hemoglobin, creatinine and body mass index. The area under the ROC curve (AUC) of the Cox multivariable model was 0.80 (95% CI 0.73 to 0.87). Independent predictors of the composite end-point were EOB, VE/VCO(2) slope, hemoglobin and HF admissions in the previous year (Model AUC 0.75) (95% CI 0.69 to 0.81). CONCLUSIONS: Among elderly HF patients, EOB prevalence is higher than middle-aged cohorts. EOB and the ratio of VE/VCO(2) slope to peak VO(2) resulted the strongest ventilatory predictor of all-cause mortality, independent of ventricular function.

[Heart failure phenotype in women]. / Caratteristiche fenotipiche e strutturali dello scompenso cardiaco nella donna.

Although one half of patients affected by heart failure (HF) are women, the clinical phenotype differs between genders. In women HF develops later in life, is more often associated with preserved systolic function and is less frequently attributable to ischemic heart disease. Although survival tends to be better in women than in men, females are more symptomatic, have a worse quality of life and a longer length of stay during acute HF admissions. Italian data from institutional databases of the Lazio, Basilicata and Veneto regions are in agreement with international evidences on this topic. Gender differences in clinical phenotypes are based on different structural and functional patterns: the female heart undergoes more often concentric remodeling, with thicker walls, smaller volumes and greater chamber stiffness. There are no specific therapeutic evidences for the elderly, prevalently female, HF population. Treatment strategies are derived from studies carried out in relatively young male populations with left ventricular systolic dysfunction. Therapeutic strategies tailored to the peculiar female HF phenotype should be better explored in future treatment trials.

[Role of clinical evaluation and functional testing in the tailored follow-up of chronic heart failure patients]. / Ruolo della valutazione clinica e dei test funzionali per la personalizzazione del follow-up nel paziente con scompenso cardiaco cronico.

Clinical assessment is crucial to monitor chronic heart failure (HF) patients. It allows to tailor follow-up based on clinical severity, symptoms, quality of life and life expectancy. Risk scores, a useful tool for synthetic assessment of patients and intercenter standardization, should be easy to calculate and consider both cardiac conditions and comorbidities. In the elderly, clinical assessment should include indexes of disability and frailty, mandatory to tailor follow-up appropriately. Clinical data should be complemented by objective measures of functional capacity using exercise testing. Exercise tolerance, a comprehensive index of body function, is a pivotal prognostic predictor. The 6-min walking test is simple, well accepted by patients, and provides an objective documentation of exercise tolerance in subjects who cannot perform a maximal stress test. However, there is no evidence to support its role for risk stratification. While the cardiopulmonary exercise test has a definite role in the selection of heart transplant candidates, it also provides important information for risk stratification of the general HF population, the main prognostic predictors being maximal oxygen consumption, periodic breathing, and an enhanced ventilatory response to exercise.

Oxygen pulse as a predictor of cardiopulmonary events in lung resection.

Traditional algorithms suggest a stepwise approach to the functional evaluation of candidates for lung resection. A cardiopulmonary exercise test is incorporated as a supplementary test for patients with borderline pulmonary predicted values, and sometimes as a first screening test for cardiac risk evaluation. To assess the predictive weight of exercise tests in noncardiac thoracic surgery, we retrospectively analyzed 99 patients (80 males) aged 67.8 +/-8.1 years who underwent lung resection after a cardiopulmonary exercise test. During basal spirometry, the mean predicted forced expiratory volume in the first second was 69.9% +/-18.6%, and predicted carbon monoxide diffusing capacity was 71.6% +/-20.5%. Peak oxygen consumption was 11.1 +/-3.2 mL.kg(-1).min(-1), oxygen pulse was 9 +/-2.8 mL.beat(-1), and minute ventilation/CO(2) output was 45.2 +/- 7.7. Mean hospital stay was 10.4 days, and intensive care unit stay was 0.3 days. Postoperative complications occurred in 20 (20%) patients. On multivariate analysis, body mass index, a high level of exercise achieved during the cardiopulmonary exercise test, lower heart rate at peak exercise, and oxygen pulse correlated significantly with better postoperative outcome. Cardiopulmonary exercise tests are helpful for stratifying patients undergoing thoracic surgery. Perioperative complications seem to be strongly related to left ventricular function and physical performance.

Prognostic value of brain natriuretic peptide and enhanced ventilatory response to exercise in patients with chronic heart failure.

Whether brain natriuretic peptide (BNP), combined with a cardiopulmonary exercise test (CPx) parameters or echocardiography improves prognostic stratification in mild-to-moderate systolic heart failure (HF) is currently unclear. In 156 consecutive stable outpatients with mild to moderate HF and left ventricular ejection fraction (LVEF) <40%, we assessed the impact of BNP assay, Doppler echocardiography and CPx on survival. Median BNP plasma levels were 207 [90-520] pg/mL. Mean LVEF was 33 +/- 7%. Left bundle branch block (LBBB) was present in 52 patients (33%) and a restrictive filling pattern in 35 (22%). The slope of the relation between minute ventilation and carbon dioxide production (VE/VCO(2) slope) averaged 35 +/- 8; an enhanced ventilatory response (EVR) to exercise (VE/VCO(2) slope >35) was found in 67 patients (43%). During 759 +/- 346 days of follow-up, 24 patients died. By multivariate analysis, the strongest independent predictors of all-cause death among clinical, echocardiographic variables and BNP were LBBB and beta-blocker treatment. When CPx variables were added, the best predictors of mortality were LBBB, beta-blockade and VE/VCO(2) slope. This study highlights the value of a sequential approach, based on clinical, laboratory and functional data to identify high-risk HF patients. BNP assay might constitute a simple alternative tool for patients with an inability or with clinical contraindications to exercise, advanced physical deconditioning and unreliable CPx results. However, whenever feasible, CPx with assessment of EVR is recommended for a more accurate prediction of prognosis.