Acute pulmonary embolism and cancer: findings from the COPE study.

BACKGROUND: Patients with acute venous thromboembolism associated with cancer have an increased risk of recurrences and bleeding in the long term. RESEARCH QUESTION: To describe the clinical features and short-term course of patients with acute pulmonary embolism (PE) and active cancer, previous cancer or no cancer. STUDY DESIGN AND METHODS: Patients with acute PE included in COPE-prospective, multicentre study of adult patients with acute, symptomatic, objectively diagnosed PE-were classified as having active cancer, previous cancer, or no cancer. RESULTS: Overall, 832 patients had active cancer, 464 with previous cancer and 3660 patients had no cancer at the time of acute PE. The most prevalent primary sites of active cancer were urogenital (23.0%), gastrointestinal (21.0%), and lung (19.8%), with a high prevalence of metastatic disease (57.6%) and ongoing anticancer treatment (16.2%). At discharge, a direct oral anticoagulant was used in 43.1%, 78.8%, and 82.0% of patients with active cancer, previous cancer, and no cancer, respectively. Rates of death in-hospital and at 30 days were higher in patients with active cancer compared to patients with previous cancer and no cancer (7.9% vs. 4.3% vs. 2.2% and 13.8% vs. 5.2% vs. 2.6%, respectively). Rates of major bleeding were 4.8%, 2.6%, and 2.4%, respectively. Among patients with active cancer, lung or metastatic cancer were independent predictors of death; brain, hematological or gastrointestinal cancer had the highest risk of major bleeding. INTERPRETATION: Among patients with acute PE, those with active cancer have high risks for death or major bleeding within 30 days. These risks vary based on primary site of cancer. CLINICAL TRIAL REGISTRATION: clinicaltrial.gov identifier: NCT03631810.

Rationale and design of the Biventricular Evaluation of Gliflozins effects In chroNic Heart Failure: BEGIN-HF study.

AIMS: Sodium-glucose cotransporter type 2 inhibitors (SGLT-2i) represent a unique class of anti-hyperglycaemic agents for type 2 diabetes mellitus that selectively inhibit renal glucose reabsorption, thereby increasing urinary excretion of glucose. Several studies have demonstrated the cardioprotective effects of SGLT-2i in patients with heart failure (HF), unrelated to its glucosuric effect. It is unclear whether the benefits of SGLT-2i therapy also rely on the improvement of left ventricular (LV) and/or right ventricular (RV) function in patients with HF. This study aimed to evaluate the effect of SGLT-2i on LV and RV function through conventional and advanced echocardiographic parameters with a special focus on RV function in patients with HF. METHODS AND RESULTS: The Biventricular Evaluation of Gliflozins effects In chroNic Heart Failure (BEGIN-HF) study is an international multicentre, prospective study that will evaluate the effect of SGLT-2i on echocardiographic parameters of myocardial function in patients with chronic stable HF across the left ventricular ejection fraction (LVEF) spectrum. Patients with New York Heart Association Class II/III symptoms, estimated glomerular filtration rate > 25 mL/min/1.73 m2 , age > 18 years, and those who were not previously treated with SGLT-2i will be included. All patients will undergo conventional, tissue-derived imaging (TDI), and strain echocardiography in an ambulatory setting, at time of enrolment and after 6 months of SGLT-2i therapy. The primary endpoint is the change in LV function as assessed by conventional, TDI, and myocardial deformation speckle tracking parameters. Secondary outcomes include changes in RV and left atrial function as assessed by conventional and deformation speckle tracking echocardiography. Univariate and multivariate analyses will be performed to identify predictors associated with primary and secondary endpoints. CONCLUSIONS: The BEGIN-HF will determine whether SGLT-2i therapy improves LV and/or RV function by conventional and advanced echocardiography in patients with HF irrespective of LVEF.

[Caseous calcification of the mitral annulus: case report and review of the literature]. / Calcificazione caseosa dell'anulus mitralico: caso clinico e revisione della letteratura.

Caseous calcification of the mitral annulus is an uncommon variant of mitral annular calcification. It appears as a round echodense mass containing central areas of echolucencies resembling liquefaction and with no flow in the central zone on color Doppler. In most cases it involves the posterior mitral annulus region, particularly in female subjects. The pathogenesis remains unclear: hypercholesterolemia and the dissolution of lipid-rich macrophages may be implicated in liquefaction necrosis. Transthoracic and transesophageal echocardiography represents the most reliable technique for diagnosis, whereas cardiac magnetic resonance imaging is the choice in doubtful cases. We report the case of an 82-year-old female patient describing different aspects of this particular clinical condition.

Paradigm shift in heart failure treatment: are cardiologists ready to use gliflozins?

Despite recent advances in chronic heart failure (HF) therapy, the prognosis of HF patients remains poor, with high rates of HF rehospitalizations and death in the early months after discharge. This emphasizes the need for incorporating novel HF drugs, beyond the current approach (that of modulating the neurohumoral response). Recently, new antidiabetic oral medications (sodium-glucose cotransporter 2 inhibitors (SGLT2i)) have been shown to improve prognosis in diabetic patients with previous cardiovascular (CV) events or high CV risk profile. Data from DAPA-HF study showed that dapaglifozin is associated with a significant reduction in mortality and HF hospitalization as compared with placebo regardless of diabetes status. Recently, results from EMPEROR-Reduced HF trial were consistent with DAPA-HF trial findings, showing significant beneficial effect associated with empagliflozin use in a high-risk HF population with markedly reduced ejection fraction. Results from the HF with preserved ejection fraction trials using these same agents are eagerly awaited. This review summarizes the evidence for the use of gliflozins in HF treatment.

Proprotein convertase subtilisin/kexin type 9 inhibitors treatment in dyslipidemic patients: a real world prescription.

AIM: Dyslipidemia is recognized as one of the major risk factors for cardiovascular diseases. This retrospective observational study was aimed to assess the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in dyslipidemic patients with a lipid profile not well controlled by maximally tolerated statin therapy or intolerant to these lipid-lowering drugs. We enrolled 151 patients, of whom, 119 were taking evolocumab and 32 alirocumab. RESULTS: Total cholesterol significantly decreased progressively until the fourth year; after 4 years there was a significant reduction (-125.5 mg/dl, -51.5%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year and P < 0.05 vs 2 years) and -2.8 mg/dl (-2.3%) compared with the third year. Low-density lipoprotein-cholesterol (LDL-C) also decreased significantly until the fourth year. After 3 years, there was a significant reduction (-117.8 mg/dl, -71.5%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year) and -13.9 mg/dl (-22.8%) compared with the second year; after 4 years there was a significant reduction (-121.4 mg/dl, -73.7%, P < 0.0001 vs baseline, and P < 0.05 vs 1 year and P < 0.05 vs 2 years) and -3.6 mg/dl (-7.7%) compared with the third year. High-density lipoprotein-cholesterol increased significantly only during the fourth year of detection. After 3 years, there was a nonsignificant increase (4.9 mg/dl, 10.0%, P = 0.061 vs baseline) and 1.6 mg/dl (3.1%) compared with the second year; after 4 years, there was a significant increase (5.2 mg/dl, 10.6%, P < 0.05 vs baseline) and 0.3 mg/dl (0.6%) compared with the third year. The value of Tg was significantly reduced progressively until the second year and then stabilized in the third and fourth years. After 3 years, the value of Tg stabilized (-48.6 mg/dl, -32.4%, P < 0.01 vs baseline, and P < 0.05 vs 1 year) and -4.8 mg/dl (-4.5%) compared with the second year; after 4 years (-46.4 mg/dl, -31.0%, P < 0.01 vs baseline, and P < 0.05 vs 1 year) there was a slight and nonsignificant increase of 2.2 mg/dl (2.2%) compared with the third year. Regarding adverse events, both drugs were well tolerated. CONCLUSIONS: We showed that PCSK9 inhibitors are well tolerated and provide long-term significant LDL-C lowering in individuals with hyperlipidemia.

Acute heart failure due to COVID-19 related myocardial injury and de novo hypertensive cardiomyopathy: a challenging diagnosis.

We report a COVID-19 case with acute heart and kidney failure in a healthy young male. Echocardiography showed severe systolic and diastolic left ventricle dysfunction, with diffuse myocardial thickening. Cardiac MRI showed aspects of focal myocarditis, and hypertensive cardiomyopathy. Renal biopsy demonstrated limited acute tubular injury, and hypertensive kidney disease. Coronary angiography excluded critical stenoses. Unlike what we initially suspected, myocardial inflammation had a limited extent in our patient; severe hypertension causing cardiomyopathy and multi-organ damage, not diagnosed before, was primarily responsible for severe illness. Correct diagnosis and guidelines-directed treatment allowed a favorable course.

Severe Aortic Regurgitation of Early Degenerated Mitroflow Bioprosthesis: From Echocardiographic Diagnosis to Treatment with Valve-in-Valve Transcatheter Aortic Valve Implantation.

Valve-in-Valve transcatheter aortic valve implantation (ViV TAVI) is emerging as an effective therapeutic option for bioprosthetic valve failure. Recently, concern has been raised for early valve deterioration of Mitroflow (Sorin) aortic bioprosthesis, with the development of prevalent stenosis. We report cases of pure severe aortic regurgitation (AR) due to early and mid-term prosthesis degeneration. From June 2018 to October 2019, three patients were treated in our division for the new appearance of severe intraprosthetic regurgitation. Patient 1 (man, 85-year-old) and patient 3 (woman, 83-year-old) had a Mitroflow n. 25 and n. 21 implanted, respectively, in 2012 and 2013 for severe aortic stenosis. Patient 2, a 67-year-old woman with Marfan syndrome underwent a Mitroflow n. 25 implant in 2008 for severe AR and presented chronic type-B aortic dissection. Patient 1 was diagnosed with severe AR in the ambulatory setting, while the other patients presented acute heart failure, requiring inotrope support and high doses intravenous diuretics, and in case 3, temporary extracorporeal ultrafiltration. All patients appeared at high surgical risk and were successfully treated with ViV TAVI, through the right axillary artery in patient 2, and through the femoral artery in patients 1 and 3. Results were good at short- and mid-term follow-up. In conclusion, early and midterm bioprosthesis degeneration with the development of severe AR is a possible complication of the Mitroflow aortic valve. ViV TAVI has been confirmed as a safe and effective therapeutic option in our cases.

Giant Right Coronary Artery Aneurysm Detected by Transthoracic Echocardiography.

Coronary artery aneurysms (CAAs) are rare findings caused by atherosclerosis in about 50% of cases. They are usually diagnosed using coronary angiography, cardiac computed tomography, or magnetic resonance imaging. In this report, we present a rare case of giant, isolated right CAA, detected by transthoracic echocardiography in an adult patient with unstable angina. Diameters of the aneurysm were 3.6 cm × 2.7 cm. Anterior-septal hypokinesia of the left ventricle was also noted. A comprehensive echocardiographic examination, including contrast study, excluded alternative diagnoses and supported the hypothesis of a coronary ectasia. The coronary angiography confirmed the diagnosis of giant coronary aneurysm and revealed a severe three-vessel disease. The patient was treated with cardiac surgery a few days later: two coronary artery bypass grafts and exclusion of the aneurysm by surgical legation were successfully performed.

Right heart dysfunction: from pathophysiologic insights to therapeutic options: a translational overview.

: The right ventricle has become increasingly studied in cardiovascular research. In this article, we describe specific pathophysiological characteristics of the right ventricle, with special focus on functional and molecular modifications as well as therapeutic strategies in right ventricular dysfunction, underlining the differences with the left ventricle. Then we analyze the main imaging modalities to assess right ventricular function in different clinical settings. Finally, we acknowledge main therapeutic advances for treatment of right heart diseases.

A new educational program in heart failure drug development: the Brescia international master program.

: Despite recent advances in chronic heart failure treatment, prognosis of acute heart failure patients remains poor with a heart failure rehospitalization rate or death reaching approximately 25% during the first 6 months after discharge. In addition, about half of these patients have preserved ejection fraction for which there are no evidence-based therapies. Disappointing results from heart failure clinical trials over the past 20 years emphasize the need for developing novel approaches and pathways for testing new heart failure drugs and devices. Indeed, many trials are being conducted without matching the mechanism and action of the drug with the clinical event. The implementation of these novel approaches should be coupled with the training of a new generation of heart failure physicians and scientists in the art and science of clinical trials. Currently, drug development is led by opinion leaders and experts who, despite their huge personal experience, were never trained systematically on drug development. The aim of this article is to propose a training program of 'drug development in Heart Failure'. A physician attending this course would have to be trained with a major emphasis on heart failure pathophysiology to better match mechanisms of death and rehospitalization with mechanism of action of the drug. Applicants will have to prove their qualifications and special interest in heart failure drug development before enrollment. This article should serve as a roadmap on how to apply emerging general principles in an innovative drug-development-in-heart-failure-process as well as the introduction of a new educational and mentorship program focusing on younger generations of researchers.

Pre-discharge and early post-discharge troponin elevation among patients hospitalized for heart failure with reduced ejection fraction: findings from the ASTRONAUT trial.

AIMS: Troponin levels are commonly elevated among patients hospitalized for heart failure (HF), but the prevalence and prognostic significance of early post-discharge troponin elevation are unclear. This study sought to describe the frequency and prognostic value of pre-discharge and post-discharge troponin elevation, including persistent troponin elevation from the inpatient to outpatient settings. METHODS AND RESULTS: The ASTRONAUT trial (NCT00894387; http://www.clinicaltrials.gov) enrolled hospitalized HF patients with ejection fraction ≤40% and measured troponin I prior to discharge (i.e. study baseline) and at 1-month follow-up in a core laboratory (elevation defined as >0.04 ng/mL). This analysis included 1469 (91.0%) patients with pre-discharge troponin data. Overall, 41.5% and 29.9% of patients had elevated pre-discharge [median: 0.09 ng/mL; interquartile range (IQR): 0.06-0.19 ng/mL] and 1-month (median: 0.09 ng/mL; IQR: 0.06-0.15 ng/mL) troponin levels, respectively. Among patients with pre-discharge troponin elevation, 60.4% had persistent elevation at 1 month. After adjustment, pre-discharge troponin elevation was not associated with 12-month clinical outcomes. In contrast, 1-month troponin elevation was independently predictive of increased all-cause mortality [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.18-2.13] and cardiovascular mortality or HF hospitalization (HR 1.28, 95% CI 1.03-1.58) at 12 months. Associations between 1-month troponin elevation and outcomes were similar among patients with newly elevated (i.e. normal pre-discharge) and persistently elevated levels (interaction P ≥ 0.16). The prognostic value of 1-month troponin elevation for 12-month mortality was driven by a pronounced association among patients with coronary artery disease (interaction P = 0.009). CONCLUSIONS: In this hospitalized HF population, troponin I elevation was common during index hospitalization and at 1-month follow-up. Elevated troponin I level at 1 month, but not pre-discharge, was independently predictive of increased clinical events at 12 months. Early post-discharge troponin I measurement may offer a practical means of risk stratification and should be investigated as a therapeutic target.

Mediterranean diet impact on cardiovascular diseases: a narrative review.

: Cardiovascular disease (CVD) accounts for more than 17 million deaths per year worldwide. It has been estimated that the influence of lifestyle on CVD mortality amounts to 13.7% for smoking, 13.2% for poor diet, and 12% for inactive lifestyle. These results deeply impact both the healthy status of individuals and their skills in working. The impact of CVD on productivity loss accounts for the 24% in total costs for CVD management.Mediterranean diet (MedD) can positively impact on natural history of CVD. It is characterized by a relatively high consumption of inexpensive and genuine food such as cereals, vegetables, legumes, nuts, fish, fresh fruits, and olive oil as the principal source of fat, low meat consumption and low-to-moderate consumption of milk, dairy products, and wine.Its effects on cardiovascular health are related to the significant improvements in arterial stiffness. Peripheral artery disease, coronary artery disease, and chronic heart failure are all positively influenced by the MedD. Furthermore, MedD lowers the risk of sudden cardiac death due to arrhythmias.The present narrative review aims to analyze the effects of MedD on CVD.

Preventing antiblastic drug-related cardiomyopathy: old and new therapeutic strategies.

Because of the recent advances in chemotherapeutic protocols, cancer survival has improved significantly, although cardiovascular disease has become a major cause of morbidity and mortality among cancer survivors: in addition to the well-known cardiotoxicity (CTX) from anthracyclines, biologic drugs that target molecules that are active in cancer biology also interfere with cardiovascular homeostasis.Pharmacological and non-pharmacological strategies to protect the cardiovascular structure and function are the best approaches to reducing the prevalence of cardiomyopathy linked to anticancer drugs. Extensive efforts have been devoted to identifying and testing strategies to achieve this end, but little consensus has been reached on a common and shared operability.Timing, dose and mode of chemotherapy administration play a crucial role in the development of acute or late myocardial dysfunction. Primary prevention initiatives cover a wide area that ranges from conventional heart failure drugs, such as ß-blockers and renin-angiotensin-aldosterone system antagonists to nutritional supplementation and physical training. Additional studies on the pathophysiology and cellular mechanisms of anticancer-drug-related CTX will enable the introduction of novel therapies.We present various typologies of prevention strategies, describing the approaches that have already been used and those that could be effective on the basis of a better understanding of pharmacokinetic and pharmacodynamic CTX mechanisms.

Preventing antiblastic drug-related cardiomyopathy: old and new therapeutic strategies.

Because of the recent advances in chemotherapeutic protocols, cancer survival has improved significantly, although cardiovascular disease has become a major cause of morbidity and mortality among cancer survivors: in addition to the well-known cardiotoxicity (CTX) from anthracyclines, biologic drugs that target molecules that are active in cancer biology also interfere with cardiovascular homeostasis.Pharmacological and non-pharmacological strategies to protect the cardiovascular structure and function are the best approaches to reducing the prevalence of cardiomyopathy linked to anticancer drugs. Extensive efforts have been devoted to identifying and testing strategies to achieve this end, but little consensus has been reached on a common and shared operability.Timing, dose and mode of chemotherapy administration play a crucial role in the development of acute or late myocardial dysfunction. Primary prevention initiatives cover a wide area that ranges from conventional heart failure drugs, such as ß-blockers and renin-angiotensin-aldosterone system antagonists to nutritional supplementation and physical training. Additional studies on the pathophysiology and cellular mechanisms of anticancer-drug-related CTX will enable the introduction of novel therapies.We present various typologies of prevention strategies, describing the approaches that have already been used and those that could be effective on the basis of a better understanding of pharmacokinetic and pharmacodynamic CTX mechanisms.

Risk of Cardiovascular Hospitalizations from Exposure to Coarse Particulate Matter (PM10) Below the European Union Safety Threshold.

The association between exposure to air pollution and acute cardiovascular (CV) events is well documented; however, limited data are available evaluating the public health safety of various "doses" of particular matter (PM) below currently accepted safety thresholds. We explored the cross-sectional association between PM with aerodynamic diameter <10 µm (PM10) and daily CV hospitalizations in Brescia, Italy, using Poisson regression models adjusted for age, gender, and meteorologic indices. Average daily exposure to PM10 obtained from arithmetic means of air pollution data were captured by 4 selected monitoring stations. PM10 data were expressed as daily means (lag 0-day) or 3-day moving averages (lag 3-day) and categorized according to the European Union daily limit value of 50 µg/m(3). From September 2004 to September 2007, data from 6,000 acute CV admissions to a tertiary referral center were collected. An increase of 1 µg/m(3) PM10 at lag 0-day was independently associated with higher rates of acute hospitalizations for composite CV-related events (relative risk [RR] 1.004, 95% confidence interval [CI] 1.002 to 1.006), acute heart failure (RR 1.004, 95% CI 1.001 to 1.008), acute coronary syndromes (RR 1.002, 95% CI 0.999 to 1.005), malignant ventricular arrhythmias (RR 1.004, 95% CI 0.999 to 1.010), and atrial fibrillation (RR 1.008, 95% CI 1.003 to 1.012). Similar results were obtained using PM10 lag 3-day data. The excess PM10 CV hospitalization risk (by lag 0-day and lag 3-day) did not vary significantly above and below the 50 µg/m(3) safety threshold or by age and gender. In conclusion, increased levels of PM10, even below the current limits set by the European Union, were associated with excess risk for admissions for acute CV events.

Spectrum of epidemiological and clinical findings in patients with heart failure with preserved ejection fraction stratified by study design: a systematic review.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) represents a major global and economic burden, but its epidemiological, clinical, and outcome data have varied according to study design. METHODS AND RESULTS: We conducted a systematic review of published HFpEF clinical trials and observational studies (community-based studies and registries) from August 1998 to July 2013 using PubMed and EMBASE databases. Two independent investigators manually screened and extracted relevant data. We included 62 articles (19 describing clinical trials, 12 describing community-based observational studies, and 31 describing registries). The ejection fraction (EF) cut-off values ranged widely for HFpEF from >40% to >55%. However, differences in EF cut-offs were not clearly associated with incidence and prevalence data across studies. Of all patients with heart failure in community studies, 33-84% had HFpEF, which tended to be higher than reported in registries. The HFpEF patients in included studies were primarily older, white (>70%) patients with hypertension (∼50-90%) and coronary artery disease (up to 60%). All-cause mortality and all-cause hospitalizations ranged from 13% to 23% (26-50 months follow-up) and 55% to 67% (37-50 months follow-up), respectively, in clinical trials; cardiovascular causes accounted for 70% of both outcomes. All-cause mortality tended to be higher in registries than in clinical trials and community-based observational studies up to 5 years into follow-up. CONCLUSIONS: Important differences in EF thresholds, epidemiological indices, clinical profiles, treatment patterns, and outcomes exist across contemporary HFpEF clinical trials, observational studies, and registries. Precision in definition and inclusion of more uniform populations may facilitate improved profiling of HFpEF patients.

[Chronic heart failure therapy: where we are and where we are going to]. / Terapia farmacologica dello scompenso cardiaco cronico: realtà e prospettive.

Despite significant advances in pharmacological and non-pharmacological therapy, epidemiological data from European and US hospitals show that the prevalence of heart failure (HF) hospitalization, especially for patients >65 years, continues to rise. Hospitalization for worsening HF is one of the most important predictors of short- and long-term outcomes in patients with chronic HF. There is therefore a clear need for new therapies that can work synergistically with standard medications to reverse the progression of the disease and improve myocardial efficiency. In the last years, researches in chronic HF focused on drugs that can exert a greater attenuation of neurohormonal activation and that can improve cardiac energy and substrate utilization.

Omega-3 Polyunsaturated Fatty Acid Supplementation: Mechanism and Current Evidence in Atrial Fibrillation.

Atrial fibrillation (AF) is the most prevalent arrhythmia and is associated with considerable morbidity and mortality. Available pharmacologic antiarrhythmic therapies are often ineffective in preventing the recurrence of AF, possibly because these drugs target a single pathophysiological mechanism. Given their beneficial effects on ventricular arrhythmias, omega-3 polyunsaturated fatty acids (n-3 PUFAs) have recently been investigated as possible candidates in the treatment of supraventricular arrhythmias. In this review, we explore the current understanding of the antiarrhythmic effects attributed to n-3 PUFAs including direct modulation of ionic channels, improvement of membrane fluidity, anti-inflammatory and antifibrotic effects, and modulation of sympatho-vagal balance. We will then focus on the results of epidemiologic studies exploring the associations between nutritional intake of n3 PUFAs and the incidence of AF, and will review the findings of the clinical trials investigating the effects of n-3 PUFAs supplementation in the prophylaxis of AF and in the prevention of its recurrences.

Effects of supplementation with polyunsaturated fatty acids in patients with heart failure.

Despite the clinical and prognostic improvement obtained with the current medical treatment, heart failure (HF) continues to have high morbidity and mortality and its prevalence is increasing in most regions of the world. Thus, there is a need for novel adjunctive therapies that act independently of current neurohormonally and haemodynamically oriented drugs. Nutritional approaches are particularly attractive because they could work additively with established therapies without negative hemodynamic effects. There is growing evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation positively impacts established pathophysiological mechanisms in HF and thus has a potential role for preventing and treating HF. The results of the GISSI-HF trial have indicated that, in patients with chronic HF on evidence-based therapy, long term treatment with PUFAs reduced mortality and hospitalizations for cardiovascular reasons, irrespective of etiology and left ventricular (LV) ejection fraction (EF). The purpose of this review is to summarize the evidence emerged from studies conducted so far on the effect of n-3 PUFAs in HF.