Trends of Pulmonary Embolism-Related Sudden Cardiac Death in the United States, 1999-2019.

OBJECTIVES: Up-to-date population-based data on pulmonary embolism (PE)-related sudden cardiac death (SCD) mortality trends in the United States (US) are scant. We assess the current trends in PE-related SCD mortality in US over the past two decades and determine differences by sex, race, ethnicity, age, and census region. METHODS: We extracted PE-related SCD mortality rates from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1999 to 2019, in patients aged ≥ 15 years old. Age-adjusted mortality rates (AAMRs) were assessed using the Joinpoint regression modeling and expressed as estimated average annual percentage change (AAPC) with relative 95% confidence intervals (CIs). RESULTS: Between 1999 and 2019, the AAMR from acute PE-related SCD mortality in the US linearly increased [AAPC: +2.4% (95% CI: 2.2 to 2.6), p < 0.001)]. The AAMR increase was more pronounced in men [AAPC: +2.8% (95% CI: 2.6 to 2.9), p < 0.001], Whites [AAPC: +2.7% (95% CI: 2.3 to 3.1), p < 0.001], Latinx/Hispanic patients [AAPC:+2.0% (95% CI: 1.2 to 2.8), p < 0.001], subjects younger than 65 years [AAPC: +2.4% (95% CI: 2.1 to 2.6), p < 0.001] and in residents of rural areas [AAPC: +3.6% (95% CI: 3.3 to 3.9), p < 0.001]. Moreover, higher percentages of PE-related SCD and the relative absolute number of deaths were observed in the South compared with other geographical regions. CONCLUSIONS: PE-related SCD mortality in the US has increased over the last two decades. Stratification by race, ethnicity, urbanization, and census region demonstrates ethnoracial and regional disparities that require further investigation and remedy.

ANMCO/SIMEU consensus document on the use of reversal agents for antithrombotic therapies in patients with ongoing bleeding or at high risk of haemorrhagic events.

In recent decades, an incredible evolution in antithrombotic therapies used for treating patients with atherosclerosis, atrial fibrillation, and venous thromboembolism has been observed, leading to the availability of increasingly safe drugs. Nonetheless, bleeding complications remain a significant concern, with considerable health, social, and economic implications. To improve the acute management of patients experiencing or at risk for major bleeding events, specific reversal agents for antithrombotic drugs have been recently developed. While these agents demonstrate effectiveness in small-scale pharmacodynamic studies and clinical trials, it is imperative to balance the benefits of reversing antiplatelet or anticoagulant therapy against the risk of prothrombotic effects. These risks include the potential loss of antithrombotic protection and the prothrombotic tendencies associated with bleeding, major surgery, or trauma. This joint document of the Italian Association of Hospital Cardiologists (Associazione Nazionale Medici Cardiologi Ospedalieri) and the Italian Society of Emergency Medicine (Società Italiana di Medicina d'Emergenza-Urgenza) delineates the key features and efficacy of available reversal agents. It also provides practical flowcharts to guide their use in patients with active bleeding or those at elevated risk of major bleeding events.

Italian Association of Hospital Cardiologists position paper-obesity in adults: a clinical primer.

Obesity is a chronic and relapsing disease characterized by the interaction between individual predispositions and an obesogenic environment. Recent advances in understanding the mechanisms of energetic homoeostasis paved the way to more effective therapeutic approaches compared with traditional treatments. Since obesity is a complex disease, it necessitates a multi-disciplinary approach whose implementation remains challenging. Nonetheless, emerging pharmacological interventions appear promising. Currently, therapeutic success is discreet in the short term but often fails to maintain long-term weight loss due to a high likelihood of weight regain. Cardiologists play a key role in managing patients with obesity, yet often lack familiarity with its comprehensive management. The aim of this document is to summarize knowledge to consolidate essential knowledge for clinicians to effectively treat patients living with obesity. The paper emphasizes the pivotal role of a strong patient-clinician relationship in navigating successful treatment. We analyse the criteria commonly used to diagnose obesity and point out the strengths and limitations of different criteria. Furthermore, we discuss the role of obesiologists and the contributions of cardiologists. In addition, we detail key components of effective therapeutic strategies, including educational aspects and pharmacological options.

Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) scientific statement on the simplification of the drug regimen for secondary cardiovascular prevention.

The issue of suboptimal drug regimen adherence in secondary cardiovascular prevention presents a significant barrier to improving patient outcomes. To address this, the utilization of drug combinations, specifically single pill combinations (SPCs) and polypills, was proposed as a strategy to simplify treatment regimens. This approach aims to enhance treatment accessibility, affordability, and adherence, thereby reducing healthcare costs and improving patient health. The document is an Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) scientific statement on simplifying drug regimens for secondary cardiovascular prevention. It discusses the underuse of treatments despite available, effective, and accessible options, highlighting a significant gap in secondary prevention across different socio-economic statuses and countries. The statement explores barriers to implementing evidence-based treatments, including patient, healthcare provider, and system-related challenges. The paper also reviews international guidelines, the role of SPCs and polypills in clinical practice, and their economic impact, advocating for their use in secondary prevention to improve patient outcomes and adherence.

Risk of incident heart failure after COVID-19 recovery: a systematic review and meta-analysis.

Patients recovered from COVID-19 have an increased incidence of cardiovascular disease and heart structural changes. The aim of the present manuscript is to assess the risk of incident heart failure (HF) after COVID-19 infection. Data were obtained searching MEDLINE and Scopus for all studies published at any time up to September 1, 2022 reporting the risk of incident HF in COVID-19 recovered patients. The cumulative post-COVID-19 incidence and risk of incident HF were pooled using a random effects model and presented with the corresponding 95% confidence interval (CI). Statistical heterogeneity was measured using the Higgins I2 statistic. Overall, 21,463,173 patients (mean age 54.5 years, 58.7% males) were analyzed. Among them, 1,628,424 had confirmed COVID-19 infection while the remaining 19,834,749 represented the controls. The mean length of follow-up was 9.2 months. A random effect model revealed a pooled incidence of post COVID-19 HF in 1.1% of cases (95% CI: 0.7-1.6, I2: 99.8%). Moreover, recovered COVID-19 patients showed an increased risk of incident HF (HR: 1.90, 95% CI: 1.54-3.24, p < 0.0001, I2 = 96.5%) in the same follow-up period. Meta-regression showed a direct relationship for the risk of incident HF using age (p = 0.001) and hypertension (HT) (p = 0.02) as moderators, while an inverse association was observed when the follow-up length was adopted as moderating variable (p = 0.01). COVID-19 survivors had an additional 90% risk of developing HF after COVID-19 infection in the long-term period. This risk was directly related with age and previous history of HT especially in the early post-acute phase of the infection.

Trends in ventricular fibrillation/flutter mortality in US population, 1999 to 2019.

BACKGROUND: The Ventricular fibrillation and flutter (VF/VFL)-related mortality trends in the United States (US) population have not yet been investigated. We aimed to assess the trends of VT/VFL-related mortality from 1999 to 2019 among subjects aged more than 15 years old in the US. METHODS: Data derived from the Centers for Disease Control and Prevention's (CDC) WONDER were analyzed between 1999 and 2019 for VF/VFL-related mortality in subjects aged more than 15 years of age. Adjusted mortality rates (AAMRs) per 100,000 people by year, sex, race and urban-rural status with relative confidence intervals (CIs) were determined. Both the average annual percent change (AAPC) and the annual percent change (APC) with 95% Cis were calculated. RESULTS: Between 1999 and 2019, 242,125 VT/VFL-related deaths occurred in the US. The overall AAMR steadily declined [AAPC -4.4% (95% CI: -4.7 to -4.0, p < .0001)]. Women showed a more pronounced AAMRs decline [AAPC: -4.8% (95% CI: -5.3 to -4.3, p < .0001). AAMR steadily declined in white subjects and in those of other races [AAPC: -4.5 (95% CI: -4.7 to -4.2, p < .0001) and AAPC: -4.3 (95% CI: -5.1 to -3.5, p < .001), respectively]. Conversely, African Americans showed a steadily AMMR decline between 1999 and 2007 [APC: -8.3 (95% CI: -9.2 to -7.3, p < .0001)], followed by a period of stability from 2007 to 2019 (p = .73). A similar decline was observed for the AAMR among subjects living in urban and rural areas. CONCLUSIONS: VT/VFL-related mortality steadily decreased between 1999 and 2019 in US. Despite the encouraging results, further efforts are needed to prevent VF/VFL-related mortality in US subjects.

Impact of clinical profile at admission on the outcomes in patients hospitalized for acute pulmonary embolism: data from the IPER Registry.

Acute pulmonary embolism (PE) is characterized by a large heterogeneity of clinical presentation and disease course. We investigate whether different symptom PE phenotypes in hemodynamically stable PE could be associated with 30-day mortality risk. Hemodynamically stable patients from the multicentre, prospective Italian Pulmonary Embolism Registry (IPER) (September 2006-August 2010) presenting the most common four clinical phenotypes (< 24 h onset dyspnoea, chest pain, pleuritic pain and phlebitis) at admission were included and compared to those who were asymptomatic at admission. Overall, 1365 (mean age 68.7 ± 15.3 years, 609 males) were evaluated. Recent onset dyspnoea (< 24 h), chest pain, pleuritic pain and phlebitis were observed in 28.4%, 19.7%, 12.9% and 25.2%, respectively while asymptomatic patients represented the remaining 13.6% of cases. PE presenting with recent dyspnoea onset and chest pain had a lower 30-day overall survival (log-rank p = 0.01 and p < 0.001, respectively). By contrast, there were no significant differences when comparing patients with pleuritic pain or phlebitis (log-rank p = 0.2). Similar findings were confirmed at the Cox multivariate regression analysis which indicated a higher mortality risk in patients with chest pain [HR 3.21, 95% CI 2.16-4.78, p < 0.001] or recent dyspnoea [HR 2.12, 95% CI 1.22-3.87, p = 0.002] independent of age, heart rate, presence of right ventricular dysfunction, positive cardiac troponin and administration of systemic thrombolysis. Hemodynamically stable PE patients presenting with chest pain or recent onset dyspnoea had a lower 30-day survival compared to those asymptomatic or presenting pleuritic or phlebitis pain.Trial registry ClinicalTrials.gov; No: NCT01604538).

Prevalence of pre-existing peripheral artery disease in COVID-19 patients and relative mortality risk: Systematic review and meta-analysis.

INTRODUCTION: This study aims to assess prevalence and prognostic implications of pre-existing peripheral artery disease (PAD) in patients infected by the SARS-CoV-2 by means of a systematic review and meta-analysis. MATERIAL AND METHODS: We searched MEDLINE and Scopus to locate all the articles published up to 10 December 2021, reporting data on pre-existing PAD among COVID-19 survivors (S) and non survivors (NS). The pooled prevalence of pre-existing PAD in COVID-19 patients was calculated using a random effects model and presenting the related 95% confidence interval (CI), while the mortality risk was estimated using the Mantel-Haenszel random effects models with odds ratio (OR) and related 95% CI. Statistical heterogeneity was measured using the Higgins I2 statistic. RESULTS: Eight investigations, enrolling 13,776 COVID-19 patients (mean age: 67.1 years, 3.863 males), met the inclusion criteria and were included in the final analysis. The pooled prevalence of pre-existing PAD was 5.7% of cases (95% CI: 3.8-8.4%, p < 0.0001), with high heterogeneity (I2 = 84.5%), which was directly correlated with age (p < 0.0001), previous hypertension (p = 0.003), and dyslipidaemia (p = 0.02) as demonstrated by the meta-regression. Moreover, pre-existing PAD was significantly associated with higher risk of short-term death in patients with SARS-CoV-2 infection (OR: 2.78, 95% CI: 2.37-3.27, p < 0.0001 I2 = 0%); the sensitivity analysis confirmed yielded results. CONCLUSIONS: Pre-existing PAD represents a comorbidity in about 1 out of 6 COVID-19 patients, but it is associated with a twofold higher risk of short-term mortality.

Coronary artery cavitation as a trigger for atherosclerotic plaque progression: a simplified numerical and computational fluid dynamic demonstration.

BACKGROUNDS: Coronary cavitation is supposed to be generated by both concentric and eccentric coronary artery stenosis which propagates downstream the vessel, creating microbubbles which exploded when the fluid pressure was lower than the vapor pressure at a local thermodynamic state. OBJECTIVE: To assess, using numerical and computational fluid dynamic analysis (CFD), the potential of cavitation to both induce damage to coronary artery endothelium and to promote atherosclerotic plaque progression. METHODS: We retrospectively reviewed the data 12 consecutive patients evaluated between 1st January 2013 and 1st January 2014 with an isolated hemodynamically significant Left Main (LM) disease. The patient specific geometries have been reconstructed. Bubble velocity has been calculated in accordance with Newton's second law. Both the forces arising from the bubbles' interaction with the continuous phase and impact with the endothelium have been evaluated. The impact of turbulence on the motion of bubbles have been modelled with a dispersion model. RESULTS: Among the 12 patients retrospectively analysed [8 males, mean age 68.2 ± 12.8 years old], the mean LM stenosis was 72.3 ± 3.6%. As expected, in all subjects, LM stenoses induced cavitation which propagates downstream the vessel creating microbubbles. The higher concentration of vapor region was detected before the carina (within 0.8 to 1.3 cm from the stenosis). Due to the pressure gradient generated by the stenosis, formation of a re-entry jet which penetrates each bubble generated a shock wave. Before the carina, the mean bubbles radius observed was 4.2 ± 1.4 µm, which generated a mean peak pressure of 3.9 ± 0.5 MPa when they explode. CONCLUSION: The cavitation phenomenon is effectively generated in a model of LM bifurcation and instantaneous pressure-peaks due to collapses of vapor bubbles resulted in a measurable dynamic load on vessel wall potentially able to induce endothelial damage.

Clinical evaluation of bempedoic acid for the treatment of hyperlipidaemia.

Bempedoic acid (BA) is a novel first-in-class oral lipid-lowering therapy. BA has been approved by the European Medicinal Agency and Food and Drug Administration and has been commercialised throughout Europe since the end of 2020 as an add-on therapy in patients at high/very-high cardiovascular risk that are not at LDL-C goals with current lipid-lowering treatments. Recently, Italian lipid management experts gathered to discuss several open questions on BA characteristics and BArelated practical clinical issues. The panel permitted collection of its opinions in a ten Q&A format. AIM: The aim of this viewpoint is to discuss and answer several open questions on BA characteristics and BA-related practical clinical issues. DATA SYNTHESIS: The data includes main phase III studies, subanalysis and meta-analysis on BA. CONCLUSIONS: The panel permitted collection of its opinions in a ten Q&A format.

Electrocardiographic predictors of echocardiographic response in cardiac resynchronization therapy: Update of an old story.

BACKGROUND: A better selection of patients with left bundle branch block (LBBB) might increase the response to cardiac resynchronization therapy (CRT). The aim of the study was to investigate the association between the Strauss criteria, absence of S wave in V5-V6, the Selvester score and response to CRT. METHODS AND RESULTS: The retrospective analysis included all consecutive patients having undergone implantation of biventricular defibrillators in primary prevention between 2018 and 2020. The final analysis included 236 patients (mean age 69.7 ± 9.9; 77.5% of males). The Strauss criteria were significantly associated with CRT response (p < 0.01) with a sensitivity of 71.3% and specificity of 64.1%. The Strauss criteria along with the absence of S wave in V5 and V6 showed a sensitivity of 56.7%, a specificity of 82.6% and a positive predictive value of 90.5%. The Selvester score was significantly and inversely associated with CRT response (OR 0.818, 95% CI 0.75-0.89; p < 0.001). The multivariable model showed that left ventricular ejection fraction (LVEF) and QRS duration (≥140 ms in males and ≥ 130 ms in females) were independently associated with CRT response (respectively OR 0.92, CI 95% 0.86-0.98, p = 0.01 and OR 3.70, CI 95% 1.12-12.21, p = 0.03). CONCLUSIONS: Strauss criteria, especially in association with absence of S wave in V5 and V6, were able to increase specificity and positive predictive value for predicting CRT response. The Selvester score was inversely associated with CRT response. Finally, LVEF and QRS duration were independently associated with echocardiographic response to CRT.

Intraventricular Thrombus Formation and Embolism in Takotsubo Syndrome: Insights From the International Takotsubo Registry.

OBJECTIVE: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×103 cells/µL emerged as independent predictors for thrombus formation or embolism. CONCLUSIONS: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

Team working in the modern medicine: The paradigm of electrophysiology.

In modern Medicine, team working has become crucial to guarantee favorable outcomes in most therapeutical procedures. Electrophysiology (EP) represents an exemplary paradigm of it. Herein, the role of the EP staff members and the importance of cooperation before, during and after the procedure is highlighted. Moreover, the strategies and the future challenges for developing a strong and efficient teamwork through a continuous process of improvement (the so-called "Kaizen Methodology") are widely discussed.

Coexistence and outcome of coronary artery disease in Takotsubo syndrome.

AIMS: Takotsubo syndrome (TTS) is an acute heart failure syndrome, which shares many features with acute coronary syndrome (ACS). Although TTS was initially described with angiographically normal coronary arteries, smaller studies recently indicated a potential coexistence of coronary artery disease (CAD) in TTS patients. This study aimed to determine the coexistence, features, and prognostic role of CAD in a large cohort of patients with TTS. METHODS AND RESULTS: Coronary anatomy and CAD were studied in patients diagnosed with TTS. Inclusion criteria were compliance with the International Takotsubo Diagnostic Criteria for TTS, and availability of original coronary angiographies with ventriculography performed during the acute phase. Exclusion criteria were missing views, poor quality of angiography loops, and angiography without ventriculography. A total of 1016 TTS patients were studied. Of those, 23.0% had obstructive CAD, 41.2% had non-obstructive CAD, and 35.7% had angiographically normal coronary arteries. A total of 47 patients (4.6%) underwent percutaneous coronary intervention, and 3 patients had acute and 8 had chronic coronary artery occlusion concomitant with TTS, respectively. The presence of CAD was associated with increased incidence of shock, ventilation, and death from any cause. After adjusting for confounders, the presence of obstructive CAD was associated with mortality at 30 days. Takotsubo syndrome patients with obstructive CAD were at comparable risk for shock and death and nearly at twice the risk for ventilation compared to an age- and sex-matched ACS cohort. CONCLUSIONS: Coronary artery disease frequently coexists in TTS patients, presents with the whole spectrum of coronary pathology including acute coronary occlusion, and is associated with adverse outcome. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01947621.

ANMCO POSITION PAPER: The cardiological clinical activities in the transition phase of the COVID-19 pandemic.

Infections by SARS CoV2 - COVID-19 became in a short time a worldwide health emergency. The present SARS-CoV-2 pandemic induced in a short time, an unprecedented impact on public health and on the pre-existing care pathways. In order to appropriately address this epidemiological emergency, urgent solutions were needed, such as remodelling or stopping hospitalization and deferrable clinical activities to avoid spreading the SARS-CoV-2 infection. After the first emergency lockdown phase, care pathways must guarantee healthcare to patients and preserve the safety of the healthcare personnel and of all the other subjects that refer to the cardiological surgeries. Rigorous prescriptive appropriateness of the requested exams with consequent reduction of unnecessary examinations is an essential requirement to preserve prioritized diagnostic and care pathways to patients in need, minimizing the risks connected to the SARS-CoV-2 contagion in hospitals. Telemedicine services represent a valid answer to cardiovascular disease patients' need for care and assistance, including those in quarantine and voluntary isolation. These services successfully contribute to fight the spread of the virus guaranteeing at the same time therapy and support through remote services that must therefore be considered a resource to be implemented and enhanced. This document has to be used by the healthcare personnel working in hospitals and in district offices, if applicable, and aims at managing patients, in complete safety and considered not suspect/not probable ('not at risk') of SARS-CoV-2 infection, eligible for diagnostic activity and subsequent therapy in outpatient surgeries. In particular, this document provides indications for patient evaluation to prevent COVID-19 exposure, gives general indications on managing appointments and waiting rooms, on how to strictly adhere to environmental safety measures, on the proper use of Individual Protective Equipment (IPE). It also provides specific indications for outpatient service procedures, like electrocardiogram, cardiologic examination, cardiologic checkup, Dynamic Holter Electrocardiogram, Transthoracic Echocardiography, Echo Stress, Transoesophageal Echocardiography, Bike Ergometer stress test, Ergospirometry, Outpatient Checkup of implantable electronic cardiac devices.

An unusual case of AV block.

Nerium oleander is an evergreen small tree, very used in some countries such as India and in Sri Lanka as a self-medication method. We report a case of a 55 year-old man with intermittent, advanced AV block secondary to oleander intoxication.

Herpes zoster infection and statins: which implications in clinical practice?

Herpes zoster (HZ), which is caused by reactivation of latent varicella zoster virus (VZV), constitutes a major public health concern in both short- and long-term periods. Over the last years, several epidemiological studies have demonstrated that statin use is associated with increased risk of HZ at cerebral level. Because statins are among the most popular and best-selling drugs in western countries, this potential negative pleiotropic effect could have important implications in the daily clinical practice. In the present manuscript, we reviewed the available data on the statin use and the relative risk of HZ infection.