Not Just CTEPH: A Narrative Review on the Spectrum Approach to Postpulmonary Embolism Conditions.

Three mutually exclusive entities can underlie a postpulmonary embolism syndrome (PPES): not obstructed postpulmonary embolism syndrome (post-PE dyspnea), chronic thromboembolic pulmonary disease (CTEPD), and chronic thromboembolic pulmonary hypertension (CTEPH). Cardiorespiratory impairment in CTEPH and CTEPD underlies respiratory and hemodynamic mechanisms, either at rest or at exercise. Gas exchange is affected by the space effect, the increased blood velocity, and, possibly, intracardiac right to left shunts. As for hemodynamic effects, after a period of compensation, the right ventricle dilates and fails, which results in retrograde and anterograde right heart failure. Little is known on the pathophysiology of post-PE dyspnea, which has been reported in highly comorbid with lung and heart diseases, so that a "two-hit" hypothesis can be put forward: it might be caused by the acute myocardial damage caused by pulmonary embolism in the context of preexisting cardiac and/or respiratory diseases. More than one-third of PE survivors develops PPES, with only a small fraction (3-4%) represented by CTEPH. A value of ≈3% is a plausible estimate for the incidence of CTEPD. Growing evidence supports the role of CTEPD as a hemodynamic phenotype intermediate between post-PE dyspnea and CTEPH, but it still remains to be ascertained whether it constantly underlies exercise-induced pulmonary hypertension and if it is a precursor of CTEPH. Further research is needed to improve the understanding and the management of CTEPD and post-PE dyspnea.

Pulmonary hypertension associated to left heart disease: Phenotypes and treatment.

Pulmonary hypertension associated to left heart disease (PH-LHD) refers to a clinical and haemodynamic condition of pulmonary hypertension associated with a heterogeneous group of diseases affecting any of the compartments that form the left ventricle and left atrium. PH-LHD is the most common cause of PH, accounting for 65-80 % of diagnoses. Based on the haemodynamic phase of the disease, PH-LDH is classified into three subgroups: postcapillary PH, isolated postcapillary PH and combined pre-postcapillary PH (CpcPH). Several signaling pathways involved in the regulation of vascular tone are dysfunctional in PH-LHD, including nitric oxide, MAP kinase and endothelin-1 pathways. These pathways are the same as those altered in PH group 1, however PH-LHD can heardly be treated by specific drugs that act on the pulmonary circulation. In this manuscript we provide a state of the art of the available clinical trials investigating the safety and efficacy of PAH-specific drugs, as well as drugs active in patients with heart failure and PH-LHD. We also discuss the different phenotypes of PH-LHD, as well as molecular targets and signaling pathways potentially involved in the pathophysiology of the disease. Finally we will mention some new emerging therapies that can be used to treat this form of PH.

Cardiovascular outcomes and molecular targets for the cardiac effects of Sodium-Glucose Cotransporter 2 Inhibitors: A systematic review.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new class of glucose-lowering drugs traditionally used to control blood glucose levels in patients with type 2 diabetes mellitus, have been proven to reduce major adverse cardiovascular events, including cardiovascular death, in patients with heart failure irrespective of ejection fraction and independently of the hypoglycemic effect. Because of their favorable effects on the kidney and cardiovascular outcomes, their use has been expanded in all patients with any combination of diabetes mellitus type 2, chronic kidney disease and heart failure. Although mechanisms explaining the effects of these drugs on the cardiovascular system are not well understood, their effectiveness in all these conditions suggests that they act at the intersection of the metabolic, renal and cardiac axes, thus disrupting maladaptive vicious cycles while contrasting direct organ damage. In this systematic review we provide a state of the art of the randomized controlled trials investigating the effect of SGLT2i on cardiovascular outcomes in patients with chronic kidney disease and/or heart failure irrespective of ejection fraction and diabetes. We also discuss the molecular targets and signaling pathways potentially explaining the cardiac effects of these pharmacological agents, from a clinical and experimental perspective.

Current Antithrombotic Treatments for Cardiovascular Diseases: A Comprehensive Review.

Antithrombotic therapies (ATT) play a pivotal role in the management of cardiovascular diseases, aiming to prevent ischemic events while maintaining a delicate balance with the patient's bleeding risk. Typically, ATT can be classified into antiplatelet and anticoagulant therapies. Their application spans a broad spectrum of cardiovascular conditions, ranging from ischemic heart disease to atrial fibrillation, encompassing venous thromboembolisms and innovative structural interventional cardiology procedures. The global burden of cardiovascular diseases is steadily increasing, often giving rise to overlapping clinical presentations. Accordingly, the adoption of combined pharmacological approaches becomes imperative, potentially disrupting the delicate equilibrium between ischemic and bleeding risk, thus leading to nuanced pharmacotherapeutic pathways. In this context, contemporary investigations strive to identify a convergence point that optimizes the duration of medical therapy while addressing the need for antithrombotic effects, especially in the context of ischemic heart disease. This review aims to comprehensively revisit the main antithrombotic strategies in cardiovascular diseases, with the intention of enhancing a systematic approach which is key for the effective clinical management of these patients. Also, the review will examine the most impactful studies that have established the groundwork for current scientific evidence, with acknowledgement of special populations. Finally, we will cast a gaze into the future of this dynamic and evolving research field, exploring forthcoming perspectives and advancements.

Efficacy, safety, adherence and persistence of PCSK9 inhibitors in clinical practice: A single country, multicenter, observational study (AT-TARGET-IT).

BACKGROUND AND AIMS: Proprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9i) are recommended in patients at high and very-high cardiovascular (CV) risk, with documented atherosclerotic CV disease (ASCVD), and for very-high risk patients with familial hypercholesterolaemia not achieving LDL-cholesterol (LDL-C) goal while receiving maximally tolerated dose of lipid-lowering therapy (LLT). However, single country real-life data, reporting the use of PCSK9i in clinical practice, are limited. Therefore, we designed AT-TARGET-IT, an Italian, multicenter, observational registry on the use of PCSK9i in clinical practice. METHODS: All data were recorded at the time of the first prescription and at the latest observation preceding inclusion in the study. RESULTS: 798 patients were enrolled. The median reduction in LDL-C levels was 64.9%. After stratification for CV risk, 63.8% achieved LDL-C target; of them, 83.3% took LLTs at PCSK9i initiation and 16.7% did not. 760 patients (95.2%) showed high adherence to therapy, 13 (1.6%) partial adherence, and 25 (3.1%) poor adherence. At 6 months, 99.7% of patients enrolled in the study remained on therapy; there were 519 and 423 patients in the study with a follow-up of at least 12 and 18 months, respectively. Persistence in these groups was 98.1% and 97.5%, respectively. Overall, 3.5% of patients discontinued therapy. No differences in efficacy, adherence, and persistence were found between alirocumab and evolocumab. CONCLUSIONS: PCSK9i are safe and effective in clinical practice, leading to very high adherence and persistence to therapy, and achievement of recommended LDL-C target in most patients, especially when used as combination therapy.

Secondary prevention and follow-up of patients with ACS and not-at-target LDL: An Italian real-world retro-prospective analysis by the inertia group.

Background: In patients with recent ACS, the latest ESC/EAS guidelines for management of dyslipidaemia recommend intensification of LDL-C-lowering therapy. Objective: Report a real-world picture of lipid-lowering therapy prescribed and cholesterol targets achieved in post-ACS patients before and after a specific educational program. Methods: Retrospective data collection prior to the educational course and prospective data collection after the course of consecutive very high-risk patients with ACS admitted in 2020 in 13 Italian cardiology departments, and with a non-target LDL-C level at discharge. Results: Data from 336 patients were included, 229 in the retrospective phase and 107 in the post-course prospective phase. At discharge, statins were prescribed in 98.1% of patients, alone in 62.3% of patients (65% of which at high doses) and in combination with ezetimibe in 35.8% of cases (52% at high doses). A significant reduction was obtained in total and LDL cholesterol (LDL-C) from discharge to the first control visit. Thirty-five percent of patients achieved a target LDL-C <55 mg/dL according to ESC 2019 guidelines. Fifty percent of patients achieved the <55 mg/dL target for LDL-C after a mean of 120 days from the ACS event. Conclusions: Our analysis, though numerically and methodologically limited, suggests that management of cholesterolaemia and achievement of LDL-C targets are largely suboptimal and need significant improvement to comply with the lipid-lowering guidelines for very high CV risk patients. Earlier high intensity statin combination therapy should be encouraged in patients with high residual risk.

[Role of fractional flow reserve for invasive functional evaluation in surgical myocardial revascularization: available evidence and state of the art]. / Ruolo della valutazione funzionale mediante riserva frazionale di flusso nella rivascolarizzazione miocardica chirurgica: evidenze disponibili e stato dell'arte.

Fractional flow reserve (FFR) is the ratio of distal to proximal pressure during maximal hyperemia and indirectly estimates the blood flow across a stenotic coronary artery and the related degree of myocardial ischemia. Several studies have investigated the role of FFR in the setting of percutaneous myocardial revascularization and further research is ongoing. However, current evidence on FFR-guided surgical myocardial revascularization is controversial and limited. The main scientific interest is to clarify whether FFR-guided coronary artery bypass surgery is associated with clinical benefits in terms of mortality, myocardial infarction, major adverse cardiovascular events, minimally invasive surgical access compared with sternotomy and off-pump surgery. Furthermore some data suggest that conduit selection for coronary artery bypass grafting and surgical technique might be affected by FFR value. The aim of this article is to review the most recent available evidence about FFR-guided coronary artery bypass grafting and to discuss clinical implications and future perspectives.

Clinical Discussions in Antithrombotic Therapy Management in Patients With Atrial Fibrillation: A Delphi Consensus Panel.

BACKGROUND: In recent years, direct-acting oral anticoagulants (DOACs) have entered clinical practice for stroke prevention in non-valvular atrial fibrillation or prevention and treatment of venous thromboembolism. However, remaining uncertainty regarding DOAC use in some clinical scenarios commonly encountered in the real world has not been fully explored in clinical trials. METHODS: We report on use of a Delphi consensus process on DOAC use in non-valvular atrial fibrillation patients. The consensus process dealt with 9 main topics: (i) DOACs vs vitamin K antagonists in atrial fibrillation (AF) patients; (ii) therapeutic options for patients with stable total time in range treated with vitamin K antagonists; (iii) therapeutic options for patients aged > 85 years; (iv) therapeutic management of hyperfiltering patients; (v) pharmacologic interactions; (vi) therapeutic options in the long-term treatment (prevention) of patients with AF and acute coronary syndrome after the triple therapy; (vii) low doses of DOACs in AF patients; (viii) ischemic stroke in patients inappropriately treated with low doses of DOACs; (ix) management of patients taking DOACs with left atrial appendage thrombosis. RESULTS: A total of 101 physicians (cardiologists, internists, geriatricians, and hematologists) from Italy expressed their level of agreement on each statement by using a 5-point Likert scale (1 = strongly disagree; 2 = disagree; 3 = somewhat agree; 4 = agree; 5 = strongly agree). Votes 1-2 were considered to be disagreement; votes 3-5 were considered to be agreement. Agreement among the respondents of ≥ 66% for each statement was considered consensus. A brief discussion of the results for each topic is also reported. CONCLUSIONS: In clinical practice, there is still uncertainty on DOAC use, especially in elderly, fragile, comorbid, and hyperfiltering patients.

CONTEXTE: Depuis quelques années, les cliniciens prescrivent des anticoagulants oraux directs (AOD) pour prévenir les accidents vasculaires cérébraux (AVC) chez les patients présentant une fibrillation auriculaire (FA) non valvulaire ou pour prévenir et traiter les thromboembolies veineuses. Cependant, les doutes que suscite encore l'emploi des AOD dans certains contextes courants de la pratique clinique n'ont pas encore été bien explorés dans le cadre des études cliniques. MÉTHODOLOGIE: Nous avons utilisé la méthode de Delphes, une démarche visant à dégager un consensus, afin d'évaluer le recours aux AOD chez des patients présentant une FA non valvulaire. L'étude comprenait 9 thèmes principaux : i) utilisation des AOD et des antagonistes de la vitamine K chez les patients présentant une FA; ii) options thérapeutiques pour les patients traités par un antagoniste de la vitamine K dont l'état se maintient depuis un certain temps dans une plage de valeurs normales; iii) options thérapeutiques pour les patients âgés de plus de 85 ans; iv) prise en charge thérapeutique des patients souffrant d'hyperfiltration; v) interactions pharmacologiques; vi) options thérapeutiques pour le traitement prolongé (préventif) des patients présentant une FA et un syndrome coronarien aigu après une trithérapie; vii) utilisation des AOD à faible dose chez les patients présentant une FA; viii) AVC ischémique chez les patients traités de façon inappropriée par un AOD à faible dose; ix) prise en charge des patients prenant un AOD qui présentent une thrombose de l'appendice auriculaire gauche. RÉSULTATS: Au total, 101 médecins (cardiologues, internistes, gériatres et hématologues) italiens ont exprimé leur degré d'accord avec chacun des énoncés proposés sur une échelle de Likert à 5 points (1 = tout à fait en désaccord; 2 = en désaccord; 3 = moyennement d'accord; 4 = d'accord; 5 = tout à fait d'accord). Une note de 1 ou 2 a été considérée comme un désaccord et une note de 3, 4 ou 5, comme un accord. On considérait qu'il y avait un consensus si 66 % ou plus des répondants étaient d'accord avec l'énoncé. Nous présentons également brièvement les résultats obtenus pour chacun des thèmes. CONCLUSIONS: Dans la pratique clinique, l'emploi des AOD soulève encore des doutes, en particulier chez les patients âgés, fragiles ou présentant des affections concomitantes ou une hyperfiltration.

The Role of Multimodality Cardiovascular Imaging in Peripartum Cardiomyopathy.

The burden of pregnancy-related heart disease has dramatically increased over the last decades due to the increasing age at first pregnancy and higher prevalence of cardiovascular risk factors such as diabetes, hypertension, and obesity. Pregnancy is associated with physiological changes in the cardiovascular system, including hemodynamic, metabolic, and hormonal adaptations to meet the increased metabolic demands of the mother and fetus. It has been postulated that pregnancy may act as a cardiovascular stress test to identify women at high risk for heart disease, where the inability to adequately adapt to the physiologic stress of pregnancy may reveal the presence of genetic susceptibility to cardiovascular disease or accelerate the phenotypic expression of both inherited and acquired heart diseases, such as peripartum cardiomyopathy (PPCM). PPCM is a rare and incompletely understood clinical condition. Despite recent advances in the understanding of its pathogenesis, PPCM is not attributable to a well-defined pathological mechanism, and therefore, its diagnosis still relies on the exclusion of overlapping dilated phenotypes. Cardiac imaging plays a key role in any peripartum woman with signs and symptoms of heart failure in establishing the diagnosis, ruling out life-threatening complications, guiding therapy and conveying prognostic information. Echocardiography represents the first-line imaging technique, given its robust diagnostic yield and its favorable cost-effectiveness. Cardiovascular magnetic resonance is a biologically safe high-throughput modality that allows accurate morpho-functional assessment of the cardiovascular system in addition to the unique asset of myocardial tissue characterization as a pivotal piece of information in the pathophysiological puzzle of PPCM. In this review, we will highlight current evidence on the role of multimodality imaging in the differential diagnosis, prognostic assessment, and understanding of the pathophysiological basis of PPCM.

[Intravascular ultrasound-guided antegrade recanalization of a complex chronic total occlusion of the left anterior descending coronary artery: a case report]. / Disostruzione anterograda di complessa occlusione cronica totale del ramo interventricolare anteriore guidata dall'ecografia intravascolare: caso clinico.

Patients with coronary chronic total occlusion (CTO) if symptomatic for angina or with extensive inducible ischemia at provocative tests may be revascularized percutaneously or surgically. Percutaneous revascularization can be performed by antegrade or retrograde approach. In our case, in the presence of a long CTO of the left anterior descending coronary artery, the antegrade approach was chosen using an intravascular ultrasound (IVUS) catheter positioned in a secondary branch, to accurately identify the proximal lesion cap. IVUS is useful for selecting the appropriate stent size and length to ensure lesion coverage and stent optimization and to detect related complications.

Surgical bleeding after pre-operative unfractionated heparin and low molecular weight heparin for coronary bypass surgery.

BACKGROUND AND OBJECTIVES: Since the impairment of platelet function may cause excess peri-operative bleeding, pre-operative discontinuation of aspirin and heparin bridging are common for cardiac surgery. We evaluated the impact of pre-operative administration of enoxaparin and unfractionated heparin (UFH) on coagulation parameters and peri-operative bleeding in patients undergoing elective coronary artery bypass grafting (CABG) surgery after discontinuation of aspirin. DESIGN AND METHODS: Forty-three patients with three-vessel coronary artery disease undergoing elective CABG surgery discontinued aspirin and were randomized to receive either UFH 180 UI/Kg x 2/day s.c. or enoxaparin 100 UI/Kg x 2/day s.c. until 12 h before surgery (median pre-operative treatment 8 days, range 6-12 days). Surgery was performed as usual with UFH. Neither UFH nor any low molecular weight heparin was given in the immediate post-operative period. The effects of UFH and enoxaparin were monitored by the activated partial thromboplastin time (aPTT) and the Enox-test (sensitive to factor Xa inhibition) using a Rapidpoint Coagulation Analyzer. aPTT and factor Xa activity were also measured by standard methods. Peri-operative bleeding and the nadirs of hemoglobin concentration, hematocrit and platelet count were monitored post-operatively. RESULTS: Patients in the two groups were similar for number of bypasses, on-pump time, total surgery time, and time from the last heparin administration. Coagulation parameters increased significantly and similarly at 30 min and 6 h with both treatments, but returned within the normal range at 12 h. Hemoglobin, hematocrit and platelet counts significantly decreased to the same extent after CABG and re-normalized at the same time. Transfusional requirements of blood and plasma units were similar in the two groups. INTERPRETATION AND CONCLUSIONS: From the kinetics of coagulation parameters and the evaluation of bleeding, enoxaparin is a safe alternative to UFH as a bridging therapy to CABG after discontinuation of aspirin.

Aspirin overprescription in primary cardiovascular prevention.

INTRODUCTION: Aspirin overprescription is of some concern, especially in still-healthy individuals, and estimates of the magnitude of this problem are lacking. We evaluated the inappropriateness of aspirin prescription by primary care physicians in primary cardiovascular prevention. MATERIALS AND METHODS: Out of 20,599 patients screened by 16 primary care physicians in the Abruzzi region, central Italy, 400 patients were on treatment with aspirin for primary prevention. For each such patient, the absolute cardiovascular and coronary risks were assessed according to the Italian Cardiovascular Risk Chart for Primary Prevention and the European Society of Cardiology Coronary Risk Chart, respectively. Patients with a cardiovascular and/or coronary risk <1.0 event/100 patients/year were considered as treated inappropriately (aspirin overprescription), on the basis of previous literature. RESULTS: Overall, as many as 12% and 18% of patients had a cardiovascular and/or coronary risk <1.0 event/100 patients/year according to the European and the Italian charts, respectively, and therefore were defined as treated inappropriately. Patients with and without inappropriate treatment were similar with respect to smoking habits, family history and body max index. However, inappropriately treated patients had significantly lower levels of blood pressure and total cholesterol, and were more likely to be female, younger and non-diabetic than patients appropriately treated. CONCLUSIONS: A non-negligible proportion-up to 18%-of subjects in primary prevention is currently more likely to derive harm than benefit from inappropriate aspirin use. A wider use of Cardiovascular Risk Charts should guide primary care physicians in prescribing aspirin for primary prevention.

Spontaneous coronary artery dissection in a young woman resolved with conservative strategy. A case report.

Spontaneous coronary artery dissection (SCAD) is a rare disease associated with high mortality rate, whose etiology and pathogenesis has been poorly understood to date. The management of these patients is still controversial. A young, otherwise healthy woman, without known underlying conditions leading to SCAD, was admitted to our Intensive Cardiology Care Unit; she had history of intense psychological stress. She was managed with a conservative approach based on watchful waiting and medical therapy. She had an uneventful course. This is a rare case of SCAD where stable hemodynamics allowed us to adopt a conservative approach. .

Unexplained Cardiac Arrest After Near Drowning in a Young Experienced Swimmer: Insight from Cardiovascular Magnetic Resonance Imaging.

Cardiac magnetic resonance imaging (cMRI) is a well-established noninvasive imaging modality in clinical cardiology. Its ability to provide tissue characterization make it well suited for the study of patients with cardiac diseases. We describe a multi-modality imaging evaluation of a 45-year-old man who experienced a near drowning event during swimming. We underline the unique capability of tissue characterization provided by cMRI, which allowed detection of subtle, clinically unrecognizable myocardial damage for understanding the causes of sudden cardiac arrest and also showed the small damages caused by cardiopulmonary resuscitation.