[ANMCO/SIC Consensus statement on pulmonary arterial hypertension]. / Documento di consenso ANMCO/SIC sull'ipertensione arteriosa polmonare.

Pulmonary hypertension (PH) is a frequent pathological condition worldwide, mainly secondary to cardiovascular and respiratory diseases, with a poor prognosis. Pulmonary arterial hypertension (PAH) is a rare form that affects the arterial pulmonary vasculature. PH and PAH are characterized by non-specific symptoms and a progressive increase of pulmonary vascular resistance that results in progressive, sometimes irreversible, right ventricular dysfunction. In recent years, a growing medical and social commitment on this disease allowed more accurate diagnosis in shorter times. However, the gap between guidelines and clinical practice remains a challenge for all medical doctors involved in the disease management. Considering the needs to share and describe diagnostic and therapeutic pathways, to measure the results obtained and to address the economical and organizational problems of this disease, all involved figures should collaborate to improve its prognostic impact and health expenses. In this consensus document, the PH experts of the Italian Association of Hospital Cardiologists (ANMCO) together with those of the Italian Society of Cardiology (SIC), address 1) definition, classification and unmet needs of PH and PAH; 2) classification and characteristics of centers involved in the diagnosis and treatment of the disease; 3) proposal of organization of a diagnostic-therapeutic pathway, based on robust and recent scientific evidence.

[Pulmonary hypertension associated with left heart diseases: pathophysiology, diagnosis, treatment]. / Ipertensione polmonare associata ad insufficienza cardiaca: fisiopatologia, diagnosi, terapia.

Pulmonary hypertension (PH) is a common complication of diseases affecting the left heart, mostly found in patients suffering from heart failure. Left atrial hypertension is the initial driver of post-capillary PH. However, several mechanisms may lead in a subset of patients to structural changes in the pulmonary vessels with development of a pre-capillary component. The right ventricle may be frequently affected, leading to right ventricular failure and a worse outcome. The differential diagnosis of PH associated with left heart disease vs pulmonary arterial hypertension (PAH) is challenging in patients with cardiovascular comorbidities, risk factors for PAH and/or a preserved left ventricular ejection fraction. Multidimensional clinical phenotyping is needed to identify patients in whom hemodynamic confirmation is deemed necessary, that may be completed by provocative testing in the cath lab. In contrast with PAH, management of PH associated with left heart disease should focus on the treatment of the underlying condition. There is currently no approved therapy for PH associated with left heart disease: some PAH-specific treatments have led to an increase in adverse events in these patients.

Contemporary anticoagulant treatment strategies in patients with acute pulmonary embolism at different risk for death.

INTRODUCTION: Availability of new treatment strategies for patients with acute pulmonary embolism (PE) have changed clinical practice with potential influence in short-term patients' outcomes. We aimed at assessing contemporary anticoagulation strategies and mortality in patients with acute PE included in the prospective, non-interventional, multicentre, COntemporary management of PE study. MATERIALS AND METHODS: Anticoagulant treatment at admission, during hospital-stay, at discharge and at 30-day are described in the overall population and by clinical severity. RESULTS: Overall, 5158 patients received anticoagulant treatment (99%); during the hospital-stay, 2298 received completely parenteral, 926 completely oral and 1934 parenteral followed by oral anticoagulation (1670 DOACs, 264 VKAs). Comorbidities and PE severity influenced the choice of in-hospital anticoagulation. The use of completely parenteral and completely oral anticoagulation varied based on PE severity. In patients treated with thrombolysis, DOACs were used in 46.4% and 80.1% during the hospital stay and at discharge, respectively. Death at 30 days occurred in 34.6% of patients not receiving anticoagulant treatment and in 1.5, 1.3, 3.4 and 8.1% of patients receiving completely oral, sequential with DOACs, sequential with VKAs and completely parenteral regimens, respectively. Increased mortality in patients receiving completely parenteral anticoagulation persisted after adjustment for PE severity. Completely oral anticoagulation was effective and safe also in patients at intermediate-high risk of death. CONCLUSIONS: Contemporary anticoagulation for acute PE includes parenteral agents in over 90% of patients; DOACs are used in the large majority of PE patients at discharge and their early use seems effective and safe also in selected intermediate-risk patients. TRIAL REGISTRATION NUMBER: NCT03631810.

Efficacy and Safety of Anticoagulant Therapy in COVID-19-Related Pulmonary Embolism with Different Extension.

Pulmonary embolism (PE) has been associated with SARS-CoV-2 infection, and its incidence is highly variable. The aim of our study was to describe the radiological and clinical presentations, as well as the therapeutic management, of PEs that occurred during SARS-CoV-2 infection in a cohort of hospitalized patients. In this observational study, we enrolled patients with moderate COVID-19 who developed PE during hospitalization. Clinical, laboratory, and radiological features were recorded. PE was diagnosed on clinical suspicion and/or CT angiography. According to CT angiography results, two groups of patients were further distinguished: those with proximal or central pulmonary embolism (cPE) and those with distal or micro-pulmonary embolism (mPE). A total of 56 patients with a mean age of 78 ± 15 years were included. Overall, PE occurred after a median of 2 days from hospitalization (range 0-47 days) and, interestingly, the majority of them (89%) within the first 10 days of hospitalization, without differences between the groups. Patients with cPE were younger (p = 0.02), with a lower creatinine clearance (p = 0.04), and tended to have a higher body weight (p = 0.059) and higher D-Dimer values (p = 0.059) than patients with mPE. In all patients, low-weight molecular heparin (LWMH) at anticoagulant dosage was promptly started as soon as PE was diagnosed. After a mean of 16 ± 9 days, 94% of patients with cPE were switched to oral anticoagulant (OAC) therapy, which was a direct oral anticoagulant (DOAC) in 86% of cases. In contrast, only in 68% of patients with mPE, the prosecution with OAC was indicated. The duration of treatment was at least 3 months from PE diagnosis in all patients who started OAC. At the 3-month follow-up, no persistence or recurrence of PE as well as no clinically relevant bleedings were found in both groups. In conclusion, pulmonary embolism in patients with SARS-CoV-2 may have different extensions. Used with clinical judgment, oral anticoagulant therapy with DOAC was effective and safe.

[Anticoagulation therapy during pulmonary embolism follow-up in clinical practice]. / Gestione della terapia anticoagulante nel follow-up dell'embolia polmonare nella pratica clinica.

Patients with pulmonary embolism are a heterogeneous population and, after the acute phase and the first 3-6 months, the main issue is whether to continue, and hence how long and at what dose, or to stop anticoagulation therapy. In patients with venous thromboembolism (VTE), direct oral anticoagulants (DOACs) are the recommended treatment (class I, level of evidence B in the latest European guidelines), and in most cases, an "extended" or "long-term" low-dose therapy is warranted. This paper aims to provide a practical management tool to the clinician dealing with pulmonary embolism follow-up: from the evidence behind the most used exams (D-dimer, ultrasound Doppler of the lower limbs, imaging tests, recurrence and bleeding risk scores), and the use of DOACs in the extended phase, to six real clinical scenarios with the relative management in the acute phase and at follow-up. Lastly, a practical algorithm is shown to deal with anticoagulation therapy in the follow-up of VTE patients in a simple, schematic, and pragmatic way.

Prognostic Impact of New-Onset Atrial Fibrillation After Single or Double Stent Left Main Bifurcation PCI.

OBJECTIVE: Incidence and prognostic value of new-onset atrial fibrillation after single versus double stent strategy in bifurcation left main disease has not been yet investigated. METHODS: We retrospectively analyzed the procedural and medical data of patients referred to our center for complex left main bifurcation disease, treated using crossover provisional stenting, T or T-and-Protrusion, Culotte, and Nano-inverted-T techniques between January 1, 2008, and May 1, 2018. Multivariate Cox-regression analysis was used to assess the role of different stent strategies, adjusted for confounders, on the risk of new-onset atrial fibrillation during the follow-up period. RESULTS: Five hundred two patients (316 males, mean age 70.3 ± 12.8 years, mean Syntax score 31.6 ± 6.3) were evaluated. At a mean follow-up of 37.1 ± 10.8 months (range: 22.1- 39.3 months); Target lesion failure rate was 10.1%. Stent thrombosis and cardiovascular mor- tality were observed in 1.2% and 3.6% in of cases, respectively. New-onset atrial fibrillation occurred in 23 out of 502 patients (4.6%). Patients with new-onset atrial fibrillation resulted more frequently female, older, obese, and diabetic and more frequently experienced target lesion failure and cardiovascular death. New-onset atrial fibrillation-free survival favored single versus double stent technique and among double stent techniques nano-inverted-T tech- niques compared to the others. Single stent strategy had a lower risk of new-onset atrial fibril- lation compared to double stent technique on multivariate analysis (Hazard Ratio (HR): 1.14, 95% CI: 1.10-1.19, P < .001 vs. HR: 1.28, 95% CI: 1.23-1.32, P < .0001). CONCLUSION: New-onset atrial fibrillation in distal left main bifurcation disease treated with per- cutaneous coronary intervention had a low incidence but resulted more frequently after double than after single stenting technique and was associated with worse outcomes.

[Pulmonary hypertension: pre- or post-capillary? The role of provocative tests in the cath lab]. / Ipertensione polmonare pre-capillare o post-capillare? Il ruolo dei test provocativi in sala di emodinamica.

The discrimination between heart failure with preserved ejection fraction (HFpEF) and pulmonary arterial hypertension (PAH) requires a multiparametric approach, eventually culminating in right heart catheterization. Solving this differential diagnosis is crucial in order to properly tailor patient treatment, with relevant clinical implications. However, it is not uncommon to be confronted with patients at intermediate or high risk of having HFpEF whose pulmonary artery wedge pressure (PAWP) falls in a grey zone in between 13 and 15 mmHg. In these patients, a provocative test in the cath lab might be considered, with the aim of unmasking an occult form of HFpEF with non-overt hemodynamic manifestations, or to definitely exclude it.Saline load and physical exercise can be viewed as the most suitable provocative tests seeking to help for the differential diagnosis in this specific patient population. Although normative values for the hemodynamic response to these maneuvers have been proposed, supporting evidence is still preliminary or equivocal. In this paper, we will review the pathophysiological background for the application of provocative tests in the cath lab, as well as methodological and interpretative aspects to discriminate between HFpEF and PAH, highlighting strengths and weaknesses of fluid load and physical exercise.

Gender-related differences in clinical outcomes after either single or double left main bifurcation stenting.

We sought to examine the impact of gender differences in clinical outcomes at 3 years also comparing the role of double versus single stenting approach for the treatment of coronary unprotected LM bifurcation lesions. We retrospectively analyzed both the procedural and medical data of patients referred to our hub center for complex LM bifurcation disease, treated using Crossover provisional stenting, T or T-and-Protrusion (TAP), Culotte, and Nano-inverted-T (NIT) techniques between January 1st, 2008 and May 1st 2018. The main outcome of the study was to evaluate the association between gender and target lesion failure (TLF) based on the different stenting technique used. Five hundred and sixty-seven patients (251 females, mean age 70.0 ± 10 years, mean Syntax score 31.6 ± 6.3) were evaluated. Crossover, T or TAP, culotte and NIT techniques were performed in 171 (30.1%), 61 (10.7%), 98 (17.2%) and 237 (41.8%) patients, respectively with no differences in baseline and peri-procedural items among gender. At a mean follow-up of 37.1 ± 10.8 months (range 22.1-39.3 moths), the overall TLF rate, cardiovascular mortality and stent thrombosis were 12.1%, 3.1% and 1.0%, respectively. Female gender was associated with an increased rate of major bleeding when treated with double stent strategy (p = 0.02). No gender difference in TLF was noted among gender, independently from the stenting approach used. Among patients with ULM bifurcation disease undergoing PCI, TLF rates were not different between genders at 3-year follow-up either using a single or double stent technique.

Ultrathin Biodegradable-Polymer Orsiro Drug-Eluting Stent Performance in Real Practice Challenging Settings.

BACKGROUND: The Orsiro cobalt-chromium stent platform (Biotronik, Bülach, Switzerland) is one of the first devices in the era of ultrathin struts. However, data regarding the efficacy of Orsiro stent in patients with challenging anatomical conditions obtained from daily clinical practice are scant. METHODS: We retrospectively reviewed the long-term outcomes, defined as target lesion revascularization (TLR), target vessel revascularization (TVR), stent thrombosis (ST) and cardiovascular (CV) mortality over a six years period, in 1161 consecutive patients (mean age 64.3 ± 11.2 years old, 681 males) treated with 2327 Orsiro stents in our institution who presented with challenging anatomic/angiographic features. RESULTS: The mean number of implanted stents was 1.7 ± 2.1 whereas the mean stent diameter and length were 3.6 ± 1.1 and 32.7 ± 15.6 mm, respectively. Mean follow-up duration was 35.6 ± 17 months (range 1-77 months); 923 patients (79.5%) reached the 3-year follow-up. The global rates of TLR, TVR, ST and CV mortality were 0.1%, 1.37%, 0.002%, and 1.9%, respectively with scarce statistically significant differences in multivessel disease, severe calcification, and lesion length > 41 mm. Multivariate regression analysis revealed that age, stent dislodgement, early stent thrombosis (p = 0.001) and lesion length ≥ 41 mm (p = 0.001) were independent predictors of TVR. Similarly, the occurrence of TLR was independently predicted by age, severe calcification, use of IVUS and Rotablator (p = 0.002), early stent thrombosis, LM bifurcation and length ≥ 41 mm (p = 0.001). CONCLUSIONS: The Orsiro stent confirmed a very high efficacy profile in all anatomical scenarios with very low rates of clinically driven TLR and TVR, CV mortality and ST at 3-years.

[ANMCO Position paper: Pulmonary circulation diseases and COVID-19]. / Position paper ANMCO: Malattie del circolo polmonare e COVID-19.

The new coronavirus disease 2019 (COVID-19), which is causing hundreds of thousands of deaths worldwide, is complex and can present with a multi-organ localization. One of its worst complications is an interstitial pneumonia with acute respiratory failure also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which requires non-invasive or invasive ventilation. A severe coagulopathy with poor prognosis is found in 5-10% of cases. SARS-CoV-2 is manifesting as a multi-dimensional disease and, recently, unique co-existing pathophysiological and clinical aspects are being defined: (i) an increased immune and inflammatory response with the activation of a cytokine storm and consequent coagulopathy, which promote both venous thromboembolic events and in situ thrombosis localized in small arterioles and pulmonary alveolar capillaries; (ii) a high intrapulmonary shunt, which often accounts for the severity of respiratory failure, due to reduced hypoxic pulmonary vasoconstriction with pulmonary neo-angiogenetic phenomena. Furthermore, the high incidence of venous thromboembolism in COVID-19 patients admitted to the intensive care unit and the autoptic findings of in situ micro-thrombosis at the pulmonary vascular level, suggest that in this disease coagulopathy, unlike septic disseminated intravascular coagulation, is driven towards a hyper-thrombogenic state, giving rise to a debate (with ongoing studies) about the preventive use of anticoagulant doses of heparin to reduce mortality. The aim of this position paper from the Italian Association of Hospital Cardiologists (ANMCO) is to highlight the main implications that COVID-19 infection has on the pulmonary circulation from a pathophysiological, clinical and management point of view.

[Proposal for a standardized discharge letter after hospital stay for acute pulmonary embolism]. / Proposta di una lettera di dimissione standardizzata dopo ospedalizzazione per embolia polmonare acuta.

Pulmonary embolism represents the third leading cause of cardiovascular mortality in developed countries. It requires, in most cases, hospital treatment and always a structured follow-up program. Therefore, at the time of discharge, the communication and the transfer of information from the specialist to the general practitioner, through the discharge letter, represents a crucial opportunity. The aim is to improve the quality of the transmitted content, including information regarding initial assessment, procedures during hospitalization, residual risks, discharge treatments, therapeutic goals and follow-up plan in accordance with the latest guidelines. The discharge letter after hospitalization for pulmonary embolism must include personalized information, especially regarding the anticoagulant regimen in the specific onset setting. Finally, the follow-up program should be accurately described. A standardized discharge letter template, accompanied by some final notes addressed to the general practitioner and patient, could represent a useful tool to improve the quality and time of transmission of information between health professionals after pulmonary embolism.

Risk of Dislodgement of Ultrathin Drug Eluting Stents Versus Thick Drug Eluting Stents.

Modern ultrathin struts drug eluting stents (DES), due to their constructive characteristics, might be more prone to stent dislodgment than the old thick DES. Our study is aimed to retrospectively analyze and compare the incidence and outcomes of stents dislodgment in thick (TSS) and ultrathin strut stents (USS).We retrospectively analyzed the procedural and medical data of 8,564 consecutive patients (mean age 64.3 ± 11.2 years old, 4442 males) who underwent percutaneous coronary intervention with DES implantation in our Institution between 1st January 2005 to 1st January 2020. Overall, 25,692 (mean of 3.2 stent for patients) have been implanted over the study period (10648 TSS and 15044 and USS, respectively). Stent dislodgment globally occurred in 0.56% of the implanted stents (0.28% vs 0.78%, p <0.001 for TTS and USS, respectively). Coronary artery calcifications, ostial lesion, coronary artery tortuosity, and a lesion length >25 mm were independent predictors of type I and II USS dislodgments. At 12 months follow up, the rate of target lesion failure was higher in the TTS group (30.7 vs 12.7 %, p <0.001). Stent dislodgement is unusual in the modern era but is more frequent using USS than TTS DES.

[Diagnostic and therapeutic models for the management of acute pulmonary embolism: an issue of local available resources]. / Modelli diagnostici e terapeutici nel trattamento dell'embolia polmonare acuta: una questione di risorse locali.

Acute pulmonary embolism (PE) still represents the third leading cause of cardiovascular mortality in developed countries. In this regard, the last European guidelines offer important suggestions on the management of the disease in daily clinical practice but, at the same time, they do not take into account the feasibility of the recommendations according to the local available resources, including the presence or lack of adequate healthcare facilities (cardiological intensive care unit, cath-lab) or specialists (cardiologist available on a 24 h basis, interventional cardiologist, cardiac surgeon, etc.) all over the day. In the real clinical practice, those recommendations should be adapted to the local available resources. The aim of this document is to provide some suggestions regarding the diagnosis and treatment of acute PE, according to the possible available resources in different local circumstances.

The QR-max index, a novel electrocardiographic index for the determination of left ventricular conduction delay and selection of cardiac resynchronization in patients with non-left bundle branch block.

Non-left bundle branch block (non-LBBB) remains an uncertain indication for cardiac resynchronization therapy (CRT). Non-LBBB includes right bundle branch block (RBBB) and non-specific LV conduction delay (NSCD), two different electrocardiogram (ECG) patterns which are not generally considered to be associated with LV conduction delay as judged by the invasive assessment of the Q-LV interval. We evaluated whether a novel ECG interval (QR-max index) correlated with the degree of LV conduction delay regardless of the type of non-LBBB ECG pattern, and could, therefore, predict CRT response. In 173 non-LBBB patients on CRT (92 NSCD, 81 RBBB), the QR-max index was measured as the maximum interval from QRS onset to R-wave offset in the limb leads. The correlation between QR-max index and Q-LV interval and the impact of the QR-max index on time to first heart failure hospitalization during 3-year follow-up were assessed. Q-LV correlated better with the QR-max index than with QRSd, particularly in the RBBB group (r = 0.91; p < 0.001 vs. r = 0.19; p < 0.089), while the correlations were r = 0.79 (p < 0.01) and r = 0.68 (p < 0.01), respectively, in the NSCD group. In both groups, the QR-max index was significantly more able than QRSd to identify CRT responders (AUC 0.825 vs. 0.576; p = 0.0008 in RBBB; AUC 0.738 vs. 0.701; p = 0.459 in NSCD). A QR-max index exceeding a cutoff value of 120 ms was associated with CRT response, with predictive values of 86.8 and 81.4% in RBBB and NSCD, respectively. The QR-max index reflects the degree of LV electrical delay regardless of QRS duration in RBBB and NSCD patients and is a useful indicator of suitability for CRT in non-LBBB patients.

[ANMCO statement: Arterial and venous thromboembolism: what implications for clinical practice?] / Statement ANMCO: Tromboembolismo arterioso e venoso: quali implicazioni per la pratica clinica?

Acute myocardial infarction, stroke, peripheral arterial disease and pulmonary embolism share thrombosis as a common mechanism. Some well-known risk factors for arterial thromboembolism are recognized as "weak risk factors" of venous one, too. Arterial and venous thrombosis share also some pathophysiological mechanisms, including inflammation, endothelial damage, and hypercoagulability. It is likely, thus, that any disease related to arterial and venous thrombosis belong to the same "pan-vascular syndrome", that constitutes itself a chronic, recurrent inflammatory disease. According to the available data, there are elements for implementing an omni-comprehensive cardiovascular evaluation after an episode of venous thromboembolism, requiring the investigations, in addition to the known unrecognized prothrombotic conditions, also of indirect signs and risk factors for a possible arterial thromboembolic event. Large, prospective studies are needed to establish the more appropriate therapeutic strategies in this context.The aim of the present statement is to make aware all the physicians involved in the management of arterial and venous diseases and to provide some tools for evaluating the implications of related major risk factors. Thus, it could be possible to lay the foundation for a reduction of total cardiovascular risk, in terms of primary and secondary prevention of arterial and venous thromboembolism.

Hemodynamic comparison of different multisites and multipoint pacing strategies in cardiac resynchronization therapies.

PURPOSE: In order to increase the responder rate to CRT, stimulation of the left ventricular (LV) from multiple sites has been suggested as a promising alternative to standard biventricular pacing (BIV). The aim of the study was to compare, in a group of candidates for CRT, the effects of different pacing configurations-BIV, triple ventricular (TRIV) by means of two LV leads, multipoint (MPP), and multipoint plus a second LV lead (MPP + TRIV) pacing-on both hemodynamics and QRS duration. METHODS: Fifteen patients (13 male) with permanent AF (mean age 76 ± 7 years; left ventricular ejection fraction 33 ± 7%; 7 with ischemic cardiomyopathy; mean QRS duration 178 ± 25 ms) were selected as candidates for CRT. Two LV leads were positioned in two different branches of the coronary sinus. Acute hemodynamic response was evaluated by means of a RADI pressure wire as the variation in LVdp/dtmax. RESULTS: Per patient, 2.7 ± 0.7 veins and 5.2 ± 1.9 pacing sites were evaluated. From baseline values of 998 ± 186 mmHg/s, BIV, TRIV, MPP, and MPP-TRIV pacing increased LVdp/dtmax to 1200 ± 281 mmHg/s, 1226 ± 284 mmHg/s, 1274 ± 303 mmHg, and 1289 ± 298 mmHg, respectively (p < 0.001). Bonferroni post-hoc analysis showed significantly higher values during all pacing configurations in comparison with the baseline; moreover, higher values were recorded during MPP and MPP + TRIV than at the baseline or during BIV and also during MPP + TRIV than during TRIV. Mean QRS width decreased from 178 ± 25 ms at the baseline to 171 ± 21, 167 ± 20, 168 ± 20, and 164 ± 15 ms, during BIV, TRIV, MPP, and MPP-TRIV, respectively (p < 0.001). CONCLUSIONS: In patients with AF, the acute response to CRT improves as the size of the early activated LV region increases.

A prospective validation of the Bova score in normotensive patients with acute pulmonary embolism.

BACKGROUND: The Bova score has shown usefulness in the identification of intermediate-high risk patients with acute pulmonary embolism (PE), but lacks prospective validation. The aim of this study was to prospectively validate the Bova score in different settings from the original derivation cohort. METHODS: Consecutive, normotensive patients with acute PE recruited at 13 academic or general hospitals were stratified, using their baseline data, into the three Bova risk stages (I-III). The primary outcome was the 30-day composite of PE-related mortality, hemodynamic collapse and non-fatal PE recurrences in the three risk categories. RESULTS: In the study period, 639 patients were enrolled. The primary end point occurred in 45 patients (7.0%; 95% Confidence Intervals, 5.2%-9.3%). Risk stage correlated with the PE-related complication rate (stage I, 2.9%; stage II, 17%; stage III, 27%). Patients classified as stage III by the Bova score had a 6.5-fold increased risk for adverse outcomes (3.1-13.5, p < 0.001) compared with stages I and II combined. Rescue thrombolysis increased from stage I to stage III (0.6%, 12% and 15% respectively). All-cause mortality (5.3%) did not substantially differ among the stages. CONCLUSIONS: The Bova score accurately stratifies normotensive patients with acute PE into stages of increasing risk of 30-day PE-related complications.