The paradox of pulmonary arterial hypertension in Italy in the COVID-19 era: is risk of disease progression around the corner?

OBJECTIVE: The coronavirus disease 2019 (COVID-19) outbreak has led to significant restrictions on routine medical care. We conducted a multicentre nationwide survey of patients with pulmonary arterial hypertension (PAH) to determine the consequences of governance measures on PAH management and risk of poor outcome in patients with COVID-19. MATERIALS AND METHODS: The present study, which included 25 Italian centres, considered demographic data, the number of in-person visits, 6-min walk and echocardiographic test results, brain natriuretic peptide/N-terminal pro-brain natriuretic peptide test results, World Health Organization functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates. Data were collected, double-checked and tracked by institutional records between March 1 and May 1, 2020, to coincide with the first peak of COVID-19 and compared with the same time period in 2019. RESULTS: Among 1922 PAH patients, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 were 1.0% and 0.46%, respectively, with the latter comparable to that in the overall Italian population (0.34%) but associated with 100% mortality. Less systematic activities were converted into more effective remote interfacing between clinicians and PAH patients, resulting in lower rates of hospitalisation (1.2% versus 1.9%) and related death (0.3% versus 0.5%) compared with 2019 (p<0.001). A high level of attention is needed to avoid the potential risk of disease progression related to less aggressive escalation of treatment and the reduction in new PAH diagnoses compared with 2019. CONCLUSION: A cohesive partnership between healthcare providers and regional public health officials is needed to prioritise PAH patients for remote monitoring by dedicated tools.

Removal of an active fixation coronary sinus pacing lead 5 years postimplant: A case report.

Active fixation for a lead in the coronary sinus may be essential to select the optimal left ventricular pacing site, maximize the effectiveness of cardiac resynchronization therapy (CRT) and avoid dislodgement. The Medtronic Attain Stability lead allows fixation through a side helix concentric with the lead body. Although electrical performance of such a lead is well known, evidence of extractability remains poor especially in the long term. We describe the removal of an Attain Stability lead 63 months after implantation which, to the best of our knowledge, is the longest implant duration that has ever been reported, in an 81-year-old male patient. It was successfully achieved using simple traction and rotation maneuvers, demonstrating the long-term removal feasibility of such device.

Risk Reduction and Hemodynamics with Initial Combination Therapy in Pulmonary Arterial Hypertension.

Rationale: An initial oral combination of drugs is being recommended in pulmonary arterial hypertension (PAH), but the effects of this approach on risk reduction and pulmonary vascular resistance (PVR) are not known.Objectives: To test the hypothesis that a low-risk status would be determined by the reduction of PVR in patients with PAH treated upfront with a combination of oral drugs.Methods: The study enrolled 181 treatment-naive patients with PAH (81% idiopathic) with a follow-up right heart catheterization at 6 months (interquartile range, 144-363 d) after the initial combination of endothelin receptor antagonist + phosphodiesterase-5 inhibitor drugs and clinical evaluation and risk assessments by European guidelines and Registry to Evaluate Early and Long-Term PAH Disease Management scores.Measurements and Main Results: Initial combination therapy improved functional class and 6-minute-walk distance and decreased PVR by an average of 35% (median, 40%). One-third of the patients had a decrease in PVR <25%. This poor hemodynamic response was independently predicted by age, male sex, pulmonary artery pressure and cardiac index, and at echocardiography, a right/left ventricular surface area ratio of greater than 1 associated with low tricuspid annular plane systolic excursion of less than 18 mm. A low-risk status at 6 months was achieved or maintained in only 34.8% (Registry to Evaluate Early and Long-Term PAH Disease Management score) to 43.1% (European score) of the patients. Adding criteria of poor hemodynamic response improved prediction of a low-risk status.Conclusions: A majority of patients with PAH still insufficiently improved after 6 months of initial combinations of oral drugs is identifiable at initial evaluation by hemodynamic response criteria added to risk scores.

Remote assessment of QT interval: A new perspective for implantable cardiac monitors.

BACKGROUND: There is an unmet need for simple tools for monitoring QT intervals. The feasibility of measuring the QT interval on the single­lead subcutaneous electrocardiogram (subECG) recorded and transmitted by implantable cardiac monitors (ICMs) has never been tested. METHODS: We performed a standard ECG in patients who had already been implanted with a long sensing vector ICM (BIOMONITOR, Biotronik SE&Co.) to calculate the corrected QT interval in lead II (QTc ECG). The QTc was then evaluated on the subECG provided by ICM both by using the programmer printout (QTc subECG) and the snapshot transmitted via home monitoring (QTc HM). Values were compared with Bland-Altman analyses. RESULTS: The study cohort consisted of 23 ICM recipients (age 58 ± 19 years, 35% female) implanted mainly for unexplained syncope (78%). The mean QTc ECG interval was 404 ± 31 ms. The T-wave was visible and QTc could be calculated in all patients using the ICM programmer printout and in 21 (91%) patients remotely. The QTc subECG and QTc HM were 405 ± 34 and 406 ± 32 ms. Compared to the QTc ECG, Bland-Altman analyses revealed a bias of -0.9 (95% confidence interval: -6.8/4.9) ms and 0.1 (-12.7/12.9) ms for QTc subECG and QTc HM, respectively. CONCLUSIONS: The QTc interval can be reliably estimated on in-person and remote subECG in most patients without bias compared to the ECG lead II assessment. This technology has the potential to facilitate remote QT interval monitoring.

Authors' response to the Letter to the Editor regarding: Post severe COVID-19 infection lung damages study. The experience of early three months multidisciplinary follow-up.

To the Editor, we thank Dr Ruggeri et al. for their interest in our previously published manuscript focused on lung damages after severe respiratory COVID-19 infection...

Post severe COVID-19 infection lung damages study. The experience of early three months multidisciplinary follow-up.

The correct type and time of follow-up for patients affected by COVID19 ARDS is still unclear. The aim of this study was to evaluate at the survivors to COVID19 ARDS requiring non-invasive respiratory support (NRS) admitted to a Respiratory Intensive care unit (RICU) from March 8th till May 31th 2020 looking at all sequelae via a comprehensive follow up. All patients underwent a multi-disciplinary instrumental and clinical assessment within three months form admission to evaluate all infection related sequelae. Thirty-eight patients were enrolled Lung-Ultrasound (LUS) showed an outstanding discrimination ability (ROC AUC: 0.95) and a substantial agreement rate (Cohen's K: 0.74) compared to chest CT-scan detecting improvement of lung consolidations. Youden's test showed a cut-off pressure of 11 cmH2O ExpiratoryPAP-Continuous-PAP-max (EPAP-CPAP) applied at the airways during hospitalization to be significantly correlated (p value: 0.026) to the increased pulmonary artery common trunk diameter. A total of 8/38 patients (21.8%), 2 of whom during follow-up, were diagnosed with Pulmonary Emboli (PE) and started anticoagulant treatment. Patients with PE had a statistically significant shorter length of time of hospitalization, time to negative swab, CPAP/NIV duration, P/F ratio and D-dimers at follow-up compared to non PE. A comprehensive approach to patients with ARDS COVID19 requiring NRS is necessary. This study highlighted cardiopulmonary impairment related to the ARDS and to the high-EPAP-CPAP-max greater than 11mmHg provided during admission, the usefulness of LUS in monitoring post-infection recovery and the correct identification and  treatment of patients with PE during follow up.

Multipoint pacing via a quadripolar left-ventricular lead: preliminary results from the Italian registry on multipoint left-ventricular pacing in cardiac resynchronization therapy (IRON-MPP).

AIMS: This registry was created to describe the experience of 76 Italian centres with a large cohort of recipients of multipoint pacing (MPP) capable cardiac resynchronization therapy (CRT) devices. METHODS AND RESULTS: A total of 507 patients in whom these devices had been successfully implanted were enrolled between August 2013 and May 2015. We analysed: (i) current clinical practices for the management of such patients, and (ii) the impact of MPP on heart failure clinical composite response and on the absolute change in ejection fraction (EF) at 6 months. Multipoint pacing was programmed to 'ON' in 46% of patients before discharge. Methods of optimizing MPP programming were most commonly based on either the greatest narrowing of the QRS complex (38%) or the electrical delays between the electrodes (34%). Clinical and echocardiographic follow-up data were evaluated in 232 patients. These patients were divided into two groups according to whether MPP was programmed to 'ON' (n = 94) or 'OFF' (n = 138) at the time of discharge. At 6 months, EF was significantly higher in the MPP group than in the biventricular-pacing group (39.1 ± 9.6 vs. 34.7 ± 7.6%; P < 0.001). Even after adjustments, early MPP activation remained an independent predictor of absolute increase in LVEF of ≥5% (odds ratio 2.5; P = 0.001). At 6 months, an improvement in clinical composite score was recorded in a greater proportion of patients with MPP-ON than in controls (56 vs. 38%; P = 0.009). On comparing optimal MPP and conventional vectors, QRS was also seen to have decreased significantly (P < 0.001). CONCLUSION: This study provides information that is essential in order to deal with the expected increase in the number of patients receiving MPP devices in the coming years. The results revealed different practices among centres, and establishing the optimal programming that can maximize the benefit of MPP remains a challenging issue. Compared with conventional CRT, MPP improved clinical status and resulted in an additional increase in EF. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrial.gov/. Unique identifier: NCT02606071.

ANMCO Position Paper: the use of non-vitamin K dependent new oral anticoagulant(s) in pulmonary embolism therapy and prevention.

The new oral anticoagulants (NOACs) have radically changed the approach to the treatment and prevention of thromboembolic pulmonary embolism. The authors of this position paper face, in succession, issues concerning NOACs, including (i) their mechanism of action, pharmacodynamics, and pharmacokinetics; (ii) the use in the acute phase with the 'double drug single dose' approach or with 'single drug double dose'; (iii) the use in the extended phase with demonstrated efficacy and with low incidence of bleeding events; (iv) the encouraging use of NOACs in particular subgroups of patients such as those with cancer, the ones under- or overweight, with renal insufficiency (creatinine clearance > 30 mL/min), the elderly (>75 years); (v) they propose a possible laboratory clinical pathway for follow-up; and (vi) carry out an examination on the main drug interactions, their potential bleeding risk, and the way to deal with some bleeding complications. The authors conclude that the use of NOACs both in the acute phase and in the extended phase is equally effective to conventional therapy and associated with fewer major bleeding events, which make their use in patients at higher risk of recurrences safer.

ANMCO Position Paper: long-term follow-up of patients with pulmonary thromboembolism.

Venous thromboembolism (VTE), including pulmonary embolism and deep venous thrombosis, is the third most common cause of cardiovascular death. The management of the acute phase of VTE has already been described in several guidelines. However, the management of the follow-up (FU) of these patients has been poorly defined. This consensus document, created by the Italian cardiologists, wants to clarify this issue using the currently available evidence in VTE. Clinical and instrumental data acquired during the acute phase of the disease are the cornerstone for planning the FU. Acquired or congenital thrombophilic disorders could be identified in apparently unprovoked VTE during the FU. In other cases, an occult cancer could be discovered after a VTE. The main targets of the post-acute management are to prevent recurrence of VTE and to identify the patients who can develop a chronic thromboembolic pulmonary hypertension. Knowledge of pathophysiology and therapeutic approaches is fundamental to decide the most appropriate long-term treatment. Moreover, prognostic stratification during the FU should be constantly updated on the basis of the new evidence acquired. Currently, the cornerstone of VTE treatment is represented by both the oral and the parenteral anticoagulation. Novel oral anticoagulants should be an interesting alternative in the long-term treatment.