Relevance of comorbidities on initial combination therapy in pulmonary arterial hypertension.

Rationale: Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting. Methods: The study enrolled 181 treatment-naive PAH patients with a 6-month (IQR 144-363 days) right heart catheterisation and risk assessment after initial oral combination therapy. Results: Group A included 96 (53.0%) patients without cardiac comorbidities; Group B included 54 (29.8%) patients with one cardiac comorbidity; Group C included 31 (17.1%) patients with two cardiac comorbidities or more. Group C patients were older with a balanced sex distribution. There was a significant difference in PVR reduction moving from the absence to one or at least two cardiac comorbidities, respectively: median -45.0%, -30.3%, -24.3%. A European Respiratory Society/European Society of Cardiology low-risk status was present at first follow-up in 50 (52.0%) patients in Group A, 19 (35.1%) in Group B and 9 (29.0%) in Group C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group A, 15 (27.7%) in Group B and 7 (22.6%) in Group C. Group A patients were 2.3 times more likely to achieve/maintain a low-risk status compared with Group B and C (OR 2.27, 95% CI 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities. Conclusion: Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment-induced decrease in PVR.

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.

Chronic thromboembolic pulmonary hypertension risk score evaluation and validation (CTEPH SOLUTION): proposal of a study protocol aimed to realize a validated risk score for early diagnosis.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is the most serious long-term complication of acute pulmonary embolism (PE) though it is the only potentially reversible form of pulmonary hypertension (PH). Its incidence is mainly limited to the first 2 years following the embolic event, however it is often underdiagnosed or misdiagnosed. METHODS: This is a multicenter observational cross-sectional and prospective study. Patients with a prior diagnosis of PE will be enrolled and undergo baseline evaluation for prevalent PH detection through a clinical examination and an echocardiogram as first screening exam. All cases of intermediate-high echocardiographic probability of PH will be confirmed by right heart catheterization and then identified as CTEPH through appropriate imaging and functional examinations in order to exclude other causes of PH. A CTEPH Risk Score will be created using retrospective data from this prevalent cohort of patients and will be then validated on an incident cohort of patients with acute PE. RESULTS: One thousand retrospective and 218 prospective patients are expected to be enrolled and the study is expected to be completed by the end of 2021. Up to now 841 patients (620 retrospective and 221 prospective) have been enrolled. CONCLUSIONS: This study is the first large prospective study for the prediction of CTEPH development in patients with PE. It aims to create a comprehensive scoring tool that includes echocardiographic data which may allow early detection of CTEPH and the application of targeted follow-up screening programs in patients with PE.

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.

Echocardiographic score for prediction of pulmonary hypertension at catheterization: the Daunia Heart Failure Registry.

BACKGROUND: Right heart catheterization (RHC) is recommended by guidelines for the diagnosis of pulmonary hypertension, the definition of hemodynamic impairment and responsiveness to drug therapy. However, RHC is an invasive test with associated risk of complications. Noninvasive echocardiographic tools, possibly predictive of pulmonary hypertension at RHC, could be therefore extremely useful. METHODS: Sixty-four consecutive patients with suspected pulmonary hypertension were enrolled in the study and assessed by echocardiography and RHC. Diagnosis of pulmonary hypertension was based on mean pulmonary artery pressure (≥25 mmHg) at RHC. RESULTS: Of 64 consecutive patients enrolled, 77% were diagnosed as having pulmonary hypertension after RHC. On the basis of significant differences between patients with pulmonary hypertension at RHC and those without on echocardiographic assessment, a multiple logistic regression model was constructed to predict the presence of pulmonary hypertension at RHC. The score was calculated using right atrium and ventricular diastolic area, tricuspid regurgitation Vmax, tricuspid regurgitation severity degree and left ventricular ejection fraction. The score area under the curve was therefore 0.786 (P = 0.0001), higher than for tricuspid regurgitation Vmax (P = 0.06). A score value more than 57 was associated with a 93% sensitivity, a 67% specificity, a 91% positive predictive power, a 73% negative predictive power, and an odds ratio 27 (P < 0.001) of pulmonary hypertension at RHC, significant even after correction at multivariable analysis. Accuracy of the prediction model was assessed in a validation cohort with comparable results (P = n.s.). CONCLUSION: A simple noninvasive echocardiographic score can be useful in predicting the diagnosis of pulmonary hypertension at RHC and may be considered for the selection of patients who should undergo or could avoid RHC.

Lancisi's sign and central venous catheter tip position: a case report.

INTRODUCTION: Valvular disease and pulmonary hypertension are common conditions in haemodialysis patients. In presence of tricuspid regurgitation, an increased retrograde blood flow into the right atrium during ventricle systole results in a typical modification of the normal venous waveform, creating a giant c-v wave. This condition clinically appears as a venous palpable pulsation within the internal jugular vein, also known as Lancisi's sign. CASE REPORT: An 83-year-old woman underwent haemodialysis for 9 years. After arteriovenous fistula thrombosis, a right internal jugular vein non-tunnelled central venous catheter (CVC) was placed. About one month later, the patient was referred to our facility for the placement of a tunnelled CVC. Neck examination revealed an elevated jugular venous pulse, the Lancisi's sign. Surprisingly, chest x-ray posteroanterior view showed the non-tunnelled catheter tip in correspondence with the right ventricle. She underwent surgery for temporary to tunnelled CVC conversion using the same venous insertion site (Bellcath®10Fr-length 25 cm to Mahurkar®13.5Fr-length 19 cm). In the postoperative period, we observed a significant reduction of the jugular venous pulse. DISCUSSION: The inappropriate placement of a 25-cm temporary CVC in the right internal jugular vein worsened the tricuspid valve regurgitation, which became evident by the Lancisi's sign. Removal of the temporary CVC from the right ventricle resulted in improved right cardiac function. Safe approaches recommended by guidelines for the CVC insertion technique and for checking the tip position should be applied in order to avoid complications.

Doppler ultrasound venous mapping of the lower limbs.

BACKGROUND: The study aim was to test the accuracy (intra and interobserver variability), sensitivity, and specificity of a simplified noninvasive ultrasound methodology for mapping superficial and deep veins of the lower limbs. METHODS: 62 consecutive patients, aged 62 ± 11 years, were enrolled. All underwent US-examinations, performed by two different investigators, of both legs, four anatomical parts, and 17 veins, to assess the interobserver variability of evaluation of superficial and deep veins of the lower limbs. RESULTS: Overall the agreement between the second versus the first operator was very high in detecting reflux (sensitivity 97.9, specificity 99.7, accuracy 99.5; P = 0.80 at McNemar test). The higher CEAP classification stages were significantly associated with reflux (odds ratio: 1.778, 95% confidence interval: 1.552-2.038; P < 0.001) as well as with thrombosis (odds ratio: 2.765, 95% confidence interval: 1.741-4.389; P < 0.001). Thus, our findings show a strict association between the symptoms of venous disorders and ultrasound evaluation results for thrombosis or reflux. CONCLUSION: This study demonstrated that our venous mapping protocol is a reliable method showing a very low interobserver variability, which makes it accurate and reproducible for the assessment of the morphofunctional status of the lower limb veins.