Targeting early stages of cardiotoxicity from anti-PD1 immune checkpoint inhibitor therapy.

AIMS: Cardiac immune-related adverse events (irAEs) from immune checkpoint inhibition (ICI) targeting programmed death 1 (PD1) are of growing concern. Once cardiac irAEs become clinically manifest, fatality rates are high. Cardio-oncology aims to prevent detrimental effects before manifestation of severe complications by targeting early pathological changes. We therefore aimed to investigate early consequences of PD1 inhibition for cardiac integrity to prevent the development of overt cardiac disease. METHODS AND RESULTS: We investigated cardiac-specific consequences from anti-PD1 therapy in a combined biochemical and in vivo phenotyping approach. Mouse hearts showed broad expression of the ligand PDL1 on cardiac endothelial cells as a main mediator of immune-crosstalk. Using a novel melanoma mouse model, we assessed that anti-PD1 therapy promoted myocardial infiltration with CD4+ and CD8+ T cells, the latter being markedly activated. Left ventricular (LV) function was impaired during pharmacological stress, as shown by pressure-volume catheterization. This was associated with a dysregulated myocardial metabolism, including the proteome and the lipidome. Analogous to the experimental approach, in patients with metastatic melanoma (n = 7) receiving anti-PD1 therapy, LV function in response to stress was impaired under therapy. Finally, we identified that blockade of tumour necrosis factor alpha (TNFα) preserved LV function without attenuating the anti-cancer efficacy of anti-PD1 therapy. CONCLUSIONS: Anti-PD1 therapy induces a disruption of cardiac immune homeostasis leading to early impairment of myocardial functional integrity, with potential prognostic effects on the growing number of treated patients. Blockade of TNFα may serve as an approach to prevent the manifestation of ICI-related cardiotoxicity.

ECG Scoring for the Evaluation of Therapy-Naïve Cancer Patients to Predict Cardiotoxicity.

OBJECTIVE: To evaluate a new electrocardiographic (ECG) score reflecting domains of electrical and structural alterations in therapy-naïve cancer patients to assess their risk of cardiotoxicity. METHODS: We performed a retrospective analysis of 134 therapy-naïve consecutive cancer patients in our two university hospitals concerning four ECG score parameters: Contiguous Q-waves, markers of left ventricular (LV) hypertrophy, QRS duration and JTc prolongation. Cardiotoxicity was assessed after a short-term follow-up (up to 12 months). RESULTS: Of all the patients (n = 25), 19% reached 0 points, 50% (n = 67) reached 1 point, 25% (n = 33) reached 2 points, 5% (n = 7) reached 3 points and 0.7% reached 4 or 5 points (n = 1 respectively). The incidence of cardiotoxicity (n = 28 [21%]) increased with the ECG score, with 0 points at 0%, 1 point 7.5%, 2 points 55%, 3 points 71% and ≥3 points 50%. In the ROC (Receiver operating curves) analysis, the best cut-off for predicting cardiotoxicity was an ECG score of ≥2 points (sensitivity 82%, specificity 82%, AUC 0.84, 95% CI 0.77-0.92, p < 0.0001) which was then defined as a high-risk score. High-risk patients did not differ concerning their age, LV ejection fraction, classical cardiovascular risk factors or cardiac biomarkers compared to those with a low-risk ECG score. CONCLUSION: ECG scoring prior to the start of anti-cancer therapies may help to identify therapy-naïve cancer patients at a higher risk for the development of cardiotoxicity.

ECG Changes in Melanoma Patients Undergoing Cancer Therapy-Data From the ECoR Registry.

We aimed to evaluate whether therapy with immune checkpoint inhibitors (ICI) leads to changes in electrocardiogram (ECG) parameters in melanoma patients. We retrospectively examined 41 patients (46% women, age 61 ± 12years) with advanced melanoma (stage III/IV) before and during ICI treatment from our "Essen Cardio-oncology Registry" (ECoR). ECGs were analyzed before and 4-12 weeks after therapy started (follow-up, 90 ± 51 days). Heart rate, PR time, QRS duration and duration of the corrected QT (QTc) interval were recorded. QT dispersion (QTd) was calculated. Heart rate, PR time, QRS and QTc did not differ when comparing values before and after therapy started. QTd was prolonged after therapy started (32 ± 16 ms vs. 47 ± 19 ms, n = 41, p < 0.0001). Subgroup analyses revealed prolonged QTd in patients that received a combination immunotherapy with ipilimumab and nivolumab (31 ± 14 ms vs. 50 ± 14 ms, n = 21, p < 0.0001), while QTd in patients with anti-programmed death 1 (PD-1) inhibitor monotherapy did not change after therapy started. QTd is prolonged in patients under ICI combination therapy, potentially signaling an increased susceptibility to ventricular arrhythmias.

Troponins and Natriuretic Peptides in Cardio-Oncology Patients-Data From the ECoR Registry.

BACKGROUND: The long-term survival of cancer patients has significantly improved over the past years. Despite their therapeutic efficacy, various cancer therapies are associated with cardiotoxicity. Therefore, timely detection of cardiotoxic adverse events is crucial. However, the clinical assessment of myocardial damage caused by cancer therapy remains difficult. METHODS: This retrospective study was performed to evaluate the diagnostic value of cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for monitoring cancer therapy-induced cardiomyopathy. A total of 485 cancer patients referred to our cardio-oncology unit between July 2018 and January 2020 were selected from our Essen Cardio-oncology Registry (ECoR). We included patients with all types of cancer. Plasma concentrations of cTnI and NT-proBNP were measured by radioimmunoassay, and two-dimensional left ventricular ejection fraction (2D-LVEF), diastolic function, and global longitudinal strain (GLS) were measured by transthoracic echocardiography. In 116 patients, assessment was conducted before the induction of cancer therapy and during a short-term follow-up period; n = 42 of these were treated for malignant melanoma, and n = 42 with serial measurements were under treatment for breast cancer. RESULTS: In cross-sectional data, elevated NT-proBNP was associated with reduced LVEF and pathological GLS in the total cohort. A total of 116 patients had serial LVEF and biomarker measurements, and changes in NT-proBNP and troponin correlated with changes in LVEF during follow-up investigations. Similar to the total cohort, a subgroup of patients treated for malignant melanoma showed a correlation between the change in cTnI and the change in LVEF. In a subgroup analysis of patients undergoing breast cancer therapy, a correlation between the change in NT-proBNP and the change in LVEF could be detected. Thirty patients presented with chemotherapy-induced cardiomyopathy, defined as a significant LVEF decrease (> 10%) to a value below 50%. The number of patients with increased cTnI and NT-proBNP was significantly higher in patients with chemotherapy-induced cardiomyopathy than in patients without cardiotoxicity. Patients with positive cTnI and NT-proBNP were more likely to have a history of coronary heart disease, atrial fibrillation, and arterial hypertension. CONCLUSION: Our data suggest that cardiac biomarkers play an important role in the detection of cancer therapy-induced cardiotoxicity. Larger systematic assessment in prospective cohorts is mandatory.

Global longitudinal strain is associated with better outcomes in transcatheter aortic valve replacement.

BACKGROUND: Parameters that mark the timing of left ventricular (LV) reverse remodeling following transcatheter aortic valve replacement (TAVR) are incompletely defined. This study aims to identify the dynamics of LV strain derived from speckle tracking echocardiography in a cohort of patients with severe aortic stenosis (AS) who underwent TAVR and its correlation with postprocedural outcomes. METHODS: We selected 150 consecutive patients (82 ± 4 years old, STS score 6.4 ± 6.2) who underwent transfemoral TAVR between 07/2016 and 12/2017 at our tertiary care center. All patients were evaluated at baseline, 1 week after TAVR, and 3 months following TAVR. RESULTS: The global longitudinal strain (GLS) 1 week following TAVR was comparable to that at baseline (- 15,9 ± 4.3 vs - 16.8 ± 4.1; p = NS) but significantly improved at 3 months following TAVR (- 15.9 ± 4.3% vs. -19.5 ± 3.5%; p < 0.001). No significant changes in global circumferential strain (GCS) and global radial strain (GRS) were detectable. The ejection fraction was significantly improved 1 week after the TAVR procedure. The baseline GLS correlated directly with the complication rate (R = 0.36, p = 0.005). The linear regression analysis showed that the main predictors of the improvement in the GLS at 3 months in our cohort were baseline GRS and GCS. CONCLUSION: GLS improves at 3 months after TAVR, while LV ejection fraction does not show a substantial change, signaling an early recovery of LV longitudinal function after the intervention. Additionally, GLS has a direct correlation with the postprocedural outcomes. GLS improvement might emerge as a valuable parameter for a tailored follow-up in TAVR patients.

Impact of Bioprosthetic Choice on Mortality After Transfemoral Transcatheter Aortic Valve Implantation in Patients With Reduced Versus Preserved Left-Ventricular Ejection Fraction.

The outcome of transfemoral transcatheter aortic valve implantation (TF-TAVI) with a self-expanding (SEP) versus a balloon-expandable prosthesis (BEP) in patients with a reduced ejection fraction (rEF, ≤40%) has not been previously investigated. Patients with rEF have an increased risk of death after TF-TAVI compared to patients with a preserved ejection fraction (pEF), and prosthesis choice might influence the outcome of these patients. We, therefore, sought to compare all-cause mortality of patients with rEF using a SEP versus a BEP. We retrospectively analyzed data of 679 single-center TF-TAVI patients. Patients were censored at death or completion of 1-year follow-up, whichever occurred first. Patients with rEF (n = 141, 21%) had an increased 1-year mortality compared to patients with pEF (28% vs 19%, p = 0.007). SEP were implanted in 149 patients (49 with rEF, 33%), while BEP were implanted in 530 patients (92 with rEF, 17%). In patients with pEF, 1-year mortality was similar after SEP- and BEP-implantation (16% vs 19%, p = 0.516). In patients with rEF, however, 1-year mortality was higher after SEP- than after BEP-implantation (43% vs 21%, p = 0.004). These patients had a higher incidence of new permanent pacemaker implantation (26.5% vs 13%, p = 0.046) and paravalvular leak ≥II° (21% vs 10%, p = 0.07), but both factors could not explain the excess mortality after SEP-implantation in the multivariate analysis. In patients with rEF, the use of a SEP was an independent predictor of 1-year mortality (HR 2.44, 95% CI 1.27 to 4.27, p = 0.007). In conclusion, patients with rEF had a higher 1-year mortality after TF-TAVI when a SEP instead of a BEP was used.

Prolonged mechanical ventilation after left ventricular assist device implantation: risk factors and clinical implications.

AIMS: Unsuccessful weaning from ventilator after major cardiovascular procedures has been shown to be associated with increased post-operative morbidity and mortality. Our study aimed to identify predictors and clinical implications of prolonged mechanical ventilation (PMV) after left ventricular assist device (LVAD) implantation. METHODS AND RESULTS: We analysed the data of patients receiving a continuous-flow LVAD in our centre from December 2010 to September 2017. PMV was defined by a duration of invasive ventilation of >7 days after LVAD implantation. Multivariable logistic regression analysis was performed for predictors of PMV. Survival was estimated by the Kaplan-Meier method. During the study period, 156 patients received a continuous-flow LVAD in our centre. Seventeen patients were excluded due to early death (<7 days), and 139 patients were enrolled in the study (mean age: 58 years; male: 84%). The median duration of mechanical ventilation post-operatively was 94 h (range: 5 to 4192 h). PMV was observed in 43% of patients. Patients on PMV were characterized by a more severe disease state at baseline, compared with the group of early extubation, as reflected by their Interagency Registry for Mechanically Assisted Circulatory Support level (Level 1-3: 72 vs. 49%, P = 0.008). Patients on PMV exhibited higher pulmonary wedge pressures (25 vs. 21 mmHg, P = 0.04), lower estimated glomerular filtration rate (53 vs. 60 mL/min/1.73 m2 , P = 0.02), lower haemoglobin (10.6 vs. 11.6 g/dL, P = 0.02), and lower platelet counts (189 vs. 240/nL, P = 0.02). Previous sternotomy was more frequent in the PMV group (32 vs. 13%, P = 0.006). Higher rates of preoperative circulatory support (30 vs. 11.4%, P = 0.006), dialysis (31.7 vs. 10.1%, P = 0.001), and invasive ventilation (35 vs. 7.6%, P < 0.001) were reported for the PMV group. Logistic regression analysis revealed that estimated glomerular filtration rate [odds ratio (OR) 0.977, confidence interval (CI) 0.955-0.999, P = 0.038], platelet count (OR 0.994, CI 0.989-0.998, P = 0.008), and previous sternotomy (OR 5.079, CI 1.672-15.427, P = 0.004) were independent predictors of PMV. PMV was accompanied by longer intensive care unit (24 vs. 4 days, P < 0.001) and hospital stay (47 vs. 32 days, P = 0.003). Survival analysis revealed a profound increase in mortality at 180-day post-implantation in the PMV group (62 vs. 10%, log-rank: P < 0.001). CONCLUSIONS: Prolonged mechanical ventilation affects nearly half of patients after LVAD implantation. Previous sternotomy, renal function, and platelet counts are associated with increased risk for PMV. PMV is accompanied by decreased survival at 180-day post-implantation and longer hospitalizations.

Novel anticoagulants versus vitamin K antagonists for cardioversion of non- valvular atrial fibrillation - a meta-analysis of more than 17000 patients.

Non-vitamin K antagonist oral anticoagulants (NOACs) have proven a favorable risk-benefit profile compared to vitamin K antagonists (VKAs) for preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF), but actual data are not sufficiently powered to extend this profile on patients with AF that undergo cardioversion. We aimed to compare outcomes after cardioversion of AF under NOACs vs. VKAs. We systematically searched Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies published until October 2017. A total of 17506 patients from 11 studies were included. Treatment with NOACs was associated with similar relative risks (RR) of stroke and systemic embolism, hemorrhagic stroke, myocardial infarction, cardiovascular death, and all cause death compared to VKAs treatment. The RR of ischemic stroke was lower in the NOACs group. The risk of major bleeding was similar across treatment groups. Treatment with NOACs in patients with non-valvular AF that undergo cardioversion seems to be as safe and effective as the use of classical VKAs, with a better profile for ischemic stroke. Clinical Trial Registration: PROSPERO Registry, CRD42018086181 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID = 86181 .

Impact of baseline left ventricular ejection fraction on outcome after transfemoral transcatheter aortic valve implantation in patients with and without low-gradient aortic stenosis.

OBJECTIVES: To evaluate the impact of baseline left ventricular ejection fraction (LVEF) and its interaction with low-gradient aortic stenosis (LGAS) on all-cause mortality after transfemoral aortic valve implantation (TF-TAVI). METHODS: We reviewed mortality data of 624 consecutive single center TF-TAVI patients and categorized LVEF according to current ASE/EACVI recommendations (normal, mildly-, moderately-, and severely abnormal). RESULTS: Baseline LVEF was normal in 336 (53.8%), mildly abnormal in 160 (25.6%), moderately abnormal in 91 (14.6%), and severely abnormal in 37 (5.9%) patients, and 1-year mortality was 19%, 17%, 23%, and 43% (P = 0.002), respectively. Patients with LGAS had a similar 1-year mortality compared to those without LGAS in groups with normal (19% vs 19%, P = 0.899) and mildly abnormal LVEF (16% vs 17%, P = 0.898). One-year mortality of patients with LGAS was significantly greater than in those without LGAS in presence of moderately abnormal LVEF (31% vs 11%, P = 0.022), and it was numerically greater than in those without LGAS in presence of severely abnormal LVEF (48% vs 25%, P = 0.219). In multivariate analysis, only the combination of moderately/severely abnormal LVEF and LGAS predicted increased 1-year mortality (HR: 2.12, 95% CI: 1.4-3.2, P < 0.001). Other variables, including EuroSCORE I did not affect this result. CONCLUSIONS: Moderately/severely abnormal LVEF (≤40%) at baseline is associated with increased mortality after TF-TAVI, especially when the mean transvalvular aortic gradient is <40 mm Hg (LGAS), while outcomes in patients with normal and mildly abnormal LVEF are comparable regardless of the pressure gradient across the native aortic valve. (DRKS00013729).

Impaired Cardiac Function in Patients with Multiple Sclerosis by Comparison with Normal Subjects.

Multiple sclerosis (MS), neurologic disease affecting young population, may cause cardiovascular dysfunction, due to autonomous nervous dysfunction, physical invalidity, increased oxidative stress, and systemic inflammatory status. However, cardiovascular function is rarely evaluated in these patients. We assessed left and right ventricular (LV and RV) function by 2D, 3D, tissue Doppler, and speckle tracking echocardiography, and vascular function by remodeling, stiffness, and endothelial dysfunction parameters in patients with MS, compared to control subjects. 103 subjects (35 ± 10 years,70 women) were studied: 67 patients with MS and 36 control subjects. Patients with MS had decreased LV systolic function, confirmed by lower 2D and 3D ejection fraction, mitral annular plane systolic excursion, longitudinal myocardial systolic velocities, and 2D and 3D global longitudinal strain. The RV function was also decreased, as demonstrated by lower fractional area change, tricuspid annular plane systolic excursion, longitudinal systolic velocities, and longitudinal strain. Additionally, LV diastolic and left atrial (LA)  function were decreased compared to controls. The parameters of arterial and endothelial function were similar between groups. Patients with MS have impaired biventricular function by comparison with normal subjects, with reduced LA function, but normal arterial and endothelial function. The noninvasive echocardiographic techniques might help to determine patients with MS at risk of developing cardiovascular dysfunction.

Cardiovascular diseases in patients receiving small molecules with anti-vascular endothelial growth factor activity: A meta-analysis of approximately 29,000 cancer patients.

Background Targeted therapy with tyrosine kinase inhibitors with anti-vascular endothelial growth factor activity improves survival of cancer patients. Cardiovascular complications are critical and it is unknown whether these require specific treatment strategies. We aimed to clarify the associated risk of cardiovascular adverse events in patients treated with tyrosine kinase inhibitors. Design The design of this study was a meta-analysis of randomised controlled trials. Methods We searched PubMed, Cochrane, EMBASE and Web of Science databases for randomised controlled trials published until January 2017 that assessed patients with different types of cancer treated with or without tyrosine kinase inhibitors in addition to standard chemotherapy. Results A total of 29,252 patients from 71 randomised controlled trials were included. Tyrosine kinase inhibitor treatment was associated with a higher cardiac ischaemia relative risk (relative risk = 1.69; 95% confidence interval: 1.12-2.57; p = 0.01), with the highest risks observed for sorafenib and patients with renal cancer. Risk of thrombocytopaenia (relative risk = 2.2; 95% confidence interval: 1.73-2.79; p < 0.001) was highest for regorafenib and patients with breast cancer. Left ventricular systolic dysfunction was increased after tyrosine kinase inhibitor therapy (relative risk = 2.53; 95% confidence interval:1.79 - 3.57; p < 0.001), with the highest risks reported for sunitinib and hepatocellular cancer. QT corrected interval prolongation (relative risk = 6.25; 95% confidence interval: 3.44-11.38; p < 0.001) and arterial hypertension (relative risk = 3.78; 95% confidence interval: 3.15-4.54; p < 0.001) were reported. The relative risks of arterial adverse events, cerebral ischaemia, venous adverse events and pulmonary embolism were similar across groups. Conclusion Tyrosine kinase inhibitors increase the risk of severe cardiovascular and particularly thrombotic adverse events. Specific treatment regimens when prescribing tyrosine kinase inhibitor therapies appear desirable.

Cardiovascular Adverse Events in Patients With Cancer Treated With Bevacizumab: A Meta-Analysis of More Than 20 000 Patients.

BACKGROUND: The monoclonal antibody bevacizumab effectively inhibits angiogenesis in several types of cancers by blocking vascular endothelial growth factor. However, life-threatening cardiovascular adverse effects could limit its use and may warrant specific follow-up strategies. METHODS AND RESULTS: We systematically searched MEDLINE, Cochrane, EMBASE, and Web of Science for randomized controlled trials published until November 2016 that assessed patients with cancer treated with or without bevacizumab in addition to standard chemotherapy. A total of 20 050 patients with a broad range of cancer types from 22 studies were included in this analysis (10 394 in the bevacizumab group and 9656 in the control group). The risks of arterial and venous adverse events were higher in the bevacizumab groups (relative risk [RR], 1.37; 95% CI, 1.10-1.70 [P=0.004] and RR, 1.29; 95% CI, 1.12-1.47 [P<0.001], respectively), and more arterial adverse events occurred in patients taking high-dose bevacizumab regimens. Bevacizumab treatment was associated with the highest risk of cardiac and cerebral ischemia in the high-dose bevacizumab groups (RR, 4.4; 95% CI, 1.59-12.70 [P=0.004] and RR, 6.67; 95% CI, 2.17-20.66 [P=0.001], respectively). In addition, the risk of bleeding and arterial hypertension were higher in the bevacizumab groups (RR, 2.74; 95% CI, 2.38-3.15 [P<0.001] and RR, 4.73; 95% CI, 4.15-5.39 [P<0.00001], respectively), with higher values for patiens taking high-dose regimens. CONCLUSIONS: Treatment with bevacizumab increases the risk of arterial adverse events, particularly cardiac and cerebral ischemia, venous adverse events, bleeding, and arterial hypertension. This risk is additionally increased with high doses of bevacizumab. Further studies should determine the appropriate options for cardio-oncology management. CLINICAL TRIAL REGISTRATION: URL: https://www.crd.york.ac.uk. Unique identifier: PROSPERO(CRD42016054305).

Preprocedural C-Reactive Protein Predicts Outcomes after Primary Percutaneous Coronary Intervention in Patients with ST-elevation Myocardial Infarction a systematic meta-analysis.

Risk assessment in patients with acute coronary syndromes (ACS) is critical in order to provide adequate treatment. We performed a systematic meta-analysis to assess the predictive role of serum C-reactive protein (CRP) in patients with ST-segment elevation myocardial infarction (STEMI), treated with primary percutaneous coronary intervention (PPCI). We included 7 studies, out of 1,033 studies, with a total of 6,993 patients with STEMI undergoing PPCI, which were divided in the high or low CRP group, according to the validated cut-off values provided by the corresponding CRP assay. High CRP values were associated with increased in-hospital and follow-up all-cause mortality, in-hospital and follow-up major adverse cardiac events (MACE), and recurrent myocardial infarction (MI). The pre-procedural CRP predicted in-hospital target vessel revascularization (TVR), but was not associated with acute/subacute and follow-up in-stent restenosis (ISR), and follow-up TVR. Thus, pre-procedural serum CRP could be a valuable predictor of global cardiovascular risk, rather than a predictor of stent-related complications in patients with STEMI undergoing PPCI. This biomarker might have the potential to improve the management of these high-risk patients.

Cardiovascular Dysfunction in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic neurological condition, characterized by recurrent episodes of inflammation and demyelination of the central nervous system called relapsing-remitting episodes, and continuous axonal degeneration that leads to irreversible progressive invalidity. Patients with multiple sclerosis present a higher mortality rate compared to the general population, and the excess of mortality may be explained by the increased cardiovascular risk and occurrence of cardiovascular disease. However, the exact pathways to cardiovascular dysfunction are not yet completely elucidated. This review focuses on the most important mechanisms of cardiovascular dysfunction in MS, such as the cardiomyocite structure alteration, the cardiovascular autonomous nervous system dysfunction, physical invalidity, oxidative stress and endothelial dysfunction, as well as the impact of cardiovascular risk factors in MS. The latest evidence about therapeutic approaches for MS, such as immunomodulatory treatment, vitamin D supplementation and statins are also discussed. There is little knowledge about the cardiovascular dysfunction in MS, and further research is required to improve the understanding of these complex mechanisms.

New Echocardiographic Tehniques in Pulmonary Arterial Hypertension vs. Right Heart Catheterization - A Pilot Study.

BACKGROUND: Pulmonary arterial hypertension (PAH) represents an emerging pathology in modern medicine. Transthoracic echocardiography is an inexpensive and reproducible method and it is the most commonly used non-invasive diagnostic tool to asses pulmonary artery pressure (PAP) and the function of the right ventricle. Although, the right heart catheterization is still considered as the standard for the diagnosis, according to the last guidelines, the new echocardiographic methods may offer an improved value in the PAH evaluation. AIM: To evaluate if cardiac ultrasonography data correlate with catheterization results in patients with PAH (Group I Dana Point 2008), and to compare the ultrasonography evaluation of PAH patients with that of normal. METHODS: 15 consecutive patients (pts) (52±15 yrs, 5 men, time from onset of symptoms 1.6±1.7 years) with PAH of different aetiologies (12 pts with idiopathic PAH, 2 pts with PAH associated with scleroderma and one with persistent PAH after atrial septal defect (ASD) closure) were evaluated through: 1. clinical examination (NYHA class); 2. exercise capacity (6 minute walking test - 6MWT); 3. conventional echocardiography (diameter of right ventricle - RVD and right atrium, fractional area shortening - FAS, TAPSE, pulmonary ascension time - PA, systolic and mean PAP -sPAP, mPAP, tricuspid E/A ratio, cardiac index-CI) and 4. Tissue Doppler Imaging - TDI (systolic and diastolic myocardial velocities at the tricuspid annulus - S, D, A); 5. right heart catheterization (sPAP, mPAP, CI, pulmonary vascular resistance - PVR)We compared classical and TDI echo parameters with those obtained from 15 normal subjects, matched in age and sex. RESULTS: PAH patients had high sPAP and mPAP with right heart dilation (RV - 44.8±7.3 mm), depressed TAPSE (16.2±5.9 mm) and cardiac index and low TDI systolic velocities at tricuspid level (7.3±2.9 cm/s). All parameters differed statistically significant from normal. There were no significant correlations between ultrasonography and catheterization (cath) parameters (sPAP 92±28.2 echo vs. 106.4±25.8 mmHg cath; mPAP 47.9±8.4 echo vs. 65.8±17.3 mmHg cath), excepting for CI 2.3±1.2 l/min/m(2) vs. 2.08±0.3 ml/min/m(2)) and PVR (16.5 ± 15.3 Wood U echo, vs. 19.6 ± 7.9 cath). CONCLUSION: Classic and TDI cardiac ultrasonography represents a good screening and monitoring tool for PAH patients, but tends to underestimate the severity of the disease, leaving right heart catheterization as the essential diagnostic method for this rare disease.