Incidence of Bloodstream Infection in Patients with Pulmonary Hypertension under Intravenous Epoprostenol or Iloprost-A Multicentre, Retrospective Study.

Intravenous synthetic prostacyclin analogs (iPCAs), such as epoprostenol, treprostinil and iloprost have been widely used for the treatment of pulmonary arterial hypertension (PAH). Despite having good outcomes, continuous infusion of iPCAs has been associated with some adverse effects. Bloodstream infection (BSI) is one of the most severe complications, although poorly recognized, especially under iloprost administration, which few studies have addressed. This study aimed to compare the BSI incidence rates between intravenous iloprost and epoprostenol administration. Patients with pulmonary hypertension (PH) functional class III or IV receiving intravenous iloprost or epoprostenol through Hickman catheter, between 2004 and 2019, were retrospectively selected from two PH treatment centers. From a total of 36 patients (13 for iloprost and 23 for epoprostenol), 75% (n = 27) fulfilled the PAH criteria, mainly belonging to the idiopathic group. Overall BSI rate was 1.5/1000 days of treatment (3.38 and 0.09/1000 days for iloprost and epoprostenol, respectively). Patients receiving iloprost were at a higher risk of developing BSI than those receiving epoprostenol (HR: 12.5; 95% CI: 1.569-99.092). A higher mortality rate from BSI was also identified in the iloprost group (p = 0.04). Twenty-seven patients developed BSI, with 92% of them requiring hospitalization. A total of 29 agents were found, 10 Gram-positive (mainly Staphylococcus aureus; n = 5) and 19 Gram-negative (mainly Pseudomonas aeruginosa; n = 6) bacteria. Iloprost administration was linked to a significantly higher incidence of BSI, worse prognosis, and more BSI-related deaths than epoprostenol. BSI due to Gram-negative, commensal, low-virulence bacteria was also higher in the iloprost group. In short, physicians should be aware when prescribing iPCA to guarantee their patients' safety and best medical care.

Chronic thromboembolic pulmonary hypertension: A 10-year analysis from a Portuguese referral center.

INTRODUCTION AND OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive, but potentially curable, form of pulmonary hypertension. Pulmonary endarterectomy (PEA) is a complex surgery that frequently achieves hemodynamic normalization and symptom resolution, although not all patients are suitable for the procedure. We aimed to assess long-term outcomes of CTEPH, namely all-cause mortality and hospital admission for decompensated heart failure, according to treatment modalities in patients who underwent PEA or non-surgical therapy. METHODS: A 10-year retrospective study of patients with CTEPH at a referral center was conducted. Forty-five patients were included and median follow-up time was 57 (IQR 24-93) months. Survival analysis was performed and a multivariate Cox regression model was used to identify independent predictors of outcomes. RESULTS: Patients were mostly female (59%) and mean age was 63±16 years. Two-thirds were severely symptomatic at diagnosis, with 62.2% of patients presenting in WHO functional class (WHO FC) III or IV. One-, two- and three-year survival was 93.3%, 82.4% and 75.9%, respectively. Serum BNP (HR 1.003; 95% CI: 1.001-1.005; p=0.003) and creatinine (HR 12.092; 95% CI: 1.121-130.390; p=0.040) were predictors of death. Mortality was numerically lower in those who underwent PEA (p=0.135). PEA was associated with decreased risk of the combined endpoint of all-cause mortality and hospital admission for decompensated heart failure (HR 0.198; 95% CI: 0.040-0.982; p=0.047), as were lower serum BNP (HR 1.003; 95% CI: 1.001-1.005; p=0.008) and mPAP (HR 1.073; 95% CI: 1.022-1.128; p=0.005) at diagnosis. Most patients who underwent PEA presented improved WHO FC (92.9%) and post-surgical residual pulmonary hypertension was identified in only 21.4%. CONCLUSION: PEA provided a better overall prognosis than non-surgical therapy, improving symptoms and frequently achieving hemodynamic normalization, with a numerical trend for lower mortality. Higher serum BNP, creatinine and mPAP at diagnosis were independently associated with worse outcomes.

Atrial Mechanics in Hypertrophic Cardiomyopathy: Discriminating between Ventricular Hypertrophy and Fibrosis. / Mecânica Atrial na Cardiomiopatia Hipertrófica: Discriminando Hipertrofia de Fibrose Ventricular.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) secondary to systemic hypertension (HTN) may be associated with left atrial (LA) functional abnormalities. OBJECTIVES: We aimed to characterize LA mechanics in HCM and HTN and determine any correlation with the extent of left ventricular (LV) fibrosis measured by cardiac magnetic resonance (CMR) in HCM patients. METHODS: Two-dimensional speckle tracking-derived longitudinal LA function was acquired from apical views in 60 HCM patients, 60 HTN patients, and 34 age-matched controls. HCM patients also underwent CMR, with measurement of late gadolinium enhancement (LGE) extension. Association with LA strain parameters was analyzed. Statistical significance was set at p<0.05. RESULTS: Mean LV ejection fraction was not different between the groups. The E/e' ratio was impaired in the HCM group and preserved in the control group. LA mechanics was significantly reduced in HCM, compared to the HTN group. LA strain rate in reservoir (LASRr) and in contractile (LASRct) phases were the best discriminators of HCM, with an area under the curve (AUC) of 0.8, followed by LA strain in reservoir phase (LASr) (AUC 0.76). LASRr and LASR-ct had high specificity (89% and 91%, respectively) and LASr had sensitivity of 80%. A decrease in 2.79% of LA strain rate in conduit phase (LASRcd) predicted an increase of 1cm in LGE extension (r2=0.42, ß 2.79, p=0.027). CONCLUSIONS: LASRr and LASRct were the best discriminators for LVH secondary to HCM. LASRcd predicted the degree of LV fibrosis assessed by CMR. These findings suggest that LA mechanics is a potential predictor of disease severity in HCM.

FUNDAMENTO: A cardiomiopatia hipertrófica (CMH) e a hipertrofia ventricular esquerda (HVE) secundária à hipertensão arterial sistêmica (HAS) podem estar associadas a anormalidades funcionais do átrio esquerdo (AE). OBJETIVOS: Caracterizar a mecânica do AE na CMH e na HAS e avaliar qualquer correlação com a extensão da fibrose ventricular esquerda medida por ressonância magnética cardíaca (RMC) em pacientes com CMH. MÉTODOS: A função longitudinal do AE derivada do ecocardiograma bidimensional com speckle tracking foi adquirida a partir de cortes apicais de 60 pacientes com CMH e 34 indivíduos controles, pareados por idade. Pacientes com CMH também foram submetidos à RMC, com medida da extensão do realce tardio por gadolínio. A associação com parâmetros de strain do AE foi analisada. Valores p < 0,05 foram definidos como estatisticamente significativos. RESULTADOS: A média da fração de ejeção do ventrículo esquerdo não foi diferente entre os grupos. A razão E/e' estava comprometida no grupo CMH e preservada no grupo controle. A mecânica do AE estava significativamente reduzida na CMH em comparação aos pacientes com HAS. O strain rate do AE nas fases de reservatório (SRrAE) e na fase contrátil (SRctAE) foram os melhores parâmetros de discriminação de CMH com uma área sob a curva (AUC) de 0,8, seguido do strain do AE na fase de reservatório (SrAE) (AUC 0,76). O SRrAE e o SRctAE apresentaram elevada especificidade (89% e 91%, respectivamente), e o SrAE apresentou sensibilidade de 80%. Um decréscimo de 2,79% no strain rate do AE na fase de condução (SRcdAE) foi preditor de um aumento de 1 cm na extensão do RT pelo gadolínio (r2=0,42, ß 2,79, p=0,027). CONCLUSÕES: O SRrAE e o SRctAE foram os melhores fatores de discriminação de HVE secundária à CMH. O SRcdAE foi preditor do grau de fibrose ventricular esquerda avaliada por RMC. Esses achados sugerem que a mecânica do AE pode ser um potencial preditor de gravidade de doença na CMH.

Mecânica Atrial na Cardiomiopatia Hipertrófica: Discriminando Hipertrofia de Fibrose Ventricular / Atrial Mechanics in Hypertrophic Cardiomyopathy: Discriminating between Ventricular Hypertrophy and Fibrosis

Resumo Fundamento A cardiomiopatia hipertrófica (CMH) e a hipertrofia ventricular esquerda (HVE) secundária à hipertensão arterial sistêmica (HAS) podem estar associadas a anormalidades funcionais do átrio esquerdo (AE). Objetivos Caracterizar a mecânica do AE na CMH e na HAS e avaliar qualquer correlação com a extensão da fibrose ventricular esquerda medida por ressonância magnética cardíaca (RMC) em pacientes com CMH. Métodos A função longitudinal do AE derivada do ecocardiograma bidimensional com speckle tracking foi adquirida a partir de cortes apicais de 60 pacientes com CMH e 34 indivíduos controles, pareados por idade. Pacientes com CMH também foram submetidos à RMC, com medida da extensão do realce tardio por gadolínio. A associação com parâmetros de strain do AE foi analisada. Valores p < 0,05 foram definidos como estatisticamente significativos. Resultados A média da fração de ejeção do ventrículo esquerdo não foi diferente entre os grupos. A razão E/e' estava comprometida no grupo CMH e preservada no grupo controle. A mecânica do AE estava significativamente reduzida na CMH em comparação aos pacientes com HAS. O strain rate do AE nas fases de reservatório (SRrAE) e na fase contrátil (SRctAE) foram os melhores parâmetros de discriminação de CMH com uma área sob a curva (AUC) de 0,8, seguido do strain do AE na fase de reservatório (SrAE) (AUC 0,76). O SRrAE e o SRctAE apresentaram elevada especificidade (89% e 91%, respectivamente), e o SrAE apresentou sensibilidade de 80%. Um decréscimo de 2,79% no strain rate do AE na fase de condução (SRcdAE) foi preditor de um aumento de 1 cm na extensão do RT pelo gadolínio (r2=0,42, β 2,79, p=0,027). Conclusões O SRrAE e o SRctAE foram os melhores fatores de discriminação de HVE secundária à CMH. O SRcdAE foi preditor do grau de fibrose ventricular esquerda avaliada por RMC. Esses achados sugerem que a mecânica do AE pode ser um potencial preditor de gravidade de doença na CMH.

Abstract Background Hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) secondary to systemic hypertension (HTN) may be associated with left atrial (LA) functional abnormalities. Objectives We aimed to characterize LA mechanics in HCM and HTN and determine any correlation with the extent of left ventricular (LV) fibrosis measured by cardiac magnetic resonance (CMR) in HCM patients. Methods Two-dimensional speckle tracking-derived longitudinal LA function was acquired from apical views in 60 HCM patients, 60 HTN patients, and 34 age-matched controls. HCM patients also underwent CMR, with measurement of late gadolinium enhancement (LGE) extension. Association with LA strain parameters was analyzed. Statistical significance was set at p<0.05. Results Mean LV ejection fraction was not different between the groups. The E/e' ratio was impaired in the HCM group and preserved in the control group. LA mechanics was significantly reduced in HCM, compared to the HTN group. LA strain rate in reservoir (LASRr) and in contractile (LASRct) phases were the best discriminators of HCM, with an area under the curve (AUC) of 0.8, followed by LA strain in reservoir phase (LASr) (AUC 0.76). LASRr and LASR-ct had high specificity (89% and 91%, respectively) and LASr had sensitivity of 80%. A decrease in 2.79% of LA strain rate in conduit phase (LASRcd) predicted an increase of 1cm in LGE extension (r2=0.42, β 2.79, p=0.027). Conclusions LASRr and LASRct were the best discriminators for LVH secondary to HCM. LASRcd predicted the degree of LV fibrosis assessed by CMR. These findings suggest that LA mechanics is a potential predictor of disease severity in HCM.

Left atrial mechanics in moderate mitral valve disease: earlier markers of damage.

While the impairment of left atrial (LA) mechanics in mitral valve disease is well known, the exact onset of reservoir, conduit, and contractile dysfunction in mitral stenosis (MS) and mitral regurgitation (MR) remains unclear. We aimed to clarify the LA deformation mechanics in patients with moderate mitral valve disease. We conducted a prospective observational study of 80 patients with moderate isolated MR, 80 patients with moderate isolated MS, and 64 age-matched controls without mitral valve disease. Strain (ɛ) and strain rate (SR) on speckle tracking echocardiography were assessed as indicators of LA and right atrium (RA) reservoir (ɛsys, SRs), conduit (ɛe, SRe), and contractile (ɛa, SRa) functions. Conventional echocardiographic parameters of the left ventricle (LV) were also assessed. Comparisons were conducted according to mitral valve pathology (MR patients, MS patients, controls). The mean LV ejection fraction, end-diastolic diameter, and global longitudinal strain did not differ across the groups. The pulmonary artery systolic pressure, LA volume indexed to body surface area, and LA mechanics were significantly impaired in mitral valve disease (patients vs controls). While LA ɛ did not vary between MR and MS, MR patients had better LA SRs and SRe but worse SRa (p < 0.01). SRe > - 0.65% had higher specificity for MS, with an area under the curve of 0.85 (p < 0.01). RA mechanics were significantly impaired in mitral valve disease (patients vs controls) but did not vary significantly with disease pathology (MS vs MR). Patients with moderate mitral valve disease exhibit early and pathology-specific changes in the LA deformation mechanics, manifesting mainly as impaired contractile-phase SR in MR and impaired conduit-phase SR in MS. Our findings highlight SR as a potentially useful early marker of LA dysfunction in relation to mitral valve disease.

Going beyond classic echo in aortic stenosis: left atrial mechanics, a new marker of severity.

BACKGROUND: There is limited information regarding left atrial (LA) mechanics in aortic valve stenosis (AS). We assessed LA mechanics in AS through speckle-tracking echocardiography (STE) according to severity and prognosis. METHODS: We included 102 patients diagnosed with severe AS (sAS) and 80 patients with moderate AS (mAS), all with preserved ejection fraction and no coronary artery disease. LA mechanics and left ventricular global longitudinal strain (LV-GLS) were assessed by STE. The cohort was followed-up for a median of 30 (IQR 12.6-50) months, and outcomes were determined (combined outcome of HF, death, and aortic valve replacement). RESULTS: In our sample set, values of LV-GLS (- 18.5% vs - 17.1, p = 0.025), E/e' ratio (15.8 vs 18.4, p = 0.03), and global LA mechanics (LA ɛsys, 23% vs 13.8%, p < 0.001) were worse for sAS compared to those for mAS. However, LA ɛsys (AUC 0.85, 95% CI 0.78-0.90, p < 0.001), ɛe (AUC 0.83, 95% CI 0.75-0.88, p < 0.001), and ɛa (AUC 0.80, 95% CI 0.70-0.84, p < 0.001) were the best discriminators of sAS, with sensitivities higher than 85%. LA ɛsys showed a stronger correlation with both aortic valve area (r2 = 0.6, p < 0.001) and mean LV/aortic gradient (r2 = 0.55, p < 0.001) than LV-GLS (r2 = 0.3 and r2 = 0.25, p = 0.01). Either LV-GLS or LA ɛsys, but not the E/e' ratio, TAPSE, or RV/RA gradient, were a significant predictors of the combined outcome. CONCLUSIONS: LA global strain was the best discriminator of severity, surpassing E/e' ratio and LV-GLS, and a significant predictor of prognosis in AS.

MicroRNA-424(322) as a new marker of disease progression in pulmonary arterial hypertension and its role in right ventricular hypertrophy by targeting SMURF1.

Aims: MicroRNAs (miRNAs) have been implicated in the pathogenesis of pulmonary hypertension (PH), a multifactorial and progressive condition associated with an increased afterload of the right ventricle leading to heart failure and death. The main aim of this study was to correlate the levels of miR-424(322) with the severity and prognosis of PH and with right ventricle hypertrophy progression. Additionally, we intended to evaluate the mechanisms and signalling pathways whereby miR-424(322) secreted by pulmonary arterial endothelial cells (PAECs) impacts cardiomyocytes. Methods and results: Using quantitative real-time PCR, we showed that the levels of circulating miR-424(322) are higher in PH patients when compared with healthy subjects. Moreover, we found that miR-424(322) levels correlated with more severe symptoms and haemodynamics. In the subgroup of Eisenmenger syndrome patients, miR-424(322) displayed independent prognostic value. Furthermore, we demonstrated that miR-424(322) targets SMURF1, through which it sustains bone morphogenetic protein receptor 2 signalling. Moreover, we showed that hypoxia induces the secretion of miR-424(322) by PAECs, which after being taken up by cardiomyocytes leads to down-regulation of SMURF1. In the monocrotaline rat model of PH, we found an association between circulating miR-424(322) levels and the stage of right ventricle hypertrophy, as well as an inverse correlation between miR-424(322) and SMURF1 levels in the hypertrophied right ventricle. Conclusions: This study shows that miR-424(322) has diagnostic and prognostic value in PH patients, correlating with markers of disease severity. Additionally, miR-424(322) can target proteins with a direct effect on heart function, suggesting that this miRNA can act as a messenger linking pulmonary vascular disease and right ventricle hypertrophy.

Left atrial mechanics strongly predict functional capacity assessed by cardiopulmonary exercise testing in subjects without structural heart disease.

Left atrium function is essential for cardiovascular performance and is evaluable by two-dimensional speckle-tracking echocardiography (2D-STE). Our aim was to determine how echocardiographic parameters interrelate with exercise capacity and ventilatory efficiency in subjects with no structural heart disease. Asymptomatic volunteers, in sinus rhythm and with normal biventricular size and function, were recruited from a community-based population. Individuals with moderate-to-severe valvular disease, pulmonary hypertension, and history of cardiac disease were excluded. We performed a transthoracic echocardiogram and assessed left atrial (LA) and left ventricular (LV) mechanics via 2D-STE. Cardiopulmonary exercise testing by treadmill took place immediately thereafter. Peak oxygen uptake (VO2) served as measure of functional capacity and ventilation/carbon dioxide output (VE/VCO2) slope as surrogate of ventilation/perfusion mismatch. 20 subjects were included (age 51 ± 14 years, male gender 65%). Peak VO2 strongly correlated with age (r = -0.83; P < 0.01), with E/e' ratio (r = -0.72; P < 0.01), and with LA reservoir- and conduit-phase mechanics, particularly with LA conduit strain rate (SR) (r = -0.82; P < 0.01), but showed no correlation with LA volume index or LV mechanics. A similar pattern of associations was identified for VE/VCO2 slope. In multivariate analysis, LA conduit SR (ß = -0.69; P = 0.02) emerged as sole independent correlate of peak VO2, adjusted for age and for E/e' ratio (adjusted r 2 = 0.76; P < 0.01). Conduit and reservoir components of LA mechanics displayed strong associations with peak VO2 and VE/VCO2 slope. LA conduit-phase SR seems best suited as echocardiographic marker of functional capacity in subjects with no structural heart disease.

Exercise echocardiography for the assessment of pulmonary hypertension in systemic sclerosis: a systematic review.

BACKGROUND: Pulmonary arterial hypertension (PAH) complicates the course of systemic sclerosis (SSc) and is associated with poor prognosis. The elevation of systolic pulmonary arterial pressure (sPAP) during exercise in patients with SSc with normal resting haemodynamics may anticipate the development of PAH. Exercise echocardiography (ExEcho) has been proposed as a useful technique to identify exercise-induced increases in sPAP, but it is unclear how to clinically interpret these findings. In this systematic review, we summarize the available evidence on the role of exercise echocardiography to estimate exercise-induced elevations in pulmonary and left heart filling pressures in patients with systemic sclerosis. METHODS: We conducted a systematic review of the literature using MEDLINE, Cochrane Library and Web of Knowledge, using the vocabulary terms: ('systemic sclerosis' OR 'scleroderma') AND ('exercise echocardiography') AND ('pulmonary hypertension'). Studies including patients with SSc without a prior diagnosis of PAH, and subjected to exercise echocardiography were included. All searches were limited to English and were augmented by review of bibliographic references from the included studies. The quality of evidence was assessed by the Effective Public Health Practice Project system. RESULTS: We identified 15 studies enrolling 1242 patients, who were mostly middle-aged and female. Several exercise methods were used (cycloergometer, treadmill and Master's two step), with different protocols and positions (supine, semi-supine, upright); definition of a positive test also varied widely. Resting estimated sPAP levels varied from 18 to 35 mm Hg, all in the normal range. The weighted means for estimated sPAP were 22.2 ± 2.9 mmHg at rest and 43.0 ± 4.3 mmHg on exercise; more than half of the studies reported mean exercise sPAP ≥40 mmHg. The assessment of left ventricular diastolic function on peak exercise was reported in a minority of studies; however, when assessed, surrogate variables of left ventricular (LV) diastolic dysfunction were associated with higher sPAP on exercise. CONCLUSIONS: We found very high heterogeneity in the methods, the protocols and the estimated sPAP response to exercise. LV diastolic dysfunction was common and was associated with greater elevation of sPAP on exercise.

Aortic Valve Disease and Vascular Mechanics: Two-Dimensional Speckle Tracking Echocardiographic Analysis.

PURPOSE: Degenerative aortic valve disease (AVD) is a complex disorder that goes beyond valve itself, also undermining aortic wall. We aimed to assess the ascending aortic mechanics with two-dimensional speckle tracking echocardiography (2DSTE) in patients with aortic regurgitation (AR) and hypothesized a relationship with degree of AR. Aortic mechanics were then compared with those of similarly studied healthy controls and patients with aortic stenosis (AS); finally, we aimed to assess the prognostic significance of vascular mechanics in AVD. METHODS: Overall, 73 patients with moderate-to-severe AR and 22 healthy subjects were enrolled, alongside a previously examined cohort (N = 45) with moderate-to-severe AS. Global circumferential ascending aortic strain (CAAS) and strain rate (CAASR) served as indices of aortic deformation; corrected CAAS was calculated as CAAS/pulse pressure (PP). Median clinical follow-up was 438 days. RESULTS: In patients with severe (vs. moderate) AR, CAASR (1.53 ± 0.29/sec vs. 1.90 ± 0.62/sec, P < 0.05) and corrected CAAS (0.14 ± 0.06%/mmHg vs. 0.19 ± 0.08%/mmHg, P < 0.05) were significantly lower, whereas CAAS did not differ significantly. Measurers of aortic mechanics (CAAS, corrected CAAS, CAASR) differed significantly (all P < 0.01) in patients with AS and AR and in healthy subjects, with lower values seen in patients with AS. In follow-up, survival rate of AVD patients with baseline CAASR >0.88/sec was significantly higher (log rank, 97.4% vs. 73.0%; P = 0.03). CONCLUSIONS: Quantitative measures of aortic mechanics were lower for AS patients, suggesting a more significant derangement of aortic elastic properties. In the context of AVD, vascular mechanics assessment proved useful in gauging clinical prognosis.

Pulmonary hypertension in Portugal: first data from a nationwide registry.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare disease that must be managed in specialized centers; therefore, the availability of epidemiological national data is critical. METHODS: We conducted a prospective, observational, and multicenter registry with a joint collaboration from five centers from Portugal and included adult incident patients with PAH or chronic thromboembolic pulmonary hypertension (CTEPH). RESULTS: Of the 79 patients enrolled in this study, 46 (58.2%) were classified as PAH and 33 patients (41.8%) as CTEPH. PAH patients had a mean age of 43.4 ± 16.4 years. Idiopathic PAH was the most common etiology (37%). At presentation, PAH patients had elevated right atrial pressure (RAP) (7.7 ± 5.9 mmHg) and mean pulmonary vascular resistance (11.4 ± 6.5 Wood units), with a low cardiac index (2.7 ± 1.1 L·min(-1)·m(-2)); no patient was under selective pulmonary vasodilators; however, at follow-up, most patients were on single (50%), double (28%), or triple (9%) combination vasodilator therapy. One-year survival was 93.5%, similar to CTEPH patients (93.9%), that were older (60.0 ± 12.5 years) and had higher RAP (11.0 ± 5.2 mmHg, P = 0.015). CONCLUSIONS: We describe for the first time nationwide data on the diagnosis, management, and prognosis of PAH and CTEPH patients in Portugal. Clinical presentation and outcomes are comparable with those reported on other national registries.

Predictors of pulmonary hypertension after intermediate-to-high risk pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is a common cardiovascular emergency that, when combined with chronic thromboembolic pulmonary hypertension (PH), is associated with high mortality and morbidity. We aimed to determine the incidence of and predisposing factors for the development of PH after a PE episode. METHODS: A retrospective study was conducted in 213 patients admitted to an intensive care unit with intermediate-to-high risk PE between 2000 and 2010. Clinical data at admission were collected and the incidence of PH as assessed by echocardiography (estimated pulmonary systolic artery pressure over 40 mmHg) was determined. Multivariate analysis was used to determine predictors of development of PH. RESULTS: PH was detected in 12.4% of patients after a mean follow-up of three years. Only age (hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.02-1.20 per year; p=0.012) and body mass index (HR 1.19, 95% CI 1.04-1.36) per kg/m2, p=0.013) emerged as independent predictors of the development of this complication during follow-up. CONCLUSIONS: PH after PE was a relatively common complication in our series. We identified advanced age and increased body mass index as predisposing factors.

Long-term effect of bosentan in pulmonary hypertension associated with complex congenital heart disease.

BACKGROUND: Bosentan is recommended for symptomatic patients with Eisenmenger syndrome due to simple congenital lesions such as atrial and ventricular septal defects (VSD). However, its long-term efficacy and safety in patients with pulmonary arterial hypertension (PAH) associated with complex congenital heart disease (CHD) is unknown. OBJECTIVES: We examined the short- and long-term effects and safety profile of bosentan in patients with PAH and complex CHD. METHODS: We followed 14 patients with PAH and complex CHD for a mean of four years. Demographic parameters, exercise capacity assessed by the six-minute walking test (6MWT) and oxygen saturation were assessed at baseline, six months and at follow-up. RESULTS: Mean age was 37.1 ± 11.7 years; 90% were in WHO class III or IV. The most common diagnosis was pulmonary atresia with VSD (35.7%), followed by truncus arteriosus (28.6%), patent ductus arteriosus (21.4%) and transposition of the great arteries (14.3%). After six months of treatment, six-minute walking distance (6MWD) increased from 371.9 to 428.4 m (p=0.005) and functional class was improved (p=0.005). After four years, one patient discontinued bosentan due to side effects and four patients were started on sildenafil, after a mean 38 months of bosentan treatment. Mean 6MWD for patients on bosentan monotherapy (n=8) was 440.1 ± 103.8 m, whereas for patients on bosentan-sildenafil combination therapy (n=4) it was 428.8 ± 96.9 m, after four years of therapy. Two patients died during follow-up. CONCLUSIONS: Bosentan was safe and was associated with improved exercise capacity in patients with PAH and complex CHD. This improvement was sustained for up to four years and the safety profile was similar to simple CHD patients.

Circumferential ascending aortic strain and aortic stenosis.

BACKGROUND: Two-dimensional speckle tracking (2D-ST) echocardiography for the measurement of circumferential ascending thoracic aortic strain (CAAS) in the context of aortic stenosis (AS) is not elucidated. Purpose This study assesses the thoracic ascending aortic deformation using 2D-ST echocardiography in AS patients. Population and methods Forty-five consecutive patients with an aortic valvular area (AVA) ≤0.85 cm(2)/m(2) were included. Regarding aortic deformation, the global peak CAAS was the parameter used, and an average of six segments of arterial wall deformation was calculated. The corrected CAAS was calculated as the global CAAS/pulse pressure (PP). Aortic stiffness (ß2) index was assessed according to ln(Ps/Pd)/CAAS. The sample was stratified according to the stroke volume index (SVI) as: Group A (low flow, SVI ≤35 mL/m(2); n = 19) and Group B (normal flow, SVI >35 mL/m(2); n = 26). RESULTS: The mean age was 76.8 ± 10.3 years, 53.3% were male, the mean indexed AVA was 0.43 ± 0.15 cm(2)/m(2), and the mean CAAS was 6.3 ± 3.0%. The CAAS was predicted by SVI (ß = 0.31, P < 0.01) and by valvulo-arterial impedance (Zva). The corrected CAAS was correlated with the M-mode guided aortic stiffness index (ß1) (r = -0.39, P < 0.01), and was predicted by SVI, Zva, and systemic arterial compliance (ß = 0.15, P < 0.01). The ß2 index was significantly higher for the low-flow patients (16.1 ± 4.8 vs. 9.8 ± 5.3, P < 0.01), and was predicted by SVI (ß -0.58, P < 0.01) and PP (ß = 0.17, P < 0.01). Global CAAS was more accurate to predict low flow than Zva, systolic function and systemic vascular resistance. CONCLUSION: In patients with moderate-to-severe aortic stenosis, SVI and LV afterload-related variables were the most important determinants of 2S-ST global CAAS.

Exercise-induced pulmonary hypertension in scleroderma patients: a common finding but with elusive pathophysiology.

BACKGROUND: The etiology of exercise-induced pulmonary hypertension (exPH) in systemic sclerosis (SSc) remains a complex task, as both left ventricle (LV) diastolic dysfunction and pulmonary vascular disease can contribute to its development. We determined the incidence of exPH in SSc and examined the association between pulmonary artery systolic pressure (PASP) and tissue Doppler-derived indexes of pulmonary capillary wedge pressure (PCWP). METHODS: Thirty-eight patients with SSc were studied, using a cycloergometer protocol; 10 were excluded due to resting PH or absence of tricuspid regurgitation (TR); TR and mitral E-wave velocities, LV outflow tract time-velocity integral and LV septal E'-wave were measured before and in peak exercise to calculate cardiac output (CO), PCWP and pulmonary vascular resistance (PVR). RESULTS: Mean age of diagnosis was 57.9 ± 8.9 years. At a mean workload of 64 ± 29 Watts, 48% of patients increased PASP ≥ 50 mmHg. PCWP, assessed by the E/e' ratio, did not change significantly during exercise (10.2 ± 3.1-10.0 ± 5.1; P = NS). Only 3 patients had elevations of the E/e' ratio ≥ 13 during exercise; 2 of them had an exercise PASP ≥ 50 mmHg, yielding a proportion of exPH due to elevated LV filling pressures of 2/11 (18%). Patients with exPH had lower DLCO and had more frequently the diffuse SSc. CONCLUSION: The elevation of PASP during exercise in most patients of this cohort seems to be related to a reduced pulmonary vascular reserve, and not to an increase in PCWP. Further studies are warranted to determine the therapeutic, as well as prognostic implications of these findings.

One-shot diagnostic and prognostic assessment in intermediate- to high-risk acute pulmonary embolism: the role of multidetector computed tomography.

INTRODUCTION: Contrast-enhanced multidetector computed tomography (MDCT) is useful for the diagnosis of pulmonary embolism (PE). However, current guidelines do not support its use for risk assessment in acute PE patients. OBJECTIVES: We compared the prognostic impact of MDCT-derived indices regarding medium-term mortality in a population of intermediate- to high-risk PE patients, mostly treated by thrombolysis. METHODS: Thirty-nine consecutive patients admitted to an intensive care unit with acute PE were studied. All patients had a pulmonary MDCT on admission to the emergency room as part of the diagnostic algorithm. We assessed the following MDCT variables: right ventricular/left ventricular diameter (RV/LV) ratio, arterial obstruction index, pulmonary artery-to-aorta diameter ratio and azygos vein diameter. A 33-month follow-up was performed. RESULTS: Mean age was 59.1±19.6 years, with 80% of patients receiving thrombolysis. Follow-up all-cause mortality was 12.8%. Of the MDCT-derived variables, only the RV/LV ratio had significant predictive value, being higher in patients who suffered the endpoint (1.6±0.5 vs. 1.9±0.4, p=0.046). Patients with an RV/LV ratio ≥1.8 had 11-fold higher medium-term all-cause mortality (3.8% vs. 38.8%, p<0.001). Regarding this endpoint, the c-statistic was 0.78 (95% CI, 0.60-0.96) for RV/LV ratio and calibration was good (goodness-of-fit p=0.594). No other radiological index was predictive of mortality. CONCLUSIONS: MDCT gives the possibility, in a single imaging procedure, of diagnosing and assessing the prognosis of patients with intermediate- to high-risk PE. Although further studies are needed, the simple-to-calculate RV/LV ratio has good discrimination and calibration for predicting poorer outcomes in patients with acute PE.