Long-Term Clinical and Hemodynamic Outcomes after Heart Transplantation in Patients Pre-Treated with Sildenafil. / Resultados Clínicos e Hemodinâmicos de Longo Prazo após o Transplante de Coração em Pacientes Pré-Tratados com Sildenafil.

BACKGROUND: Elevated pulmonary vascular resistance remains a major problem for heart transplant (HT) candidate selection. OBJECTIVE: This study sought at assess the effect of pre-HT sildenafil administration in patients with fixed pulmonary hypertension. METHODS: This retrospective, single-center study included 300 consecutive, HT candidates treated between 2003 and 2013, in which 95 patients had fixed PH, and of these, 30 patients were treated with sildenafil and eventually received a transplant, forming Group A. Group B included 205 patients without PH who underwent HT. Pulmonary hemodynamics were evaluated before HT, as well as 1 week after and 1 year after HT. Survival was compared between the groups. In this study, a p value < 0.05 was considered statistically significant. RESULTS: After treatment with sildenafil but before HT, PVR (-39%) and sPAP (-10%) decreased significantly. sPAP decreased after HT in both groups, but it remained significantly higher in group A vs. group B (40.3 ± 8.0 mmHg vs 36.5 ± 11.5 mmHg, p=0.022). One year after HT, sPAP was 32.4 ± 6.3 mmHg in group A vs 30.5 ± 8.2 mmHg in group B (p=0.274). The survival rate after HT at 30 days (97% in group A versus 96% in group B), at 6 months (87% versus 93%) and at one year (80% vs 91%) were not statistically significant (Log-rank p=0.063). After this first year, the attrition rate was similar among both groups (conditional survival after 1 year, Log-rank p=0.321). CONCLUSION: In patients with severe PH pre-treated with sildenafil, early post-operative hemodynamics and prognosis are numerically worse than in patients without PH, but after 1 year, the medium to long-term mortality proved to be similar. (Arq Bras Cardiol. 2021; 116(2):219-226).

FUNDAMENTO: A resistência vascular pulmonar elevada ainda é um grande problema na seleção de candidatos ao transplante cardíaco. OBJETIVO: Nosso objetivo foi avaliar o efeito da administração de sildenafila pré-transplante cardíaco em pacientes com hipertensão pulmonar fixa. MÉTODOS: O estudo retrospectivo, de centro único, incluiu 300 candidatos a transplante cardíaco consecutivos tratados entre 2003 e 2013. Destes, 95 pacientes tinham hipertensão pulmonar fixa e, dentre eles, 30 pacientes foram tratados com sildenafila e acabaram passando pelo transplante, formando o Grupo A. O Grupo B incluiu 205 pacientes sem hipertensão pulmonar que passaram pelo transplante cardíaco. A hemodinâmica pulmonar foi avaliada antes do transplante, 1 semana e 1 ano após o transplante. A taxa de sobrevivência foi comparada entre os grupos. Neste estudo, um P valor < 0,05 foi considerado estatisticamente significativo. RESULTADOS: Após o tratamento com sildenafila, mas antes do TxC, a RVP (-39%) e a PAPs (-10%) diminuíram significativamente. A PAPs diminuiu após o TxC em ambos os grupos, mas permaneceu significativamente alta no grupo A em relação ao grupo B (40,3 ± 8,0 mmHg versus 36,5 ± 11,5 mmHg, P=0,022). Um ano após o TxC, a PAPs era 32,4 ± 6,3 mmHg no Grupo A versus 30,5 ± 8,2 mmHg no Grupo B (P=0,274). O índice de sobrevivência após o TxC 30 dias (97% no grupo A versus 96% no grupo B), 6 meses (87% versus 93%) e um ano (80% versus 91%) após o TxC não foi estatisticamente significativo (Log-rank P=0,063). Depois do primeiro ano, o índice de mortalidade era similar entre os dois grupos (sobrevivência condicional após 1 ano, Log-rank p=0,321). CONCLUSÃO: Nos pacientes com HP pré-tratados com sildenafila, a hemodinâmica pós-operatória inicial e o prognóstico são numericamente piores em pacientes sem HP, mas depois de 1 ano, a mortalidade em médio e longo prazo são semelhantes. (Arq Bras Cardiol. 2021; 116(2):219-226).

Resultados Clínicos e Hemodinâmicos de Longo Prazo após o Transplante de Coração em Pacientes Pré-Tratados com Sildenafil / Long-Term Clinical and Hemodynamic Outcomes after Heart Transplantation in Patients Pre-Treated with Sildenafil

Resumo Fundamento A resistência vascular pulmonar elevada ainda é um grande problema na seleção de candidatos ao transplante cardíaco. Objetivo Nosso objetivo foi avaliar o efeito da administração de sildenafila pré-transplante cardíaco em pacientes com hipertensão pulmonar fixa. Métodos O estudo retrospectivo, de centro único, incluiu 300 candidatos a transplante cardíaco consecutivos tratados entre 2003 e 2013. Destes, 95 pacientes tinham hipertensão pulmonar fixa e, dentre eles, 30 pacientes foram tratados com sildenafila e acabaram passando pelo transplante, formando o Grupo A. O Grupo B incluiu 205 pacientes sem hipertensão pulmonar que passaram pelo transplante cardíaco. A hemodinâmica pulmonar foi avaliada antes do transplante, 1 semana e 1 ano após o transplante. A taxa de sobrevivência foi comparada entre os grupos. Neste estudo, um P valor < 0,05 foi considerado estatisticamente significativo. Resultados Após o tratamento com sildenafila, mas antes do TxC, a RVP (-39%) e a PAPs (-10%) diminuíram significativamente. A PAPs diminuiu após o TxC em ambos os grupos, mas permaneceu significativamente alta no grupo A em relação ao grupo B (40,3 ± 8,0 mmHg versus 36,5 ± 11,5 mmHg, P=0,022). Um ano após o TxC, a PAPs era 32,4 ± 6,3 mmHg no Grupo A versus 30,5 ± 8,2 mmHg no Grupo B (P=0,274). O índice de sobrevivência após o TxC 30 dias (97% no grupo A versus 96% no grupo B), 6 meses (87% versus 93%) e um ano (80% versus 91%) após o TxC não foi estatisticamente significativo (Log-rank P=0,063). Depois do primeiro ano, o índice de mortalidade era similar entre os dois grupos (sobrevivência condicional após 1 ano, Log-rank p=0,321). Conclusão Nos pacientes com HP pré-tratados com sildenafila, a hemodinâmica pós-operatória inicial e o prognóstico são numericamente piores em pacientes sem HP, mas depois de 1 ano, a mortalidade em médio e longo prazo são semelhantes. (Arq Bras Cardiol. 2021; 116(2):219-226)

Abstract Background Elevated pulmonary vascular resistance remains a major problem for heart transplant (HT) candidate selection. Objective This study sought at assess the effect of pre-HT sildenafil administration in patients with fixed pulmonary hypertension. Methods This retrospective, single-center study included 300 consecutive, HT candidates treated between 2003 and 2013, in which 95 patients had fixed PH, and of these, 30 patients were treated with sildenafil and eventually received a transplant, forming Group A. Group B included 205 patients without PH who underwent HT. Pulmonary hemodynamics were evaluated before HT, as well as 1 week after and 1 year after HT. Survival was compared between the groups. In this study, a p value < 0.05 was considered statistically significant. Results After treatment with sildenafil but before HT, PVR (-39%) and sPAP (-10%) decreased significantly. sPAP decreased after HT in both groups, but it remained significantly higher in group A vs. group B (40.3 ± 8.0 mmHg vs 36.5 ± 11.5 mmHg, p=0.022). One year after HT, sPAP was 32.4 ± 6.3 mmHg in group A vs 30.5 ± 8.2 mmHg in group B (p=0.274). The survival rate after HT at 30 days (97% in group A versus 96% in group B), at 6 months (87% versus 93%) and at one year (80% vs 91%) were not statistically significant (Log-rank p=0.063). After this first year, the attrition rate was similar among both groups (conditional survival after 1 year, Log-rank p=0.321). Conclusion In patients with severe PH pre-treated with sildenafil, early post-operative hemodynamics and prognosis are numerically worse than in patients without PH, but after 1 year, the medium to long-term mortality proved to be similar. (Arq Bras Cardiol. 2021; 116(2):219-226)

Cardiac allograft vasculopathy: Incidence and predictors in a single-center cohort.

INTRODUCTION AND AIMS: Cardiac allograft vasculopathy (CAV) is one of the most significant complications after orthotopic heart transplantation. We aimed to investigate the incidence and predictors of CAV in a large cohort of orthotopic heart transplantation patients. METHODS: We conducted a retrospective analysis on a prospective cohort of 233 patients who underwent transplantation between November 2003 and May 2014. Baseline clinical data and invasive coronary angiograms (n=712) performed as part of the follow-up program were analyzed by two independent investigators. RESULTS: We included 157 male and 45 female patients with a median age of 66 years. A third of patients had previous ischemic heart disease, 30% peripheral arterial disease, 37% hypertension and 47% dyslipidemia, and 17% were smokers. Acute moderate or severe rejection occurred in 42 patients during the first year. Over a median follow-up of 2920 days, 18% were diagnosed with CAV, with an incidence of 2.91 cases per 100 person-years. Predictors of CAV were previous ischemic heart disease (HR 2.32, 95% CI 1.21-4.45, p=0.01), carotid artery disease (HR 2.44, 95% CI 1.27-4.71, p<0.01), and donor age (HR 1.04, 95% CI 1.00-1.07, p=0.01). CONCLUSION: In a single-center cohort of orthotopic heart transplantation patients, predictors of CAV were previous ischemic heart disease, carotid artery disease and donor age.

Renal artery wall 18F-NaF activity and glomerular filtration rate: an exploratory analysis in a high cardiovascular risk population.

OBJECTIVES: Atherosclerotic plaque molecular imaging with F-sodium fluoride (NaF) PET with computed tomography (PET-CT) may identify active unstable microcalcification. We sought to explore renal arteries calcification activity in a group of high cardiovascular (CV) risk subjects without manifest CV disease. METHODS: High CV risk hypertensive individuals from a single centre were prospectively scanned with F-NaF-PET-CT in major vascular territories. Renal arterial wall activity was retrospectively analysed and expressed as the ratio between maximum standard uptake value in the lesion and mean blood pool activity in the superior vena cava [tissue-to-background ratio (TBR)]. We explored renal artery wall F-NaF activity's association to CV risk factors and renal function. RESULTS: Mean age was 64 ± 8.6 years, 56% male, 96% Caucasian and 24% had chronic kidney disease (CKD) (n = 25). Six individuals (24%) showed renal artery wall radiotracer uptake (TBR 1.4 ± 0.4); these subjects were heavier, had higher triglycerides, high-sensitivity C-reactive protein and predicted CV risk (SCORE) compared to the remaining cohort (P < 0.05 for all comparisons). There was a trend toward higher F-NaF uptake in other major vessels and increased thoracic fat volume in subjects with renal artery wall uptake. Glomerular filtration rate (GFR) was lower in subjects with positive renal plaques (93.0 ± 29.7 vs. 65.0 ± 19.7 ml/min, P = 0.04). Renal artery radiotracer uptake and eGFR were inversely correlated (r = -0.42, P = 0.04). CONCLUSION: In a high CV risk group without manifest CV disease, higher renal artery wall F-NaF activity is associated with superior predicted CV risk and lower GFR.

Keeping prognostic assessment simple: The value of clinical features in normotensive cancer patients with pulmonary embolism.

INTRODUCTION: Although normotensive cancer patients with acute pulmonary embolism (PE) are a heterogeneous population, most validated clinical prognostic scores classify these patients as high-risk individuals, which limits their usefulness in this setting. In this study, we aimed to identify readily available clinical predictors of overall 30-day and one-year mortality in normotensive cancer patients with PE. METHODS AND RESULTS: We performed a retrospective single-center study that included all normotensive cancer patients with PE diagnosed by multidetector computed tomography (MDCT) during emergency department stay between January 2010 and December 2011. Clinical, MDCT and laboratory variables were collected for all patients. A total of 69 patients were included. All-cause mortality was 28% and 55% at 30 days and one year of follow-up, respectively. Lower mean arterial pressure, higher lactate level and a higher Shock Index (SI) at hospital admission were associated with increased all-cause mortality at 30 days and one year of follow-up. The simplified Pulmonary Embolism Severity Index was not a predictor of short- or long-term mortality. An SI of ≥0.7 was found to be associated with lower event-free survival in both short- and long-term follow-up (hazard ratio 7.20 [95% CI, 1.66-31.21, p<0.01] and 3.51 [95% CI, 1.70-7.25, p<0.01], respectively). CONCLUSIONS: This is the first article reporting the value of the SI, a user-friendly and readily available clinical tool, as an independent and accurate predictor of 30-day and one-year all-cause mortality in normotensive cancer patients with symptomatic PE.

Early manifestation of myocardial involvement in systemic sclerosis.

INTRODUCTION: Systemic sclerosis (SSc) is a systemic autoimmune disease involving multiple organs. We present a rare case of SSc in which clinical manifestations of cardiac fibrosis occurred early in the disease course. CASE REPORT: We report the case of a 40-year-old Caucasian man, previously diagnosed with SSc, who presented with decompensated heart failure. Transthoracic echocardiography was remarkable for severe right ventricular systolic dysfunction, abnormal ventricular septal motion, severe functional tricuspid regurgitation and normal pulmonary artery systolic pressure. Left ventricular ejection fraction was 45%. Right heart catheterization revealed no signs of pulmonary hypertension. Cardiac magnetic resonance (CMR) showed diffuse myocardial infiltration, later confirmed as myocardial fibrosis by endomyocardial biopsy. CONCLUSIONS: Myocardial fibrosis is an important cause of early heart failure in SSc patients and is associated with poor prognosis. Echocardiography and CMR help establish the diagnosis and enable an appropriate therapeutic strategy to be developed in such cases.

An Alternative Method to Calculate Simplified Projected Aortic Valve Area at Normal Flow Rate.

BACKGROUND: Simplified projected aortic valve area (EOAproj) is a valuable echocardiographic parameter in the evaluation of low flow low gradient aortic stenosis (LFLG AS). Its widespread use in clinical practice is hampered by the laborious process of flow rate (Q) calculation. OBJETIVE: This study proposes a less burdensome, alternative method of Q calculation to be incorporated in the original formula of EOAproj and measures the agreement between the new proposed method of EOAproj calculation and the original one. METHODS: Retrospective observational single-institution study that included all consecutive patients with classic LFLG AS that showed a Q variation with dobutamine infusion ≥ |15|% by both calculation methods. RESULTS: Twenty-two consecutive patients with classical LFLG AS who underwent dobutamine stress echocardiography were included. Nine patients showed a Q variation with dobutamine infusion calculated by both classical and alternative methods ≥ |15|% and were selected for further statistical analysis. Using the Bland-Altman method to assess agreement we found a systematic bias of 0,037 cm2 (95% CI 0,004 - 0,066), meaning that on average the new method overestimates the EOAproj in 0,037 cm2 compared to the original method. The 95% limits of agreement are narrow (from -0,04 cm2 to 0,12 cm2), meaning that for 95% of individuals, EOAproj calculated by the new method would be between 0,04 cm2 less to 0,12 cm2 more than the EOAproj calculated by the original equation. CONCLUSION: The bias and 95% limits of agreement of the new method are narrow and not clinically relevant, supporting the potential interchangeability of the two methods of EOAproj calculation. As the new method requires less additional measurements, it would be easier to implement in clinical practice, promoting an increase in the use of EOAproj.

An Alternative Method to Calculate Simplified Projected Aortic Valve Area at Normal Flow Rate / Um Método Alternativo para o Cálculo da Área Valvular Aórtica Projetada Simplificada em Uma Taxa de Fluxo Normal

Abstract Background: Simplified projected aortic valve area (EOAproj) is a valuable echocardiographic parameter in the evaluation of low flow low gradient aortic stenosis (LFLG AS). Its widespread use in clinical practice is hampered by the laborious process of flow rate (Q) calculation. Objetive: This study proposes a less burdensome, alternative method of Q calculation to be incorporated in the original formula of EOAproj and measures the agreement between the new proposed method of EOAproj calculation and the original one. Methods: Retrospective observational single-institution study that included all consecutive patients with classic LFLG AS that showed a Q variation with dobutamine infusion ≥ -15-% by both calculation methods. Results: Twenty-two consecutive patients with classical LFLG AS who underwent dobutamine stress echocardiography were included. Nine patients showed a Q variation with dobutamine infusion calculated by both classical and alternative methods ≥ -15-% and were selected for further statistical analysis. Using the Bland-Altman method to assess agreement we found a systematic bias of 0,037 cm2 (95% CI 0,004 - 0,066), meaning that on average the new method overestimates the EOAproj in 0,037 cm2 compared to the original method. The 95% limits of agreement are narrow (from -0,04 cm2 to 0,12 cm2), meaning that for 95% of individuals, EOAproj calculated by the new method would be between 0,04 cm2 less to 0,12 cm2 more than the EOAproj calculated by the original equation. Conclusion: The bias and 95% limits of agreement of the new method are narrow and not clinically relevant, supporting the potential interchangeability of the two methods of EOAproj calculation. As the new method requires less additional measurements, it would be easier to implement in clinical practice, promoting an increase in the use of EOAproj.

Resumo Fundamento: A área valvular aórtica projetada simplificada (AEOproj) é um parâmetro ecocardiográfico valioso na avaliação da estenose aórtica de baixo fluxo e baixo gradiente (EA BFBG). Sua utilização na prática clínica é limitada pelo trabalhoso processo de cálculo da taxa de fluxo (Q). Objetivos: Este estudo propõe um método alternativo, menos complexo, para o cálculo da Q para ser incorporado na fórmula original da AEOproj, e mede a concordância entre o novo método proposto para o cálculo da AEOproj em comparação ao método original. Métodos: Estudo retrospectivo, observacional, unicêntrico que incluiu todos os pacientes com AE BFBG clássica com variação da Q com infusão de dobutamina ≥ -15-% por ambos os métodos. Resultados: Foram incluídos 22 pacientes consecutivos com AE BFBG clássico, que se submeteram à ecocardiografia sob estresse com dobutamina. Nove pacientes apresentaram uma variação da Q com infusão de dobutamina calculada tanto pelo método clássico como pelo método alternativo ≥ -15-%, e foram selecionados para análise estatística. Utilizando método Bland-Altman para avaliar a concordância, encontramos um viés sistemático de 0,037 cm2 (IC 95% 0,004 - 0,066), o que significa que, em média, o novo método superestima a AEOproj em 0m037 cm2 em comparação ao método original. Os limites de concordância de 95% são estreitos (de -0,04 cm2 a 0,12 cm2), o que significa que para 95% dos indivídios, a AEOproj calculada pelo novo método estaria entre 0,04 cm2 menos a 0,12 cm2 mais que a AEOproj calculada pela equação original. Conclusão: O viés e os limites de 95% de concordância do novo método são estreitos e não são clinicamente relevantes, o que corrobora a intercambialidade dos dois métodos de cálculo da AEOproj. Uma vez que o novo método requer menos medidas, seria mais fácil de ser implementado na prática clínica, promovendo um aumento na utilização da AEOproj.

Assessment of atherosclerotic plaque calcification using F18-NaF PET-CT.

BACKGROUND: The aim of the present study was to evaluate the uptake of F18-NaF by the arterial wall in patients with high cardiovascular (CV) risk profile. The tracer uptake was assessed in relation to gender and the number of CV risk factors. METHODS AND RESULTS: 25 patients without known CV disease were included and evaluated by PET-CT with F18-NaF: 14 (56%) men and 11 (44%) women. The mean target-to-background ratio (TBR: max SUV/mean blood-pool SUV) but not the corrected uptake per lesion (CUL: max SUV - mean blood-pool SUV) was higher in men than women (TBR: 1.8 ± 0.6 vs 1.7 ± 0.2; P = 0.04; CUL: 0.7 ± 0.3 vs W 0.6 ± 0.1; P = 0.4). Patients with >3 CV risk factors had higher CUL (0.8 ± 0.1 vs 0.6 ± 0.2; P = 0.01) but not TBR (1.8 ± 0.2 vs 1.7 ± 0.6; P = 0.7) than patients with <3 risk factors. CONCLUSIONS: The TBR but not CUL is higher in men than women while the CUL but not TBR is related to the number of CV risk factors. These results are hypothesis-generating and require validation in larger studies.

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.

Two-dimensional speckle-tracking global longitudinal strain in high-sensitivity troponin-negative low-risk patients with unstable angina: a "resting ischemia test"?

With the introduction of high-sensitivity troponin (hsTNI) assays, the clinical significance unstable angina (UA) has become uncertain. We hypothesized that impaired left ventricular (LV) two-dimensional speckle-tracking echocardiography (2D-STE)-derived peak global longitudinal strain (GLS) was able to exclude the presence of significant coronary artery disease (CAD) in UA patients without prior cardiovascular (CV) events and with a normal LV ejection fraction (LVEF). From a cohort of 200 patients admitted with UA, we selected 61 patients without prior CV events and with a normal LVEF; of these, 48 (79%) underwent invasive coronary angiography (ICA) and 24 (39%) had at least ≥ 1 significant stenosis. 2D-STE LV GLS analysis was performed offline using a dedicated automated software program. The mean patient age was 61 ± 12 years and 66% were male. Among the 48 patients selected to undergo ICA, those without significant CAD had a better 2D-STE GLS (- 19.4 vs. - 15.9%, P < 0.001). A cutoff of - 17.5% had a sensitivity of 87% and a specificity of 82% for differentiating UA patients without significant stenosis (AUC 0.86, P < 0.001). Patients who did not undergo ICA had a better GLS (- 20.2 vs. - 17.7%, P = 0.017). 2D-STE GLS had a significantly better discriminative power compared with LVEF (P < 0.001) and the GRACE score (P < 0.001) for identifying patients with significant CAD. Impaired values of 2D-STE LV GLS were significantly associated with the presence of CAD in hsTnI-negative UA patients and demonstrated better discriminative power than LVEF and the GRACE score.

Early, real-world experience with direct oral anticoagulants in the treatment of intermediate-high risk acute pulmonary embolism.

INTRODUCTION: Intermediate-high risk pulmonary embolism (IHR-PE) has a poor prognosis, but is under-represented in trials of direct oral anticoagulants (DOACs) in venous thromboembolic disease (VTE). We aimed to assess whether the administration of DOACs was equivalent to the conventional (CONV) treatment of low-molecular weight heparin bridged with warfarin for treating IHR-PE. METHODS: We conducted a retrospective cohort study including 59 consecutive patients admitted with IHR-PE and followed for up to three months after discharge. Two groups were created based on the anticoagulant strategy: CONV (n=35) and DOAC (n=24). The efficacy endpoints were death, recurrent PE, estimated pulmonary artery systolic pressure (PASP), right ventricular systolic function (RVSF) at discharge, and length of stay; the safety endpoint was major bleeding. RESULTS: The two groups were similar regarding demographics, PE etiology and markers of clinical severity. There were four in-hospital deaths in the CONV group and none in the DOAC group. No recurrent PE or major bleeding event was recorded in either group. At discharge, neither PASP nor RVSF was different between the groups. Patients in the DOAC group were discharged 1.7 days earlier on average than patients in the CONV group (4.7±2.4 vs. 3.0±1.5 days, p=0.002). CONCLUSIONS: The adoption of a DOAC treatment strategy in this real-world cohort of IHR-PE patients was associated with similar efficacy and safety to the CONV approach. The fact that monitoring of anticoagulation effect was unnecessary probably led to the significant reduction in length of stay.

Atherosclerotic plaque metabolism in high cardiovascular risk subjects - A subclinical atherosclerosis imaging study with 18F-NaF PET-CT.

BACKGROUND AND AIMS: Atherosclerotic plaque molecular imaging with 18F-sodium fluoride (NaF) in positron emission tomography with computed tomography (PET-CT) provides potential discrimination between active unstable microcalcification and established dormant calcification. We aimed to study 18F-NaF atherosclerotic plaque uptake in high cardiovascular (CV) risk participants and its associations with CV risk factors, coronary calcium score and thoracic fat volume. METHODS: High CV risk hypertensive individuals from a single centre were prospectively scanned with 18F-NaF-PET-CT in the coronary, aortic and carotideal arteries. Atherosclerotic plaque 18F-NaF uptake was expressed as Corrected Uptake per Lesion (CUL): maximum standard uptake value in each vascular territory subtracted by mean blood pool activity. RESULTS: Mean age was 64 years, 56% male and 96% Caucasian (n = 25). Ninety six per cent of the subjects showed 18F-NaF uptake in the aorta (CUL 0.9 ± 0.3), 40% in the carotid arteries (median CUL 0.0, IQR 0.0-0.7) and 64% in the coronary arteries (0.4, IQR 0.0-0.6). Individuals with ≥ five risk factors (60%) had increased overall 18F-NaF uptake (1.1 ± 0.3 vs. 0.7 ± 0.3, p < 0.01), which was positively correlated with predicted fatal CV risk - SCORE (r = 0.49, p = 0.01). There was no correlation between 18F-NaF uptake in the coronary arteries and calcium score (p = 0.87). Thoracic fat was moderately correlated with overall CUL (r = 0.41, p = 0.04). CONCLUSIONS: In a high CV risk group, 18F-NaF atherosclerotic plaque uptake was related to the burden of CV risk factors and thoracic fat volume, but there was no association between coronary uptake and calcium score.

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.