Peripheral microvascular function is linked to cardiac involvement on cardiovascular magnetic resonance in systemic sclerosis-related pulmonary arterial hypertension.

AIMS: Systemic sclerosis (SSc) is characterized by vasculopathy, inflammation, and fibrosis, and carries one of the worst prognoses if patients also develop pulmonary arterial hypertension (PAH). Although PAH is a known prognosticator, patients with SSc-PAH demonstrate disproportionately high mortality, presumably due to cardiac involvement. In this cross-sectional study, the relationship between cardiac involvement revealed by cardiovascular magnetic resonance (CMR) and systemic microvascular disease severity measured with nailfold capillaromicroscopy (NCM) in patients with SSc-PAH is evaluated and compared with patients with idiopathic PAH (IPAH). METHODS AND RESULTS: Patients with SSc-PAH and IPAH underwent CMR, echocardiography, and NCM with post-occlusive reactivity hyperaemia (PORH) testing on the same day. CMR imaging included T2 (oedema), native, and post-contrast T1 mapping to measure the extracellular volume fraction (ECV, fibrosis) and adenosine-stress-perfusion imaging measuring the relative myocardial upslope (microvascular coronary perfusion). Measures of peripheral microvascular function were related to CMR indices of oedema, fibrosis, and myocardial perfusion. SSc-PAH patients (n = 20) had higher T2 values and a trend towards a higher ECV, compared with IPAH patients (n = 5), and a lower nailfold capillary density (NCD) and reduced capillary recruitment after PORH. NCD correlated with ECV and T2 (r = -0.443 and -0.464, respectively, P < 0.05 for both) and with markers of diastolic dysfunction on echocardiography. PORH testing, but not NCD, correlated with the relative myocardial upslope (r = 0.421, P < 0.05). CONCLUSION: SSc-PAH patients showed higher markers of cardiac fibrosis and inflammation, compared with IPAH patients. These markers correlated well with peripheral microvascular dysfunction, suggesting that SSc-driven inflammation and vasculopathy concurrently affect peripheral microcirculation and the heart. This may contribute to the disproportionate high mortality in SSc-PAH.

Thioredoxin system activation is associated with the progression of experimental pulmonary arterial hypertension.

In addition to being an antioxidant, thioredoxin (Trx) is known to stimulate signaling pathways involved in cell proliferation and to inhibit apoptosis. The aim of this study was to explore the role of Trx in some of these pathways along the progression of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male rats were first divided into two groups: monocrotaline (MCT - 60 mg/kg i.p.) and control (received saline), that were further divided into three groups: 1, 2, and 3 weeks. Animals were submitted to echocardiographic analysis. Right and left ventricles were used for the measurement of hypertrophy, through morphometric and histological analysis. The lung was prepared for biochemical and molecular analysis. One week after MCT injection, there was an increase in thioredoxin reductase (TrxR) activity, a reduction in glutathione reductase (GR) activity, and an increase in Trx-1 and vitamin D3 up-regulated protein-1 (VDUP-1) expression. Two weeks after MCT injection, there was an increase in VDUP-1, Akt and cleaved caspase-3 activation, and a decrease in Trx-1 and Nrf2 expression. PAH-induced by MCT promoted a reduction in Nrf2 and Trx-1 expression as well as an increase in Akt and VDUP-1 expression after three weeks. The increase in pulmonary vascular resistance was accompanied by increased TrxR activity, suggesting an association between the Trx system and functional changes in the progression of PAH. It seems that Trx-1 activation was an adaptive response to MCT administration to cope with pulmonary remodeling and disease progression, suggesting a potential new target for PAH therapeutics.

Lessons from Cancer Metabolism for Pulmonary Arterial Hypertension and Fibrosis.

Metabolism is essential for a living organism to sustain life. It provides energy to a cell by breaking down compounds (catabolism) and supplies building blocks for the synthesis of macromolecules (anabolism). Signal transduction pathways tightly regulate mammalian cellular metabolism. Simultaneously, metabolism itself serves as a signaling pathway to control many cellular processes, such as proliferation, differentiation, cell death, gene expression, and adaptation to stress. Considerable progress in the metabolism field has come from understanding how cancer cells co-opt metabolic pathways for growth and survival. Recent data also show that several metabolic pathways may participate in the pathogenesis of lung diseases, some of which could be promising therapeutic targets. In this translational review, we will outline the basic metabolic principles learned from the cancer metabolism field as they apply to the pathogenesis of pulmonary arterial hypertension and fibrosis and will place an emphasis on therapeutic potential.

Conducción anestésica perioperatoria en gestante a término con hipertensión pulmonar idiopática / Perioperative anesthetic management in term pregnant women with idiopathic pulmonary hypertension

Introducción: La hipertensión arterial pulmonar es una enfermedad con una baja incidencia en la gestante, aunque trae consigo una alta mortalidad una vez presentada. Un diagnóstico oportuno y un manejo perioperatorio adecuado minimizan el riesgo de desenlace fatal tanto para la madre como el feto. Objetivo: Describir el comportamiento de la hipertensión arterial pulmonar en la gestante a término y su conducción anestésica. Presentación del caso: Paciente de 23 años, antecedentes de salud, edad gestacional de 35.2 semanas. Luego de presentar dolor de espalda y ardor en el pecho relacionado con el esfuerzo, palpitaciones, disnea y bloqueo de rama derecha en electrocardiograma, se ingresa en UTI con sospecha de tromboembolismo pulmonar, el cual queda descartado tras diagnóstico confirmatorio de hipertensión pulmonar después de realizar angio TAC y ecocardiografía. Se decide realizar cesárea programada bajo técnica regional peridural, sin complicaciones tanto para la madre como el niño. Después de 2 días bajo vigilancia intensiva se traslada a su centro hospitalario de cabecera. Conclusiones: La vía del parto, así como una elección adecuada de la técnica anestésica, puede ser la diferencia entre el éxito y la fatalidad. Las técnicas regionales suelen recomendarse por encima de la técnica de anestesia general siempre que no se presenten contraindicaciones(AU)

Introduction: Pulmonary arterial hypertension is a disease with low incidence in the pregnant woman, although it brings about high mortality once presented. Timely diagnosis and adequate perioeprative management minimize the risk of fatal outcome for both mother and fetus. Objective: To describe pulmonary arterial hypertension and its anesthetic management in the term pregnant woman. Case presentation: 23-year-old female patient, with health history and gestational age of 35.2 weeks. After presenting back pain and chest burning associated with exertion, palpitations, dyspnea and right bundle branch block in the electrocardiogram, the patient was admitted to the intensive care unit with suspected pulmonary thromboembolism, which was ruled out due to the confirmatory diagnosis of pulmonary hypertension after performing computerized tomography angiography and echocardiography. Scheduled cesarean section was decided to be perform using the regional peridural technique, without complications for both the mother and the child. After two days under intensive surveillance, she was transferred to her primary hospital. Conclusions: The route of delivery, as well as an adequate choice of the anesthetic technique, can be the difference between success and fatality. Regional techniques are usually recommended over the general anesthesia technique, as long as there are no contraindications(AU)

Change of right ventricular systolic pressure can indicate dasatinib-induced pulmonary arterial hypertension in chronic myeloid leukemia.

BACKGROUND: We investigated the feasibility of the clinical application of non-invasive transthoracic echocardiography for diagnosis of pulmonary arterial hypertension induced by dasatinib (D-PAH) in chronic myeloid leukemia (CML). METHODS: A total of 451 CML patients who were examined by 2D-echocardiography at least once at baseline and/or during dasatinib therapy as frontline (n = 196) and subsequent line (n = 255) therapies were included in this study. D-PAH was defined as right ventricular systolic pressure (RVSP) >40 mm Hg with relevant symptoms and the absence of other specific etiologies. RESULTS: A total of 847 echocardiographies were performed including at baseline (n = 255) and during dasatinib treatment (n = 592). During the median of 36.2 (0.1-181.8) months of dasatinib therapy, the level of RVSP gradually increased (Spearman's r = 0.2819, p < 0.001) and the mean RVSP was significantly increased after taking dasatinib therapy compared with baseline. During dasatinib therapy, 56 (12.4%) patients had RVSP >40 mm Hg without (asymptomatic, n = 27, 48.2%) or with symptoms (D-PAH, n = 29, 51.8%). All asymptomatic patients maintained dasatinib therapy without further symptoms and the D-PAH patients ultimately switched to other tyrosine kinase inhibitors. After dasatinib discontinuation, 13 (45%) and 15 (52%) patients showed RVSP normalization and gradual decrease, respectively. CONCLUSIONS: Our large cohort study demonstrated that the gradual increment of RVSP might be induced by dasatinib and non-invasive echocardiography can be fast way for early diagnosis as well as for monitoring of D-PAH.

Evaluation of right coronary vascular dysfunction in severe pulmonary hypertensive rats using synchrotron radiation microangiography.

Pulmonary hypertension (PH) causes cardiac hypertrophy in the right ventricle (RV) and eventually leads to RV failure due to persistently elevated ventricular afterload. We hypothesized that the mechanical stress on the RV associated with increased afterload impairs vasodilator function of the right coronary artery (RCA) in PH. Coronary vascular response was assessed using microangiography with synchrotron radiation (SR) in two well-established PH rat models, monocrotaline injection or the combined exposure to chronic hypoxia and vascular endothelial growth factor receptor blockade with Su5416 (SuHx model). In the SuHx model, the effect of the treatment with the nonselective endothelin-1 receptor antagonist (ERA), macitentan, was also examined. Myocardial viability was determined in SuHx model rats, using 18F-FDG Positron emission tomography (PET) and magnetic resonance imaging (MRI). Endothelium-dependent and endothelium-independent vasodilator responses were significantly attenuated in the medium and small arteries of severe PH rats. ERA treatment significantly improved RCA vascular function compared with the untreated group. ERA treatment improved both the decrease in ejection fraction and the increased glucose uptake, and reduced RV remodeling. In addition, the upregulation of inflammatory genes in the RV was almost suppressed by ERA treatment. We found impairment of vasodilator responses in the RCA of severe PH rat models. Endothelin-1 activation in the RCA plays a major role in impaired vascular function in PH rats and is partially restored by ERA treatment. Treatment of PH with ERA may improve RV function in part by indirectly attenuating right heart afterload and in part by associated improvements in right coronary endothelial function.NEW & NOTEWORTHY We demonstrated for the first time the impairment of vascular responses in the right coronary artery (RCA) of the dysfunctional right heart in pulmonary hypertensive rats in vivo. Treatment with an endothelin-1 receptor antagonist ameliorated vascular dysfunction in the RCA, enabled tissue remodeling of the right heart, and improved cardiac function. Our results suggest that impaired RCA function might also contribute to the early progression to heart failure in patients with severe pulmonary arterial hypertension (PAH). The endothelium of the coronary vasculature might be considered as a potential target in treatments to prevent heart failure in severe patients with PAH.

A novel unidirectional-valved shunt approach for end-stage pulmonary arterial hypertension: Early experience in adolescents and adults.

OBJECTIVES: Despite advances in treatment of idiopathic pulmonary arterial hypertension (IPAH), there remains no medical cure, and patients can experience disease progression leading to right heart failure, progressive exercise intolerance, and death. The reversed Potts shunt (left pulmonary artery to descending aorta) was reintroduced for treatment of end-stage IPAH to permit decompression of the suprasystemic right ventricle by right to left shunting, with preservation of upper body oxygenation. The shunt has the potential to delay the need for lung transplantation and offer a treatment for those who are transplant ineligible. To optimize shunt design and avoid the potential complications of bidirectional shunting, we developed a novel approach using a unidirectional-valved shunt (UVS) in patients with IPAH with suprasystemic pulmonary arterial pressure and poor right ventricular function. METHODS: A single-center retrospective review was performed of UVS cases done at Columbia University Medical Center-New York Presbyterian between November 1, 2016, and May 1, 2019. RESULTS: Five patients (4 female; ages 12-22 years) underwent UVS. All had suprasystemic pulmonary arterial pressure, poor right ventricular function, and World Health Organization functional class IV symptoms at baseline. All patients are alive and transplant-free at latest follow-up (range 3-33 months; median 6 ± 11 months). CONCLUSIONS: The UVS may offer an alternative solution to lung transplantation in adolescents and young adults with IPAH. Longer-term follow-up is needed to determine the ultimate impact of unidirectional unloading of the right ventricle in these patients and to determine whether the UVS will enable a broader approach to the treatment of patients with IPAH.

"Pure" severe aortic stenosis without concomitant valvular heart diseases: echocardiographic and pathophysiological features.

PURPOSE: In echocardiography the severity of aortic stenosis (AS) is defined by effective orifice area (EOA), mean pressure gradient (mPGAV) and transvalvular flow velocity (maxVAV). The hypothesis of the present study was to confirm the pathophysiological presence of combined left ventricular hypertrophy (LVH), diastolic dysfunction (DD) and pulmonary artery hypertension (PAH) in patients with "pure" severe AS. METHODS AND RESULTS: Patients (n = 306) with asymptomatic (n = 133) and symptomatic (n = 173) "pure" severe AS (mean age 78 ± 9.5 years) defined by indexed EOA < 0.6 cm2 were enrolled between 2014 and 2016. AS patients were divided into 4 subgroups according to mPGAV and indexed left ventricular stroke volume: low flow (LF) low gradient (LG)-AS (n = 133), normal flow (NF) LG-AS (n = 91), LF high gradient (HG)-AS (n = 21) and NFHG-AS (n = 61). Patients with "pure" severe AS showed mean mPGAV of 31.7 ± 9.1 mmHg and mean maxVAV of 3.8 ± 0.6 m/s. Only 131 of 306 patients (43%) exhibited mPGAV > 40 mmHg and maxVAV > 4 m/s documenting incongruencies of the AS severity assessment by Doppler echocardiography. LVH was documented in 81%, DD in 76% and PAH in 80% of AS patients. 54% of "pure" AS patients exhibited all three alterations. Ranges of mPGAV and maxVAV were higher in patients with all three alterations compared to patients with less than three. 224 (73%) patients presented LG-conditions and 82 (27%) HG-conditions. LVH was predominant in NF-AS (p = 0.014) and PAH in LFHG-AS (p = 0.014). Patients' treatment was retrospectively assessed (surgery: n = 100, TAVI: n = 48, optimal medical treatment: n = 156). CONCLUSION: In patients with "pure" AS according to current guidelines the presence of combined LVH, DD and PAH as accepted pathophysiological sequelae of severe AS cannot be confirmed. Probably, the detection of these secondary cardiac alterations might improve the diagnostic algorithm to avoid overestimation of AS severity.

Tumor Necrosis Factor Induces Obliterative Pulmonary Vascular Disease in a Novel Model of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.

OBJECTIVE: Connective tissue disease (CTD)-associated pulmonary arterial hypertension (PAH) is the second most common etiology of PAH and carries a poor prognosis. Recently, it has been shown that female human tumor necrosis factor (TNF)-transgenic (Tg) mice die of cardiopulmonary disease by 6 months of age. This study was undertaken to characterize this pathophysiology and assess its potential as a novel model of CTD-PAH. METHODS: Histologic analysis was performed on TNF-Tg and wild-type (WT) mice to characterize pulmonary vascular and right ventricular (RV) pathology (n = 40 [4-5 mice per group per time point]). Mice underwent right-sided heart catheterization (n = 29) and micro-computed tomographic angiography (n = 8) to assess vascular disease. Bone marrow chimeric mice (n = 12), and anti-TNF-treated mice versus placebo-treated mice (n = 12), were assessed. RNA sequencing was performed on mouse lung tissue (n = 6). RESULTS: TNF-Tg mice displayed a pulmonary vasculopathy marked by collagen deposition (P < 0.001) and vascular occlusion (P < 0.001) with associated RV hypertrophy (P < 0.001) and severely increased RV systolic pressure (mean ± SD 75.1 ± 19.3 mm Hg versus 26.7 ± 1.7 mm Hg in WT animals; P < 0.0001). TNF-Tg mice had increased α-smooth muscle actin (α-SMA) staining, which corresponded to proliferation and loss of von Willebrand factor (vWF)-positive endothelial cells (P < 0.01). There was an increase in α-SMA-positive, vWF-positive cells (P < 0.01), implicating endothelial-mesenchymal transition. Bone marrow chimera experiments revealed that mesenchymal but not bone marrow-derived cells are necessary to drive this process. Treatment with anti-TNF therapy halted the progression of disease. This pathology closely mimics human CTD-PAH, in which patient lungs demonstrate increased TNF signaling and significant similarities in genomic pathway dysregulation. CONCLUSION: The TNF-Tg mouse represents a novel model of CTD-PAH, recapitulates key disease features, and can serve as a valuable tool for discovery and assessment of therapeutics.

Normalization of the right heart and the preoperative factors that influence the emergence PAH after surgical closure of atrial septal defect.

BACKGROUND: Surgical closure of atrial septal defect (ASD) is contraindicated in the condition with severe pulmonary arterial hypertension (PAH), whereas ASD closure in an effective intervention to normalize the structure and function of the right heart after previously experiencing volume overload due to shunting from the defect. This study aimed to evaluate normalization of the right heart and emergence of PAH after surgical closure of ASD. METHODS: This retrospective study was carried out in 45 patients over 18 years who had undergone surgical closure of ASD. The study has the aim to evaluate the morphological and functional parameters before and after the surgical approach and the preoperative factors that influenced the development of pulmonary arterial hypertension (PAP) after the ASD closure. RESULTS: The majority of subjects were female (73.3%) although there were no significant differences between males and females from the various parameters. The average of mPAP in the group that experienced PAH was higher than non-PAH group after ASD closure (p = 0.019, 31.23 ± 12.70 mmHg vs 24.07 ± 13.08 mmHg). Significant differences were found in the Right Atrium (RA) dimension, Right Ventricle (RV) dimension, Tricuspid Regurgitation Velocity (TRV) and Tricuspid Annular Plane Systolic Excursion (TAPSE) between before and at 6 months after ASD closure (p = 0.000, p = 0.000, p = 0.000, p = 000, respectively). The sensitivity of the predictive model to estimate PAH at 6 months after surgical closure of ASD was 58%, with a specificity of 62.5%. CONCLUSION: Structural and functional normalization of the right heart occurs at 6 months after surgical closure of ASD with the decrease of RA and RV dimensions and improvement from tricuspid regurgitation. Emergence of PAH after ASD closure was influenced by higher mPAP before surgical approach.

Image diagnosis: Eisenmenger's syndrome in patients with simple congenital heart disease.

BACKGROUND: Early identification of congenital heart disease (CHD) allows detection of the pulmonary arteriopathy in an early stage, and timely shunt closure can permanently reverse pulmonary arterial hypertension (PAH). However, surgical correction is not recommended in patients with irreversible PAH. Herein we report our experience about Eisenmenger's syndrome in simple CHD. CASE PRESENTATION: From January 2017 to November 2018, a total of 8 CHD patients (3 ventricular septal defects (VSD), 2 atrial septal defects (ASD), and 3 patent ductus arteriosus (PDA), median age, 15.5 years [range, 3-18 years]) with PAH were detected by chest X-ray, electrocardiogram, transthoracic echocardiography (TTE), computed tomographic angiography (CTA) and cardiac catheterization. The median defect diameter, pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR) were 16.5 mm (range, 3-30 mm), 75 mmHg (range, 60-86 mmHg), and 16 Woods units (range, 12-19 Woods units), respectively. Here, we report the representative cases of three types of simple CHD with irreversible PAH. The surgical correction was not performed in all patients who had fixed PAH and were referred to medical treatment. CONCLUSIONS: PAH in CHD can be reversed by early shunt closure, but this potential is lost beyond a certain point of no return. This article highlights the essence of enhancing the level of healthcare and services in Chinese rural areas. Failure to accurately and timely assess PAH will delay effective treatment past optimal treatment time, and even lead to death.

Assessment of lung glucose uptake in patients with systemic lupus erythematosus pulmonary arterial hypertension: a quantitative FDG-PET imaging study.

PURPOSE: Pulmonary arterial hypertension (PAH) is a recognized complication of systemic lupus erythematosus (SLE-PAH) patients and its lung pathology shares similarity to idiopathic PAH (IPAH) with distinctive inflammatory feature. FDG-PET reports glucose metabolism from both hyperproliferative and inflammatory cellular elements of vascular pathology in PAH. We explored the application of FDG-PET in reporting SLE-PAH pulmonary vascular pathology. METHODS: Sixty-minute dynamic FDG-PET imaging was applied in 14 SLE-PAH patients, 20 IPAH patients and 10 healthy volunteers. Patlak analysis was used to quantify lung FDG uptake (influx rate Ki). RESULTS: Mean lung FDG uptake in SLE-PAH (Ki 0.00714 ± 0.000602 mL/g/min) was significantly higher than that of the healthy volunteers (Ki 0.000262 ± 0.000168 mL/g/min) (p < 0.05). SLE-PAH patients with SLE disease activity score SLEDAI ≥ 5 demonstrated significantly increased lung FDG uptake (Ki 0.001075 ± 0.00055 mL/g/min) than those with SLEDAI < 5 (Ki 0.000233 ± 0.00017 mL/g/min) (p = 0.0038) and IPAH (Ki 0.000524 ± 0.000314 mL/g/min) (p = 0.0025). Lung FDG uptake in SLE-PAH correlated with SLEDAI score and plasma complement C3 and C4 levels (Ki vs SLEDAI, r = 0.607, p = 0.021; Ki vs C3, r = - 0.568, p = 0.034; Ki vs C4, r = - 0.661, p = 0.010). There were no significantly correlations between lung FDG uptake and pulmonary vascular haemodynamics and 6 min walking distance in both IPAH and SLE-PAH patients. CONCLUSIONS: Our data indicated that increased lung FDG uptake in SLE-PAH patients correlates with SLE disease activity (SLEDAI) and immune/inflammatory status (C3 and C4). FDG-PET imaging may be developed as a potential intrapulmonary disease activity marker in SLE-PAH patients.

Advances in Optical Coherence Tomography and Confocal Laser Endomicroscopy in Pulmonary Diseases.

Diagnosing and monitoring pulmonary diseases is highly dependent on imaging, physiological function tests and tissue sampling. Optical coherence tomography (OCT) and confocal laser endomicroscopy (CLE) are novel imaging techniques with near-microscopic resolution that can be easily and safely combined with conventional bronchoscopy. Disease-related pulmonary anatomical compartments can be visualized, real time, using these techniques. In obstructive lung diseases, airway wall layers and related structural remodelling can be identified and quantified. In malignant lung disease, normal and malignant areas of the central airways, lung parenchyma, lymph nodes and pleura can be discriminated. A growing number of interstitial lung diseases (ILDs) have been visualized using OCT or CLE. Several ILD-associated structural changes can be imaged: fibrosis, cellular infiltration, bronchi(ol)ectasis, cysts and microscopic honeycombing. Although not yet implemented in clinical practice, OCT and CLE have the potential to improve detection and monitoring pulmonary diseases and can contribute in unravelling the pathophysiology of disease and mechanism of action of novel treatments. Indeed, assessment of the airway wall layers with OCT might be helpful when evaluating treatments targeting airway remodelling. By visualizing individual malignant cells, CLE has the potential as a real-time lung cancer detection tool. In the future, both techniques could be combined with laser-enhanced fluorescent-labelled tracer detection. This review discusses the value of OCT and CLE in pulmonary medicine by summarizing the current evidence and elaborating on future perspectives.

Lung transplantation for pulmonary hypertension with giant pulmonary artery aneurysm.

BACKGROUND: Aneurysm of the main pulmonary artery trunk (PAA) is a rare but severe complicating factor in patients suffering from pulmonary arterial hypertension (PAH). Many centers consider PAA an indication for a heart-lung transplantation. We aimed to summarize our institutional experience with a lung-only strategy in this complex group of patients. METHODS: We performed a retrospective single-center analysis of patients with PAH and a severe PAA who underwent lung transplantation between January 1996 and November 2018. RESULTS: A total of 127 patients with PAH underwent lung transplantation during the study period. Seven patients presented with severe PAA (mean diameter, 70.4 mm). Donor lungs were procured together with the main pulmonary artery (PA). In the recipient, cardiopulmonary bypass with bicaval cannulation was established, and bilateral pneumonectomy together with resection of the entire PA trunk was performed. The right donor lung was implanted, and the attached PA trunk was pulled through behind the superior vena cava and ascending aorta. Anastomosis was performed just above the level of the pulmonary valve. Thereafter, the left lung was implanted by reconnecting the left PA to the main PA trunk. All but 1 patient, who died from sepsis on postoperative day 13, were successfully discharged. CONCLUSIONS: To the best of our knowledge, this is the largest published experience of patients with PAH and severe PAA who underwent lung transplantation. We show that these patients are eligible for double lung transplantation and do not require heart-lung transplantation.

Del soplo inocente a la hipertensión arterial pulmonar / From an innocent heart murmur to pulmonary arterial hypertension

Resumen Introducción: La detección de cardiopatías congénitas en la etapa neonatal a partir de un soplo cardiaco o cianosis no es efectiva. Las cardiopatías congénitas críticas, como el tronco arterioso común (TAC), causan la mayoría de las muertes neonatales por malformaciones congénitas. El tamizaje por oximetría de pulso en los recién nacidos detecta hasta el 70% de estas cardiopatías. El TAC presenta una alta mortalidad en el primer año de vida. Caso clínico: Se presenta el caso de un paciente de sexo femenino de 4 años de edad con soplo cardiaco, palpitaciones, disnea y cianosis perioral, con diagnóstico al nacimiento de soplo inocente. Se detectó TAC mediante una ecocardiografía. Las resistencias vasculares pulmonares fueron evaluadas por medio de cateterismo cardiaco derecho, con hallazgo de hipertensión arterial pulmonar y vasorreactividad pulmonar. Se realizó corrección quirúrgica. A la fecha, la hipertensión arterial pulmonar continúa presente, por lo que se implementó Bosentan® (Actelion, USA) como tratamiento a largo plazo. Conclusiones: En recién nacidos, el tamizaje por oximetría de pulso después de las 24 horas de vida es un método efectivo para el diagnóstico oportuno de cardiopatías congénitas críticas antes de los signos de colapso cardiovascular. Por ello, resulta una herramienta diagnóstica fundamental para reducir la morbimortalidad. Aunque la corrección quirúrgica de cardiopatías congénitas con hipertensión arterial pulmonar es factible en algunos pacientes, su manejo subsecuente es complejo e impacta de manera adversa en la calidad de vida.

Abstract Background: The detection of congenital heart disease in newborns, based on a heart murmur or cyanosis is not effective. Critical congenital heart diseases, such as truncus arteriosus (TA), cause most of neonatal deaths due to congenital malformations. The screening for pulse oximetry in newborns detects up to 70% of these heart diseases. TA presents high mortality in the first year of life. Case report: A 4-year-old female patient with a heart murmur, palpitations, dyspnea, and perioral cyanosis was diagnosed with an innocent heart murmur at birth. TA was detected by echocardiography. Pulmonary vascular resistances were evaluated through right cardiac catheterization, and pulmonary arterial hypertension and pulmonary vasoreactivity were diagnosed as well. Surgical correction was performed. Currently, pulmonary arterial hypertension persists, for which Bosentan® (Actelion, USA) has been implemented as a long-term treatment. Conclusions: In newborns, the pulse oximetry screening after 24 hours of life is an effective method for suitable diagnosis of critical congenital heart disease before the signs of cardiovascular collapse. Therefore, it has become an essential diagnostic tool to reduce morbidity and mortality. Although the surgical correction of congenital heart disease with pulmonary arterial hypertension is feasible in some patients, its subsequent management is complex and has an adverse impact on the quality of life.

Diverse cardiopulmonary diseases are associated with distinct xenon magnetic resonance imaging signatures.

BACKGROUND: As an increasing number of patients exhibit concomitant cardiac and pulmonary disease, limitations of standard diagnostic criteria are more frequently encountered. Here, we apply noninvasive 129Xe magnetic resonance imaging (MRI) and spectroscopy to identify patterns of regional gas transfer impairment and haemodynamics that are uniquely associated with chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), left heart failure (LHF) and pulmonary arterial hypertension (PAH). METHODS: Healthy volunteers (n=23) and patients with COPD (n=8), IPF (n=12), LHF (n=6) and PAH (n=10) underwent 129Xe gas transfer imaging and dynamic spectroscopy. For each patient, three-dimensional maps were generated to depict ventilation, barrier uptake (129Xe dissolved in interstitial tissue) and red blood cell (RBC) transfer (129Xe dissolved in RBCs). Dynamic 129Xe spectroscopy was used to quantify cardiogenic oscillations in the RBC signal amplitude and frequency shift. RESULTS: Compared with healthy volunteers, all patient groups exhibited decreased ventilation and RBC transfer (both p≤0.01). Patients with COPD demonstrated more ventilation and barrier defects compared with all other groups (both p≤0.02). In contrast, IPF patients demonstrated elevated barrier uptake compared with all other groups (p≤0.007), and increased RBC amplitude and shift oscillations compared with healthy volunteers (p=0.007 and p≤0.01, respectively). Patients with COPD and PAH both exhibited decreased RBC amplitude oscillations (p=0.02 and p=0.005, respectively) compared with healthy volunteers. LHF was distinguishable from PAH by enhanced RBC amplitude oscillations (p=0.01). CONCLUSION: COPD, IPF, LHF and PAH each exhibit unique 129Xe MRI and dynamic spectroscopy signatures. These metrics may help with diagnostic challenges in cardiopulmonary disease and increase understanding of regional lung function and haemodynamics at the alveolar-capillary level.