Curcumin regulates pulmonary extracellular matrix remodeling and mitochondrial function to attenuate pulmonary fibrosis by regulating the miR-29a-3p/DNMT3A axis.

Epigenetic regulation and mitochondrial dysfunction are essential to the progression of idiopathic pulmonary fibrosis (IPF). Curcumin (CCM) in inhibits the progression of pulmonary fibrosis by regulating the expression of specific miRNAs and pulmonary fibroblast mitochondrial function; however, the underlying mechanism is unclear. C57BL/6 mice were intratracheally injected with bleomycin (5 mg/kg) and treated with CCM (25 mg/kg body weight/3 times per week, intraperitoneal injection) for 28 days. Verhoeff-Van Gieson, Picro sirius red, and Masson's trichrome staining were used to examine the expression and distribution of collagen and elastic fibers in the lung tissue. Pulmonary fibrosis was determined using micro-computed tomography and transmission electron microscopy. Human pulmonary fibroblasts were transfected with miR-29a-3p, and RT-qPCR, immunostaining, and western blotting were performed to determine the expression of DNMT3A and extracellular matrix collagen-1 (COL1A1) and fibronectin-1 (FN1) levels. The expression of mitochondrial electron transport chain complex (MRC) and mitochondrial function were detected using western blotting and Seahorse XFp Technology. CCM in increased the expression of miR-29a-3p in the lung tissue and inhibited the DNMT3A to reduce the COL1A1 and FN1 levels leading to pulmonary extracellular matrix remodeling. In addition, CCM inhibited pulmonary fibroblasts MRC and mitochondrial function via the miR-29a-3p/DNMT3A pathway. CCM attenuates pulmonary fibrosis via the miR-29a-3p/DNMT3A axis to regulate extracellular matrix remodeling and mitochondrial function and may provide a new therapeutic intervention for preventing pulmonary fibrosis.

TIMECARD score: An easily operated prediction model of unfavorable neurological outcomes in out-of-hospital cardiac arrest patients with targeted temperature management.

BACKGROUND: Targeted temperature management (TTM) is recommended for comatose out-of-hospital cardiac arrest (OHCA) survivors. Several prediction models have been proposed; however, most of these tools require data conversion and complex calculations. Early and easy predictive model of neurological prognosis in OHCA survivors with TTM warrant investigation. MATERIALS AND METHODS: This multicenter retrospective cohort study enrolled 408 non-traumatic adult OHCA survivors with TTM from the TaIwan network of targeted temperature ManagEment for CARDiac arrest (TIMECARD) registry during January 2014 to June 2019. The primary outcome was unfavorable neurological outcome at discharge. The clinical variables associated with unfavorable neurological outcomes were identified and a risk prediction score-TIMECARD score was developed. The model was validated with data from National Taiwan University Hospital. RESULTS: There were 319 (78.2%) patients presented unfavorable neurological outcomes at hospital discharge. Eight independent variables, including malignancy, no bystander cardiopulmonary resuscitation (CPR), non-shockable rhythm, call-to-start CPR duration >5 min, CPR duration >20 min, sodium bicarbonate use during resuscitation, Glasgow Coma Scale motor score of 1 at return of spontaneous circulation, and no emergent coronary angiography, revealed a significant correlation with unfavorable neurological prognosis in TTM-treated OHCA survivors. The TIMECARD score was established and demonstrated good discriminatory performance in the development cohort (area under the receiver operating characteristic curve [AUC] = 0.855) and validation cohorts (AUC = 0.918 and 0.877, respectively). CONCLUSION: In emergency settings, the TIMECARD score is a practical and simple-to-calculate tool for predicting neurological prognosis in OHCA survivors, and may help determine whether to initiate TTM in indicated patients.

Evolutionary changes in thrombus features on computed tomography: An effective approach for identifying subacute pulmonary embolism.

OBJECTIVE: Thrombus features on computed tomography (CT) play a key role in distinguishing between acute and chronic pulmonary embolisms (PEs). However, the thrombus features of subacute PE are largely unknown. METHODS: This retrospective study included 358 patients (age, 65 ± 16 years; percentage of men, 38%) diagnosed with PE from 2008 to 2019. The patients were divided into a study group and a verification group. Thrombus features that changed over time were determined in the study group according to the time of PE occurrence. Next, we determined the thrombus features of subacute PE and verified them in the verification group. Finally, we compared clinical deterioration and the 1-month mortality rate between the patients with acute and subacute PEs. RESULTS: The main feature of eccentric thrombi that changed over time was the angle with the arterial wall, whereas those of centric thrombi were recanalization and heterogeneity. Taken together, the features of subacute PE were determined to be an obtuse angle with the arterial wall, recanalization, and heterogeneity. The accuracy of these features in identifying subacute PE was 94% during verification. Between the patients with acute and subacute PEs, there was no significant difference in clinical deterioration (19% vs 14%; P = .32) or the 1-month mortality rate (15% vs 8%; P = .11). With multivariate analysis, subacute events were also not associated with clinical deterioration (P = .8) or the 1-month mortality rate (P = .11). CONCLUSIONS: We determined the time trend of thrombus features on CT in patients with PE and found that these features can improve the identification of subacute events. Patients with acute and subacute PEs do not have different risks of clinical deterioration and 1-month mortality.

ISHLT consensus statement: Perioperative management of patients with pulmonary hypertension and right heart failure undergoing surgery.

Pulmonary hypertension (PH) is a risk factor for morbidity and mortality in patients undergoing surgery and anesthesia. This document represents the first international consensus statement for the perioperative management of patients with pulmonary hypertension and right heart failure. It includes recommendations for managing patients with PH being considered for surgery, including preoperative risk assessment, planning, intra- and postoperative monitoring and management strategies that can improve outcomes in this vulnerable population. This is a comprehensive document that includes common perioperative patient populations and surgical procedures with unique considerations.

Prothymosin α Gene Transfer Modulates Myocardial Remodeling after Ischemia-Reperfusion Injury.

Background: Prothymosin α (ProT), a polypeptide, attenuates inflammation and inhibits transforming growth factor (TGF)-ß signaling in pulmonary tissues. We investigated the potential role of ProT in myocardial ischemia-reperfusion (MyoIR) injury using ProT cDNA transfer. Methods: Serum ProT levels were investigated in cardiogenic shock patients with MyoIR (n = 9). In addition, the myocardium of Sprague-Dawley rats (n = 52) was subjected to 25 min of ischemia followed by an injection of adenoviral vectors (2 × 109 plaque-forming units) carrying ProT or the luciferase gene, 10 min before reperfusion. Echocardiography, serum ProT, and biochemical analyses of organ functions were performed before euthanasia, 14 days after treatment. Immunohistochemistry and immunoblotting of the myocardial tissue were also performed. Results: Serum ProT levels were transiently elevated in the rats and patients early after MyoIR, which was reduced to baseline levels in control rats and patients. ProT gene transfer persistently mobilized ProT serum levels, reduced dilatation, attenuated fibrotic changes, and preserved the left ventricular ejection fraction after MyoIR. Tissue thrombospondin-1 level was abundant, and matrix metalloproteinase-2, collagen I, and collagen IV levels were decreased in the treatment group. While TGF-ß protein level remained stable, ProT transduction mobilized Smad7, which counteracted TGF-ß. ProT reduced tissue microRNA-223 expression, inhibited the associated interleukin-1ß, and preserved RAS p21 protein activator 1 protein abundance. Conclusions: An increase in transient serum ProT levels could be a protective response in the acute stage of MyoIR. ProT gene transfer further preserved ventricular morphology and function through anti-inflammatory and anti-fibrotic effects in the subacute stage after injury.

Dynamic Changes in miR-21 Regulate Right Ventricular Dysfunction in Congenital Heart Disease-Related Pulmonary Arterial Hypertension.

Right ventricular (RV) failure is a major cause of mortality in pulmonary arterial hypertension (PAH), but its mechanism remains largely unknown. MicroRNA-21 (miR-21) is involved in flow-mediated stress in the vasculature, but its effects on RV remodeling require investigations. Herein, we aim to study the mechanism of miR-21 in the early (compensated) and late (decompensated) phases of PAH-induced RV dysfunction. Using aorto-venous fistula (AVS) surgery, we established a rat model of PAH. To mimic the microenvironment of PAH, we treated cardiomyocytes with flow-mediated shear stress in 6 dyne for 3 and 8 h. To evaluate whether miR-21 could be a biomarker, we prospectively collected the sera of patients with congenital heart disease- (CHD) related PAH. Additionally, clinical, echocardiographic and right heart catheterization information was collected. The primary endpoint was hospitalization for decompensated heart failure (HF). It is of note that, despite an initial increase in miR-21 expression in hypertrophic RV post AVS, miR-21 expression decreased with RV dysfunction thereafter. Likewise, the activation of miR-21 in cardiomyocytes under shear stress at 3 h was downregulated at 6 h. The downregulated miR-21 at the late phase was associated with increased apoptosis in cardiomyocytes while miR-21 mimic rescued it. Among 76 CHD-induced PAH patients, 19 who were hospitalized for heart failure represented with a significantly lower expression of circulating miR-21. Collectively, our study revealed that the upregulation of miR-21 in the early phase (RV hypertrophy) and downregulation in the late phase (RV dysfunction) under PAH triggered a biphasic regulation of cardiac remodeling and cardiomyocyte apoptosis.

Transplantation of viable mitochondria improves right ventricular performance and pulmonary artery remodeling in rats with pulmonary arterial hypertension.

OBJECTIVE: Because mitochondrial dysfunction is a key factor in the progression of pulmonary hypertension, this study tested the hypothesis that transplantation of exogenous viable mitochondria can reverse pulmonary artery remodeling and restore right ventricular performance in pulmonary hypertension. METHODS: Pulmonary hypertension was induced by parenteral injection of monocrotaline (60 mg/kg) and creation of a left-to-right shunt aortocaval fistula in rats. Three weeks after creation of fistula, the animals were randomly assigned to receive intravenous delivery of placebo solution or allogeneic mitochondria once weekly for 3 consecutive weeks. Mitochondria (100 µg) were isolated from the freshly harvested soleus muscles of naïve rats. Transthoracic echocardiography was performed at 3 weeks after mitochondrial delivery. RESULTS: Ex vivo heart-lung block images acquired by an IVIS Spectrum (PerkinElmer, Waltham, Mass) imaging system confirmed the enhancement of MitoTracker (Invitrogen, Carlsbad, Calif) fluorescence in the pulmonary arteries. Mitochondria transplantation significantly increased lung tissue adenosine triphosphate concentrations and improved right ventricular performance, as evidenced by a reduction in serum levels of B-type natriuretic peptide and ventricular diameter. Right ventricular mass and wall thickness were restored in the mitochondrial group. In the pulmonary arteries of rats that received mitochondrial treatment, vascular smooth muscle cells expressed higher levels of α-smooth muscle actin and smooth muscle myosin heavy chain II, indicating the maintenance of the nonproliferative, contractile phenotype. The hyper-reactivity of isolated pulmonary arteries to α-adrenergic stimulation was also attenuated after mitochondrial transplantation. CONCLUSIONS: Transplantation of viable mitochondria can restore the contractile phenotype and vasoreactivity of the pulmonary artery, thereby reducing the afterload and right ventricular remodeling in rats with established pulmonary hypertension. The improvement in overall right ventricular performance suggests that mitochondrial transplantation can be a revolutionary clinical therapeutic option for the management of pulmonary hypertension.

A Case Report of Posttransplant Lymphoproliferative Disorder After AstraZeneca Coronavirus Disease 2019 Vaccine in a Heart Transplant Recipient.

We report a case of a heart transplant recipient who presented with a rapidly growing Epstein-Barr virus (EBV)-positive, diffuse large B-cell lymphoma 7 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine. Because of the atypical radiologic presentation, the initial tentative diagnosis was a mediastinal abscess. This observation indicates a potential risk of EBV reactivation after coronavirus disease 2019 (COVID-19) vaccination, which might lead to or aggravate the presentation of posttransplant lymphoproliferative disorder in transplantation patients. Transplant surgeons should be aware of the potential immunomodulatory effects of the COVID-19 vaccination.

Endocardial Endothelial Dysfunction and Unknown Polymorphic Composite Accumulation in Heart Failure.

The accumulation of unknown polymorphic composites in the endocardium damages the endocardial endothelium (EE). However, the composition and role of unknown polymorphic composites in heart failure (HF) progression remain unclear. Here, we aimed to explore composite deposition during endocardium damage and HF progression. Adult male Sprague-Dawley rats were divided into two HF groups-angiotensin II-induced HF and left anterior descending artery ligation-induced HF. Heart tissues from patients who had undergone coronary artery bypass graft surgery (non-HF) and those with dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) were collected. EE damage, polymorphic unknown composite accumulation, and elements in deposits were examined. HF progression reduced the expression of CD31 in the endocardium, impaired endocardial integrity, and exposed the myofibrils and mitochondria. The damaged endocardial surface showed the accumulation of unknown polymorphic composites. In the animal HF model, especially HF caused by myocardial infarction, the weight and atomic percentages of O, Na, and N in the deposited composites were significantly higher than those of the other groups. The deposited composites in the human HF heart section (DCM) had a significantly higher percentage of Na and S than the other groups, whereas the percentage of C and Na in the DCM and ICM groups was significantly higher than those of the control group. HF causes widespread EE dysfunction, and EndMT was accompanied by polymorphic composites of different shapes and elemental compositions, which further damage and deteriorate heart function.

Incidence of chronic thromboembolic pulmonary hypertension in Taiwan.

BACKGROUND: The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is complex, and the modality of treatment is surgery and targeted medication. Patients with CTEPH could have a poor prognosis if their diagnosis or treatment is delayed. The incidence of CTEPH and its clinical features are largely unknown in Taiwan, even among other Asian populations. In this study, we aimed to investigate the geodemographics of CTEPH in Taiwan and describe the practical management and treatment outcomes in patients with CTEPH. METHODS: This study retrospectively enrolled patients in the Taiwan cohort - Registry of CTEPH. The study was conducted over 2 years inclusive of follow-up. The enrolment criteria depended on the current global guideline. RESULTS: From January 2018 to March 2020, 107 CTEPH patients enrolled in the Taiwan registry. All patients received right heart catheterisation examinations. The overall median age was 61.4 ± 16.5 years, and the cohort was dominated by female patients (75/107). Risk factors included pulmonary embolism (81.3%), deep vein thrombosis (22.4%), and previous major surgery (20.6%). Twenty-one (19.6%) patients underwent pulmonary endarterectomy operation alone, and 38 (35.5%) patients underwent balloon pulmonary angioplasty alone. CONCLUSION: To our knowledge, this is the first national cohort study that demonstrated the raw CTEPH incidence in Taiwan. It also showed the CTEPH incidence between male and female patients in the Asian population was different from the Caucasian population.

Management of Venous Thromboembolisms: Part II. The Consensus for Pulmonary Embolism and Updates.

Pulmonary embolism (PE) is a potential life-threatening condition and risk-adapted diagnostic and therapeutic management conveys a favorable outcome. For patients at high risk for early complications and mortality, prompt exclusion or confirmation of PE by imaging is the key step to initiate and facilitate reperfusion treatment. Among patients with hemodynamic instability, systemic thrombolysis improves survival, whereas surgical embolectomy or percutaneous intervention are alternatives in experienced hands in scenarios where systemic thrombolysis is not the best preferred thromboreduction measure. For patients with suspected PE who are not at high risk for early complications and mortality, the organized approach using a structured evaluation system to assess the pretest probability, the age-adjusted D-dimer cut-offs, the appropriate selection of imaging tools, and proper interpretation of imaging results is important when deciding the allocation of treatment strategies. Patients with PE requires anticoagulation treatment. In patients with cancer and thrombosis, low-molecular-weight heparin (LMWH) used to be the standard regimen. Recently, three factor Xa inhibitors collectively show that non-vitamin K oral anticoagulants (NOACs) are as effective as LMWH in four randomized clinical trials. Therefore, NOACs are suitable and preferred in most conditions. Finally, chronic thromboembolic pulmonary hypertension is the most disabling long-term complication of PE. Because of its low incidence, the extra caution should be given when managing patients with PE.

ProT-α gene transfer attenuates cardiopulmonary remedying and mortality in a flow-induced pulmonary hypertension rat model.

BACKGROUND: ProT is a cell survival gene, which modulates oxidative stress and transforming growth factor (TGF)-ß signaling. We hypothesized that the delivery of the ProT cDNA gene in rats could protect against right heart dysfunction secondary to pulmonary hypertension (PH) induced by left-to-right shunt. METHODS: A 2-hit rat model of flow-induced PH was used, and a single intravenous injection of adenoviral vectors (2 billion plaque-forming unit) carrying ProT or Luc gene was administered. The animals were euthanized 21 days after gene delivery to assess cardiopulmonary function, serum biochemistry, pulmonary artery (PA), and vasomotor reactivity. Immunohistology and immunoblotting of PA tissues were also performed. RESULTS: ProT transduction significantly reduced PA pressure, right ventricle muscle mass, and wall stress, thereby improving the overall survival of the treated rat. Increased production of ProT through gene therapy preserved both the smooth muscle myosin heavy chain-II and α-smooth muscle actin while counteracting the abundance of TGF-ß in PA. Protein abundances of phosphorylated p47-phox, heme oxygenase-1, caspase-3, inducible nitric oxide synthase, cyclo-oxygenase 2, and monocyte chemoattractant protein-1 in PA tissues were reduced. ProT also preserved microRNA-223, thereby suppressing the abundance of PARP-1, which is independent of hypoxia-inducible factor-1α signaling. CONCLUSIONS: ProT gene transduction improved PA function by reducing oxidative stress, attenuating inflammation, and preserving the contractile phenotype of vascular smooth muscle cells. The modification of microRNA-223-associated downstream signaling through ProT transduction may play an important role in mitigating cardiopulmonary remodeling in flow-induced PH.

Pulmonary thromboembolism with computed tomography defined chronic thrombus is associated with higher mortality.

With the advancement of computed tomography pulmonary angiography, differentiating between acute and chronic thrombus in pulmonary embolism has become more feasible. However, whether pulmonary embolism with chronic thrombus contributes to a higher mortality than pulmonary embolism with acute thrombus remains undetermined. Additionally, the clinical features of patients with chronic thrombus are largely unknown. Herein, we aimed to investigate the incidence and outcomes of patients with pulmonary embolism and chronic thrombus. This retrospective study included patients with pulmonary embolism from 2008 to 2016 at National Cheng Kung University Hospital. After excluding patients with tumor emboli or other etiologies and a lack of computed tomography images, we identified 205 patients with acute thrombus and 58 patients with chronic thrombus. Patients with chronic thrombus initially presented mainly with dyspnea, and the etiology was not related to recent surgery. Patients with chronic thrombus had a significantly higher incidence of elevated right ventricular systolic pressure detected by echocardiography and a higher incidence of subsequent events due to residual pulmonary embolism. Despite no differences in clinically recurrent pulmonary embolism, patients with chronic thrombus presented with a higher risk of all-cause and pulmonary embolism-related mortality than patients with acute thrombus. Chronic thrombus (hazard ratio: 2.03, p = 0.03), simplified pulmonary embolism severity index, anticoagulant use, and body mass index were the independent factors for all-cause mortality. Our findings suggest that using computed tomography pulmonary angiography for identifying patients with pulmonary embolism and chronic thrombus, which was associated with a higher risk of mortality, is pivotal for early intervention in addition to anticoagulant use.

Right ventricular reserve post mitral valve repair is associated with heart failure hospitalization.

Right ventricular impairment is a predictor of cardiovascular outcomes in patients with degenerative mitral regurgitation. However, the time course of right ventricular functional changes post-surgical mitral valve repair remains largely unknown. Herein, using right ventricular-focused echocardiography, we aimed to investigate right ventricular reserve and its impact on hospitalization for heart failure after mitral valve repair. In this prospective study, we enrolled 108 patients scheduled to undergo surgical repair of degenerative mitral regurgitation. Echocardiography, including right ventricular strain analysis, was performed prior to, and one month and six months post mitral valve repair. Right ventricular strain that improved one month post-surgery was defined as reserved right ventricular. In addition, any cardiovascular outcomes comprising heart failure that required admission were recorded. The median follow-up duration is 31 months. Despite a significant improvement in mitral valve regurgitant volume post-operatively, left ventricular ejection fraction (LVEF) at six months was similar to LVEF at baseline. There was a transient decrease in LV longitudinal strain at one month that was recovered six months post mitral valve repair. Regarding the right ventricular, in contrast with conventional right ventricular parameters, including right ventricular tissue Doppler S', fractional area change and tricuspid annular plane systolic excursion (TAPSE), only resolution of right ventricular strain at one month predicted the subsequent myocardial recovery. Furthermore, patients with reserved right ventricular had a lower risk of hospitalization for heart failure compared to those with non-reserved right ventricular. Collectively, the early resolution of right ventricular strain is associated with the improvement in right ventricular function (measured by TAPSE) and in heart failure hospitalization in patients who had undergone surgical mitral valve repair for degenerative mitral regurgitation.

Right ventricular dysfunction is associated with the development of chronic thromboembolic pulmonary hypertension but not with mortality post-acute pulmonary embolism.

Chronic thromboembolic pulmonary hypertension (CTEPH), a late complication of pulmonary embolism (PE), is associated with high mortality. However, whether the right ventricular (RV) echocardiographic parameters can predict - in the short- and long-term - the development of CTEPH and mortality after PE remains unknown. Herein, we aim to investigate the incidence of CTEPH after acute PE and to evaluate the risk factors of CTEPH. In this retrospective cohort, patients with PE were followed for 10 years for the onset of CTEPH. The screening was initially conducted through echocardiography and confirmed by right heart catheterization. Also, transient and permanent risk factors were identified. Among 358 patients with PE, 8 patients (4%) were subsequently diagnosed with CTEPH at a median time of 36 months and 47 died during the follow-up period. Notably, both short- and long-term RV dilatation, hypertrophy, and increased pulmonary pressure increased the incidence of CTEPH. However, RV echocardiographic parameters failed to differentiate survivors from non-survivors. Instead, malignancy, respiratory, or chronic heart failure was strongly associated with post PE mortality in the multivariable analysis. According to our findings, post PE screening of CTEPH may facilitate early diagnosis and intervention for patients at high risk of developing CTEPH. Also, RV echocardiographic parameters are associated with subsequent CTEPH, but mortality is mainly dependent on underlying comorbidities.

Exendin-4 improves cardiovascular function and survival in flow-induced pulmonary hypertension.

OBJECTIVES: Systemic left-to-right shunting causes pulmonary arteriopathy, leading to progressive cardiopulmonary failure and a poor prognosis. In this study, we examined the extraglycemic effect of a synthetic glucagon-like peptide, exendin-4, on pulmonary arteriopathy regression and cardiopulmonary function in nondiabetic rats. METHODS: Pulmonary hypertension (PH) was induced by monocrotaline (60 mg/kg, subcutaneous) injection followed by the creation of an aortocaval fistula. After 4 weeks, exendin-4 (1 µg/kg/day) was administered intraperitoneally for 3 consecutive weeks, followed by an assessment of cardiopulmonary function, pulmonary artery vasoreactivity, tissue and blood biochemistry, and lung histology. RESULTS: Exendin-4 significantly reduced right ventricle mass and pulmonary artery pressure, which improved right ventricle function and the survival rate in rats with PH. Tissue and blood interleukin-1ß levels decreased, whereas pulmonary artery cyclic adenosine monophosphate levels were restored by exendin-4. Smooth muscle-myosin heavy chain-II and α-smooth muscle actin protein levels increased in the pulmonary arteries of exendin-4-treated rats. Histology showed that exendin-4 decreased the main and intra-acinar pulmonary artery medial thickness. CONCLUSIONS: Exendin-4 treatment improved pulmonary artery function in flow-induced PH via its direct vasoactive properties, anti-inflammatory effects, and vascular smooth muscle cell phenotypic modulation. Mitigation of pulmonary arteriopathy further potentiated right ventricle performance and reduced overall mortality. These responses were associated with suppressed expression and activity of interleukin-1ß and its downstream signaling molecules. Glucagon-like peptide analogs may possess pleiotropic therapeutic potential in flow-induced PH.

Bridge-to-recovery strategy using extracorporeal membrane oxygenation for critical pulmonary hypertension complicated with cardiogenic shock.

OBJECTIVES: Studies on mechanical-medical bridging for decompensated pulmonary hypertension (PH) are limited. We analysed the outcomes for critical PH patients who underwent extracorporeal membrane oxygenation (ECMO) support using a bridge-to-recovery (BTR) strategy. This study aimed to identify prognostic factors of BTR and evaluate the outcomes of survivors. METHODS: Between 2009 and 2012, 6 patients who received veno-arterial ECMO due to decompensated PH with cardiogenic shock were retrospectively reviewed. All of the patients were managed with an aggressive titration of PH therapies and the optimization of right ventricular (RV) function to wean them off of ECMO. Three of the patients survived to discharge, and the others suffered in-hospital mortality. The differences between their baseline characteristics, ECMO set-up, haemodynamic change and complications were analysed. RESULTS: The average age was 46.67 ± 14.07 years, with a male-to-female ratio of 1:2. The non-survival group exhibited a higher baseline systolic pulmonary artery pressure (127.67 ± 25.81 vs 67.67 ± 24.83 mmHg, P = 0.044) than the survival group before ECMO. All of the non-survivors underwent cardiopulmonary-cerebral resuscitation prior to ECMO implantation (100 vs 0%, P = 0.100). The survivors tended to have received suboptimal PH therapies before ECMO and had more readily correctable predisposing factors of right ventricular failure. The non-survivors required a longer duration of ECMO and suffered more end-organ failure or sepsis, although those differences were not statistically significant. Pneumonia developed in 3 of the survivors and caused late mortality in 2 after discharge. CONCLUSIONS: ECMO provides a therapeutic window for the medical stabilization of critically decompensated PH patients. Prompt ECMO intervention before haemodynamic collapse and careful patient selection are critical for successful BTR outcomes.

Rosuvastatin improves vascular function of arteriovenous fistula in a diabetic rat model.

OBJECTIVE: This study investigates the pathogenesis of arteriovenous (AV) fistula failure in patients with diabetes mellitus (DM) and tests the vascular protective effect of rosuvastatin on the fistulous communication of diabetic rats. METHODS: DM was induced in rats by a single injection of streptozotocin. One week later, a fistula was created in the descending aorta and the adjacent inferior vena cava (aortocaval [AC] fistula). Rats were then randomly assigned to receive placebo or rosuvastatin (15 mg/kg/d) in chow for 2 weeks. Blood flow in the aortic segments of the fistula was measured. Circulating CD34+/KDR+ endothelial progenitor cells (EPCs) were determined 2 weeks after creation of the AC fistulas using flow cytometry. Vascular function of the AC fistulas was assessed by isometric force testing. The expression of proinflammatory genes and generation of superoxide anions in the fistulas were examined. RESULTS: The number of EPCs was reduced in diabetic rats, and rosuvastatin significantly increased the number of circulating EPCs. Reduced blood flow and impaired endothelium-dependent relaxation in the AC fistula of animals with diabetes was significantly potentiated after treatment with rosuvastatin. Rosuvastatin also attenuated the expression of inducible nitric oxide synthase and nicotinamide adenine dinucleotide phosphate oxidase and generation of superoxide anions in the fistula tissues isolated from diabetic rats. CONCLUSIONS: We provide the first evidence demonstrating that rosuvastatin improves blood flow and endothelial function of AC fistulas in rats with DM by attenuating the activity of proinflammatory genes and generation of superoxide anions in the remodeled vasculature. CLINICAL RELEVANCE: Arteriovenous (AV) fistula is the most common vascular access for hemodialysis in patients with end-stage renal disease. Studies have shown that blood flow in the AV fistula is significantly reduced in patients with diabetes and the period for maturation of an AV fistula is longer in these patients. The underlying mechanisms of AV fistula failure in diabetes are still poorly understood and there are limited therapeutic approaches that can increase the lifespan of these fistulas. The present study demonstrates that oral administration rosuvastatin improves blood flow and endothelial function of AC fistulas in rats with diabetes, which results from attenuating the activity of proinflammatory genes in the remodeled vasculature, thereby reducing the generation of tissue superoxide anions. Our results may thus enhance our ability to prevent and manage vascular access failure in patients with diabetes with chronic renal disease.

Chylous ascites and chylothorax: an unusual manifestation of cardiac amyloidosis.

Restrictive cardiomyopathy is an extremely rare cause of massive chylous ascites and chylothorax. We report a 56-year-old man patient who presented with chylous ascites and bilateral chylothorax; 12-lead electrocardiography and echocardiography revealed restrictive cardiomyopathy. Endomyocardial biopsy disclosed amyloidosis.

Judicious use of transthoracic echocardiography in infective endocarditis screening.

BACKGROUND: Patients with a very low probability of infective endocarditis (IE) do not benefit from transthoracic echocardiography (TTE). Because the term 'very low probability' has not yet been defined, the present prospective study sought to identify the population with a 'very low probability'. METHODS: TTE was performed between July 2005 and October 2006 in consecutive patients clinically suspected of having IE. Clinical parameters suggestive of IE and presence of infectious focus were recorded. RESULTS: Twenty-four (15.5%) of 155 patients studied had positive findings on TTE. Significant positive predictors were embolic events, intravenous drug use, the presence of a prosthetic valve, positive blood cultures and immunological phenomena. The significant negative predictor was confirmed infection sites other than endocardium. Sixty-three (40.6%) of 155 patients without positive predictors were found to have no vegetation. Thus, the collective absence of these predictors indicated a zero probability of TTE showing evidence of IE. A significant negative predictor was a definite etiology of infection other than IE. Only one in 76 patients was diagnosed with both IE and infection at another site. CONCLUSIONS: The absence of positive predictors or the presence of a negative predictor indicate a near-zero probability of IE being detected by TTE. Use of clinical parameters may avoid up to 41% of unnecessary TTE examinations, increasing the likelihood that such a diagnosis will be correct.