Calcium channel blockers in patients with pulmonary arterial hypertension receiving PAH-specific treatment.

BACKGROUND: Calcium channel blockers (CCB) are the first effective therapy for vasoreactive patients with idiopathic pulmonary arterial hypertension (IPAH). However, the advent of modern PAH-specific drugs may undermine the role of vasoreactivity tests and CCB treatment. We aimed to clarify the effect of acute vasoreactivity testing and CCB on patients with IPAH receiving PAH-specific treatment. METHODS: We retrospectively investigated consecutive patients with IPAH (n = 136) diagnosed between 2000 and 2020 and collected data from patients who underwent acute vasoreactivity testing using inhaled nitric oxide (NO). The effects of vasoreactivity testing and CCB therapy were reviewed. Long-term survival was analysed using the Kaplan-Meier method. RESULTS: Acute vasoreactivity testing was performed in 49% of patients with IPAH (n = 67), including 23 patients (34%) receiving PAH-specific therapy without vasoreactivity testing. Eight patients (12%), including three patients (4.4%) receiving PAH-specific therapy, presented acute responses at vasoreactivity testing. They received high-dose CCB therapy (CCB monotherapy for five patients [7.5%] and CCB therapy and PAH-specific therapy for three patients [4.4%]). They presented a significant improvement in clinical parameters and near-normalisation of haemodynamics (mean pulmonary arterial pressure decreased from 46 [interquartile range: 40-49] to 19.5 [interquartile range: 18-23] mmHg [P < .001] at 1-year follow-up). All eight vasoreactive responders receiving CCB therapy showed better long-term survival than non-responders treated with PAH-specific therapy (P < .001). CONCLUSIONS: CCB therapy benefited patients with IPAH who showed acute response to vasoreactivity testing using inhaled NO, even when receiving modern PAH-specific therapy. Acute vasoreactive responders may benefit more from CCB than from PAH-specific therapy.

IL-6/gp130 signaling in CD4+ T cells drives the pathogenesis of pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is characterized by stenosis and occlusions of small pulmonary arteries, leading to elevated pulmonary arterial pressure and right heart failure. Although accumulating evidence shows the importance of interleukin (IL)-6 in the pathogenesis of PAH, the target cells of IL-6 are poorly understood. Using mice harboring the floxed allele of gp130, a subunit of the IL-6 receptor, we found substantial Cre recombination in all hematopoietic cell lineages from the primitive hematopoietic stem cell level in SM22α-Cre mice. We also revealed that a CD4+ cell-specific gp130 deletion ameliorated the phenotype of hypoxia-induced pulmonary hypertension in mice. Disruption of IL-6 signaling via deletion of gp130 in CD4+ T cells inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) and suppressed the hypoxia-induced increase in T helper 17 cells. To further examine the role of IL-6/gp130 signaling in more severe PH models, we developed Il6 knockout (KO) rats using the CRISPR/Cas9 system and showed that IL-6 deficiency could improve the pathophysiology in hypoxia-, monocrotaline-, and Sugen5416/hypoxia (SuHx)-induced rat PH models. Phosphorylation of STAT3 in CD4+ cells was also observed around the vascular lesions in the lungs of the SuHx rat model, but not in Il6 KO rats. Blockade of IL-6 signaling had an additive effect on conventional PAH therapeutics, such as endothelin receptor antagonist (macitentan) and soluble guanylyl cyclase stimulator (BAY41-2272). These findings suggest that IL-6/gp130 signaling in CD4+ cells plays a critical role in the pathogenesis of PAH.

Recurrent pulmonary hypertension after balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: Balloon pulmonary angioplasty improves the hemodynamics of patients with inoperable chronic thromboembolic pulmonary hypertension; however, the clinical impact of recurrent pulmonary hypertension after balloon pulmonary angioplasty remains unclear. METHODS: We retrospectively reviewed 262 consecutive patients with chronic thromboembolic pulmonary hypertension who underwent balloon pulmonary angioplasty between July 2009 and December 2020; 158 (65 ± 12 years; males, 20%; median follow-up period, 45 [26, 66] months) with follow-up right heart catheterization and no residual pulmonary hypertension were included. Recurrent pulmonary hypertension was defined as mean pulmonary arterial pressure <25 mm Hg at the first evaluation after balloon pulmonary angioplasty and ≥25 mm Hg at follow-up evaluation requiring additional treatment with balloon pulmonary angioplasty or pulmonary vasodilators. RESULTS: Recurrent pulmonary hypertension was observed in 11 patients; the state occupation probability of recurrence at 5 years was 9.0% (95% confidence interval: 5.0%-18.9%). Only 1 case (0.6%) of recurrent pulmonary hypertension showed vascular restenosis and reocclusion of previously treated lesions, with more significant hemodynamic and exercise capacity deterioration than the other cases. Additional treatments for recurrent pulmonary hypertension (balloon pulmonary angioplasty in 9 patients, pulmonary vasodilators in 4 patients) improved the mean pulmonary arterial pressure from 27 [26, 29] to 22 [19, 23] mm Hg (p < 0.01). Recurrence had a low probability of transitioning to death in an illness-death model. No specific risk factors for recurrent pulmonary hypertension were identified. CONCLUSIONS: Symptomatic recurrent pulmonary hypertension due to vascular restenosis or reocclusion after balloon pulmonary angioplasty was extremely rare. Most cases of recurrent pulmonary hypertension were mild, did not worsen clinically, and had favorable prognoses.

Gut dysbiosis is associated with aortic aneurysm formation and progression in Takayasu arteritis.

BACKGROUND: Takayasu arteritis (TAK) is an autoimmune large vessel vasculitis that affects the aorta and its major branches, eventually leading to the development of aortic aneurysm and vascular stenosis or occlusion. This retrospective and prospective study aimed to investigate whether the gut dysbiosis exists in patients with TAK and to identify specific gut microorganisms related to aortic aneurysm formation/progression in TAK. METHODS: We analysed the faecal microbiome of 76 patients with TAK and 56 healthy controls (HCs) using 16S ribosomal RNA sequencing. We examined the relationship between the composition of the gut microbiota and clinical parameters. RESULTS: The patients with TAK showed an altered gut microbiota with a higher abundance of oral-derived bacteria, such as Streptococcus and Campylobacter, regardless of the disease activity, than HCs. This increase was significantly associated with the administration of a proton pump inhibitor used for preventing gastric ulcers in patients treated with aspirin and glucocorticoids. Among patients taking a proton pump inhibitor, Campylobacter was more frequently detected in those who underwent vascular surgeries and endovascular therapy for aortic dilatation than in those who did not. Among the genus of Campylobacter, Campylobacter gracilis in the gut microbiome was significantly associated with clinical events related to aortic aneurysm formation/worsening in patients with TAK. In a prospective analysis, patients with a gut microbiome positive for Campylobacter were significantly more likely to require interventions for aortic dilatation than those who were negative for Campylobacter. Furthermore, patients with TAK who were positive for C. gracilis by polymerase chain reaction showed a tendency to have severe aortic aneurysms. CONCLUSIONS: A specific increase in oral-derived Campylobacter in the gut may be a novel predictor of aortic aneurysm formation/progression in patients with TAK.

Three Cases of Unprovoked Venous Thromboembolism with Prothrombin p.Arg596Gln Variant and a Literature Review of Antithrombin Resistance.

Antithrombin resistance (ATR) is a newly identified strong genetic predisposition to venous thromboembolism (VTE) caused by genetic variations in prothrombin with substitutions of Arg at position 596 with either Leu, Gln, or Trp. In the present report, we identified a missense variant p.Arg596Gln in 3 patients from 2 families with unprovoked VTE who each experienced their first VTE event at 19, 67, and 19 years old. The three patients did not show any positive markers for thrombophilia on routine testing, suggesting that patients with unprovoked VTE who have negative findings on thrombophilia tests may carry a prothrombin variant with ATR.

Regnase-1 Prevents Pulmonary Arterial Hypertension Through mRNA Degradation of Interleukin-6 and Platelet-Derived Growth Factor in Alveolar Macrophages.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a type of pulmonary hypertension (PH) characterized by obliterative pulmonary vascular remodeling, resulting in right-sided heart failure. Although the pathogenesis of PAH is not fully understood, inflammatory responses and cytokines have been shown to be associated with PAH, in particular, with connective tissue disease-PAH. In this sense, Regnase-1, an RNase that regulates mRNAs encoding genes related to immune reactions, was investigated in relation to the pathogenesis of PH. METHODS: We first examined the expression levels of ZC3H12A (encoding Regnase-1) in peripheral blood mononuclear cells from patients with PH classified under various types of PH, searching for an association between the ZC3H12A expression and clinical features. We then generated mice lacking Regnase-1 in myeloid cells, including alveolar macrophages, and examined right ventricular systolic pressures and histological changes in the lung. We further performed a comprehensive analysis of the transcriptome of alveolar macrophages and pulmonary arteries to identify genes regulated by Regnase-1 in alveolar macrophages. RESULTS: ZC3H12A expression in peripheral blood mononuclear cells was inversely correlated with the prognosis and severity of disease in patients with PH, in particular, in connective tissue disease-PAH. The critical role of Regnase-1 in controlling PAH was also reinforced by the analysis of mice lacking Regnase-1 in alveolar macrophages. These mice spontaneously developed severe PAH, characterized by the elevated right ventricular systolic pressures and irreversible pulmonary vascular remodeling, which recapitulated the pathology of patients with PAH. Transcriptomic analysis of alveolar macrophages and pulmonary arteries of these PAH mice revealed that Il6, Il1b, and Pdgfa/b are potential targets of Regnase-1 in alveolar macrophages in the regulation of PAH. The inhibition of IL-6 (interleukin-6) by an anti-IL-6 receptor antibody or platelet-derived growth factor by imatinib but not IL-1ß (interleukin-1ß) by anakinra, ameliorated the pathogenesis of PAH. CONCLUSIONS: Regnase-1 maintains lung innate immune homeostasis through the control of IL-6 and platelet-derived growth factor in alveolar macrophages, thereby suppressing the development of PAH in mice. Furthermore, the decreased expression of Regnase-1 in various types of PH implies its involvement in PH pathogenesis and may serve as a disease biomarker, and a therapeutic target for PH as well.

Prognostic impact of follow-up pulmonary vascular resistance in pulmonary arterial hypertension.

OBJECTIVE: Pulmonary arterial hypertension (PAH), caused by pulmonary artery remodelling and increased pulmonary vascular resistance (PVR) due to an unknown mechanism, is an intractable disease with a poor prognosis. The recent development of PAH-specific treatment medications may allow for higher PVR reduction than previously achieved. This study aimed to identify the prognostic significance of follow-up PVR levels achieved shortly after the initiation of targeted treatment in patients with idiopathic/heritable pulmonary arterial hypertension (I/H-PAH). METHODS: We analysed the data of all patients with I/H-PAH admitted to our hospital between 1998 and 2019. We collected data at baseline and during the first invasive haemodynamic evaluation. The primary outcome was death or lung transplantation. RESULTS: Of the 133 treatment-naïve patients enrolled in this study, 47 experienced adverse events during a median follow-up period of 6.4 (IQR 3.5-11.5) years. The median time interval to first follow-up from diagnosis was 162 (IQR 117-253) days. Incidence of the primary outcome was significantly lower in patients who achieved low PVR at follow-up. Of risk factors evaluated at follow-up, the multivariate Cox regression analysis revealed PVR as an independent predictor of the primary outcome (HR 1.103, 95% CI 1.029 to 1.183; p=0.006). The results were consistent across risk profiles according to the simplified risk stratification recommended by the European Society of Cardiology and European Respiratory Society guidelines. CONCLUSION: Follow-up PVR was an independent predictor of transplant-free survival in patients with I/H-PAH. Evaluation of haemodynamic status shortly after initiating treatment may help predict long-term prognosis.

Prognostic value of right ventricular native T1 mapping in pulmonary arterial hypertension.

BACKGROUND: Right ventricular function is an important prognostic marker for pulmonary arterial hypertension. Native T1 mapping using cardiovascular magnetic resonance imaging can characterize the myocardium, but accumulating evidence indicates that T1 values of the septum or ventricular insertion points do not have predictive potential in pulmonary arterial hypertension. We aimed to elucidate whether native T1 values of the right ventricular free wall (RVT1) can predict poor outcomes in patients with pulmonary arterial hypertension. METHODS: This retrospective study included 30 patients with pulmonary arterial hypertension (median age, 45 years; mean pulmonary artery pressure, 41±13 mmHg) and 16 healthy controls (median age, 43 years) who underwent native T1 mapping. RVT1 was obtained from the inferior right ventricular free wall during end systole. RESULTS: Patients with pulmonary arterial hypertension had significantly higher native RVT1 than did controls (1384±74 vs. 1217±57 ms, p<0.001). Compared with T1 values of the septum or ventricular insertion points, RVT1 correlated better with the effective right ventricular elastance index (R = -0.53, p = 0.003), ventricular-arterial uncoupling (R = 0.46, p = 0.013), and serum brain natriuretic peptide levels (R = 0.65, p<0.001). Moreover, the baseline RVT1 was an accurate predictor of the reduced right ventricular ejection fraction at the 12-month follow-up (delta -3%). RVT1 was independently associated with composite events of death or hospitalization from any cause (hazard ratio = 1.02, p = 0.002). CONCLUSIONS: RVT1 was predictive of right ventricular performance and outcomes in patients with pulmonary arterial hypertension. Thus, native T1 mapping in the right ventricular free wall may be an effective prognostic method for pulmonary arterial hypertension.

Aryl hydrocarbon receptor is essential for the pathogenesis of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by arteriopathy in the small to medium-sized distal pulmonary arteries, often accompanied by infiltration of inflammatory cells. Aryl hydrocarbon receptor (AHR), a nuclear receptor/transcription factor, detoxifies xenobiotics and regulates the differentiation and function of various immune cells. However, the role of AHR in the pathogenesis of PAH is largely unknown. Here, we explore the role of AHR in the pathogenesis of PAH. AHR agonistic activity in serum was significantly higher in PAH patients than in healthy volunteers and was associated with poor prognosis of PAH. Sprague-Dawley rats treated with the potent endogenous AHR agonist, 6-formylindolo[3,2-b]carbazole, in combination with hypoxia develop severe pulmonary hypertension (PH) with plexiform-like lesions, whereas Sprague-Dawley rats treated with the potent vascular endothelial growth factor receptor 2 inhibitors did not. Ahr-knockout (Ahr-/- ) rats generated using the CRISPR/Cas9 system did not develop PH in the SU5416/hypoxia model. A diet containing Qing-Dai, a Chinese herbal drug, in combination with hypoxia led to development of PH in Ahr+/+ rats, but not in Ahr-/- rats. RNA-seq analysis, chromatin immunoprecipitation (ChIP)-seq analysis, immunohistochemical analysis, and bone marrow transplantation experiments show that activation of several inflammatory signaling pathways was up-regulated in endothelial cells and peripheral blood mononuclear cells, which led to infiltration of CD4+ IL-21+ T cells and MRC1+ macrophages into vascular lesions in an AHR-dependent manner. Taken together, AHR plays crucial roles in the development and progression of PAH, and the AHR-signaling pathway represents a promising therapeutic target for PAH.

Pathological and clinical effects of interleukin-6 on human myocarditis.

BACKGROUND: Numerous basic studies have shown a relationship between interleukin-6 (IL-6) and the development or severity of myocarditis. However, there has been no study in which the effect of IL-6 levels in patients with myocarditis was evaluated. METHODS: We enrolled control patients (n = 12) and consecutive patients with acute myocarditis (n = 13), including lymphocytic, eosinophilic, and giant cell myocarditis, and investigated the pathological and clinical effects of IL-6 on human myocarditis. RESULTS: The serum IL-6 level in patients with myocarditis (16.7 [9.9, 103.8] pg/mL) was significantly higher than that in the control patients (1.4 [1.0, 1.9] pg/mL) (P<0.001). Immunohistochemical analysis showed that IL-6 was expressed in infiltrating inflammatory cells of endomyocardial biopsy samples from all patients with myocarditis. Moreover, the log-transformed value of serum IL-6 level showed significant positive correlations with serum creatine kinase (CK) level, CK-MB level, peak CK level, peak CK-MB level and C-reactive protein level (all P ≤ 0.005) and a negative correlation with the left ventricular (LV) ejection fraction (p = 0.014). We divided the patients with myocarditis into a low IL-6 group (9.9 [4.5, 14.2] pg/dL, n = 7) and a high IL-6 group (108.9 [51.1, 130.9] pg/dL, n = 6). The degree of infiltration of IL-6-expressing inflammatory cells in myocardial samples obtained from patients in the high IL-6 group was significantly more severe than that in samples obtained from patients in the low IL-6 group. Furthermore, patients in the high IL-6 group significantly more frequently received catecholamine therapy (P = 0.005), venoarterial extracorporeal membrane oxygenation (P = 0.029), and artificial respirator support (P = 0.021) in the acute phase of myocarditis. CONCLUSION: The results suggest that there is a strong impact of IL-6 on cardiac injury and dysfunction in patients with myocarditis.

Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models.

The majority of the conventional techniques that are utilized for investigating the pathogenesis of cardiovascular disease in preclinical animal models do not permit microlevel assessment of in situ cardiomyocyte and microvascular functions. Therefore, it has been difficult to establish whether cardiac dysfunction in complex multiorgan disease states, such as heart failure with preserved ejection fraction and pulmonary hypertension, have their origins in microvascular dysfunction or rather in the cardiomyocyte. Herein, we describe our approach of utilizing synchrotron radiation microangiography to, first, ascertain whether the growth hormone secretagogue (GHS) hexarelin is a vasodilator in the coronary circulation of normal and anesthetized Sprague-Dawley rats, and next investigate if hexarelin is able to prevent the pathogenesis of right ventricle (RV) dysfunction in pulmonary hypertension in the sugen chronic hypoxia model rat. We show that acute hexarelin administration evokes coronary microvascular dilation through GHS-receptor 1a and nitric oxide, and through endothelium-derived hyperpolarization. Previous work indicated that chronic exogenous administration of ghrelin largely prevented the pathogenesis of pulmonary hypertension in chronic hypoxia and in monocrotaline models. Unexpectedly, chronic hexarelin administration prior to sugen chronic hypoxia did not prevent RV hypertrophy or RV cardiomyocyte relaxation impairment. Small-angle X-ray scattering revealed that super relaxed myosin filaments contributed to diastolic dysfunction, and that length-dependent activation might contribute to sustained contractility of the RV. Thus, synchrotron-based imaging approaches can reveal novel insights into cardiac and coronary functions in vivo.

Pristane/Hypoxia (PriHx) Mouse as a Novel Model of Pulmonary Hypertension Reflecting Inflammation and Fibrosis.

BACKGROUND: Pulmonary arterial hypertension (PAH), particularly connective tissue disease-associated PAH (CTD-PAH), is a progressive disease and novel therapeutic agents based on the specific molecular pathogenesis are desired. In the pathogenesis of CTD-PAH, inflammation, immune cell abnormality, and fibrosis play important roles. However, the existing mouse pulmonary hypertension (PH) models do not reflect these features enough. The relationship between inflammation and hypoxia is still unclear.Methods and Results:Intraperitoneal administration of pristane, a kind of mineral oil, and exposure to chronic hypoxia were combined, and this model is referred to as pristane/hypoxia (PriHx) mice. Hemodynamic and histological analyses showed that the PriHx mice showed a more severe phenotype of PH than pristane or hypoxia alone. Immunohistological and flow cytometric analyses revealed infiltration of immune cells, including hemosiderin-laden macrophages and activated CD4+helper T lymphocytes in the lungs of PriHx mice. Pristane administration exacerbated lung fibrosis and elevated the expression of fibrosis-related genes. Inflammation-related genes such asIl6andCxcl2were also upregulated in the lungs of PriHx mice, and interleukin (IL)-6 blockade by monoclonal anti-IL-6 receptor antibody MR16-1 ameliorated PH of PriHx mice. CONCLUSIONS: A PriHx model, a novel mouse model of PH reflecting the pathological features of CTD-PAH, was developed through a combination of pristane administration and exposure to chronic hypoxia.

Development of Pulmonary Arterial Hypertension in a Patient Treated with Qing-Dai (Chinese Herbal Medicine).

Pulmonary arterial hypertension (PAH) is a rare, devastating disease, characterized by elevated pulmonary arterial pressure due to pulmonary microvascular obstruction, which can result in heart failure and death. PAH can be associated with exposure to certain drugs or toxins. We herein report a case in which PAH developed in a patient with refractory ulcerative colitis during treatment with "Qing-Dai," a Chinese herbal medicine. The patient's PAH improved after the discontinuation of Qing-Dai.

Prolonged QRS duration as a predictor of right ventricular dysfunction after balloon pulmonary angioplasty.

BACKGROUND: Balloon pulmonary angioplasty (BPA) has shown beneficial effects for chronic thromboembolic pulmonary hypertension (CTEPH). However, previous studies have shown less cardiac output improvement and symptoms remaining after BPA, implying poor right ventricular (RV) function recovery. Therefore, we investigated the residual RV dysfunction after BPA to reveal risk factors, clinical effects, and possible underlying histopathological mechanisms. METHODS AND RESULTS: We investigated 61 consecutive CTEPH patients who underwent cardiovascular magnetic resonance before and 3 and 12 months after BPA series. Residual dysfunction (RD) of RV was defined as RV end-diastolic volume index >100 ml/m2 or RV ejection fraction (EF) <45% at 12-month follow-up. Patients were divided into RD (44%) and normalized dysfunction (ND) (56%) groups. Compared with the ND group, the RD group had significantly worse World Health Organization (WHO) functional class at follow-up. No significant hemodynamic differences were observed between the groups. On multivariable logistic regression analysis, male sex (odds ratio [OR] 12.5, p = 0.004) and prolonged QRS duration (OR 1.08, p = 0.029) were independently associated with residual RV dysfunction. Additionally, RV histopathology in 11 CTEPH autopsy cases showed that QRS duration was correlated with RV fibrosis area. CONCLUSIONS: Relatively high percentage (44%) of residual RV dysfunction with worse WHO functional class was observed in CTEPH patients even after BPA. Prolonged QRS duration may predict poor recovery in RV function after BPA.

Successful multi-step catheter intervention for thrombotic inferior vena cava filter retrieval.

A 45-year-old man, who was implanted with an inferior vena cava (IVC) filter in his infrarenal IVC, had a complication of deep vein thrombosis (DVT) propagation from the IVC, beyond the IVC filter, to the right calf and left external iliac veins. The entire IVC filter was covered with a massive thrombus. We first decided to retrieve the IVC filter itself, which was suspected of causing metallic allergy. The thrombotic IVC filter was successfully retrieved using multi-step catheter intervention. To our knowledge, this is the first case report to describe successful multi-step catheter intervention for retrieval of an IVC filter covered with a massive thrombus. .

Beneficial Effect of Endovascular Treatment on Villalta Score in Japanese Patients With Chronic Iliofemoral Venous Thrombosis and Post-Thrombotic Syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS), the most common complication of deep venous thrombosis (DVT), develops in ≥50% of patients with iliofemoral DVT. However, the benefit of endovascular treatment in Japanese patients with chronic DVT and PTS remains unclear. Methods and Results: Between June 2014 and May 2016, endovascular treatment was performed in 11 consecutive Japanese patients with chronic iliofemoral DVT and PTS refractory to anticoagulant therapy and elastic compression stockings. We evaluated the technical success rate, complications, patency, Villalta score, calf circumference, and popliteal vein reflux in both the acute stage (the day following endovascular treatment) and chronic stage (after 6 months). Imaging follow-up included venous duplex scanning and/or magnetic resonance venography. The technical success rate was 81.8%, without complications. In patients with successful intervention, the Villalta score improved significantly, from 9.0±3.7 preoperatively to 3.6±2.5 in the acute phase (P<0.01) and 2.9±2.1 in the chronic phase (P<0.001). The bilateral difference in lower thigh circumference also improved significantly, from 2.6±1.0 cm preoperatively to 1.4±1.0 cm in the chronic phase (P<0.001). However, popliteal vein reflux did not improve. In patients with successful intervention, venous patency rate was 100% at 6 months post-intervention. CONCLUSIONS: Endovascular treatment is safe and effective in Japanese patients with chronic iliofemoral DVT and PTS.

Association of New York Heart Association functional class IV symptoms at admission and clinical features with outcomes in patients hospitalized for acute heart failure syndromes.

BACKGROUND: It remains unclear whether there are subgroups of acute heart failure syndromes (AHFS) patients in whom New York Heart Association (NYHA) class IV symptoms at admission is related to a higher risk of mortality because of the heterogeneity of this patient population. The aim of this study was to evaluate the association of NYHA class IV symptoms at baseline with in-hospital mortality in subgroups of patients with AHFS. METHODS AND RESULTS: Of the 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 4786 patients were included in this analysis. The primary endpoint was in-hospital all-cause death. NYHA class IV at baseline was detected in 44.3% of the patients. The all-cause death rate was significantly higher in patients with NYHA class IV than in those with NYHA class II or III (9.0% vs. 4.3%, P<0.001). To examine the heterogeneity of the association between NYHA class IV symptoms at baseline and in-hospital mortality, subgroup analyses were performed. As a result, the presence of NYHA class IV symptoms on admission was associated with a significantly higher risk of all-cause death in patients aged ≥75years, female patients, patients without an idiopathic dilated etiology, and patients with preserved ejection fraction (EF). CONCLUSIONS: This study demonstrated that an age≥75years, female gender, the absence of idiopathic dilated etiology, and a preserved EF should be considered when assessing the clinical significance of NYHA class IV symptoms in relation to the risk of in-hospital mortality in patients hospitalized for AHFS.

Efficacy and safety of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension guided by cone-beam computed tomography and electrocardiogram-gated area detector computed tomography.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease characterized by chronic obstructive thrombus and pulmonary hypertension. Balloon pulmonary angioplasty (BPA), an emerging alternative catheter-based treatment for inoperable patients with CTEPH, has not yet been standardised, especially for lesion assessment in distal pulmonary arteries. Recent advancement in computed tomography enables distal CTEPH lesions to be visualized. METHODS: We retrospectively studied 80 consecutive patients with inoperable CTEPH who received BPA guided by cone-beam computed tomography (CT) (CBCT) or electrocardiogram (ECG)-gated area detector CT (ADCT) for target lesion assessment. We collected clinical and hemodynamic data, including procedural complications, before BPA and at 3 months and 1year after BPA. RESULTS: Three hundred eight-five BPA sessions (4.8 sessions/patient) were performed for the lesions of subsegmental arteries (1155 lesions), segmental arteries (738 lesions), and lobar arteries (4 lesions) identified by CBCT or ECG-gated ADCT. Significant improvements in the symptoms, 6-min walk distance, brain natriuretic peptide level, exercise capacity, and haemodynamics were observed 3 months and 1year after BPA. No cases of death or cardiogenic shock with a low rate of severe wire perforation (0.3%) and severe reperfusion oedema (0.3%) were observed. CONCLUSIONS: BPA guided by CBCT or ECG-gated ADCT is effective and remarkably safe in patients with CTEPH . These new advanced CT techniques may be useful in pre-BPA target lesion assessment.

Thyroid Echography-induced Thyroid Storm and Exacerbation of Acute Heart Failure.

Hyperthyroidism and thyroid storm affect cardiac circulation in some conditions. Several factors including trauma can induce thyroid storms. We herein describe the case of a 57-year-old woman who experienced a thyroid storm and exacerbation of acute heart failure on thyroid echography. She initially demonstrated a good clinical course after medical rate control for atrial fibrillation; however, thyroid echography for evaluating hyperthyroidism led to a thyroid storm and she collapsed. A multidisciplinary approach stabilized her thyroid hormone levels and hemodynamics. Thus, the medical staff should be prepared for a deterioration in the patient's condition during thyroid echography in heart failure patients with hyperthyroidism.