Adult-onset idiopathic peripheral pulmonary artery stenosis.

BACKGROUND: Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS. METHODS: We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected. RESULTS: 44 patients (median (interquartile range) age 39 (29-57) years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44 versus 40 mmHg; p<0.001) and pulmonary vascular resistance (760 versus 514 dyn·s·cm-5; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5-99.6%), 89.0% (95% CI 68.9-96.4%) and 67.0% (95% CI 41.4-83.3%), respectively. CONCLUSIONS: In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty.

Case report: Pathological differences in pulmonary arterial hypertension in long-term responders to calcium channel blockers.

Background: This study investigates the pulmonary arterial histopathology in patients with idiopathic pulmonary arterial hypertension (IPAH) and acute vasoreactive phenotype, who demonstrated long-term survival (>30 years) and incidental death from causes other than PAH progression. The pathological changes observed in these patients were compared with those in patients with bone morphogenetic protein receptor type 2 (BMPR2) mutation. Case Presentation: We present two cases of patients with pulmonary arterial hypertension (PAH) who died incidentally from causes unrelated to PAH progression. We report compares pulmonary arterial histopathology in long-term survivors of CCB-responsive PAH patient and a hereditary PAH patient with a BMPR2 mutation. Lung specimens were analyzed using the Heath and Edwards (HE) classification and percentage muscular wall thickness (%MWT) of pulmonary arterioles. A significant difference in the severity of grading (p = 0.0001) and distribution between grades 1-2, 4 (p = 0.001), and 5 (p = 0.014) was observed between both patients. These findings suggest differential vascular pathology between the two cases, with CCB responders displaying more mild illness lesions compared to BMPR2 mutant patients. Conclusion: The study revealed that CCB responders exhibit more mild illness vascular lesions than BMPR2 mutant patients despite their long-term survival, suggesting a difference in vascular pathology between the two phenotypes.

Usefulness of Longitudinal Strain to Assess Cancer Therapy-Related Cardiac Dysfunction and Immune Checkpoint Inhibitor-Induced Myocarditis.

Longitudinal strain (LS) measured by echocardiography has been reported to be useful not only for the diagnosis and risk stratification of various cardiac diseases, but also in cardio-oncology. Most previous studies have been conducted on patients undergoing treatment with anthracyclines and human epidermal growth factor receptor 2-targeted therapies. Existing guidelines recommend that global LS (GLS) should be measured before and after the administration of cancer drugs. This recommendation is based on many reports showing that a decline in GLS is indicative of early or mild cancer therapy-related cardiac dysfunction. The main purpose of this article is to provide insight into the importance of LS in patients undergoing cancer treatment and highlight the role of LS evaluation in patients undergoing immune checkpoint inhibitor (ICI) treatment, which is being used with increasing frequency. Among cancer drug therapies, immune checkpoint inhibitors (ICIs) have an important place in cancer treatment and are used for the treatment of many types of cancer. Although the efficacy of ICIs in cancer treatment has been reported, immune-related adverse events (irAEs) have also been reported. Among these irAEs, cardiovascular complications, although rare, are recognized as important adverse events that may result in ICI treatment discontinuation. Myocarditis is one severe adverse event associated with ICIs, and it is important to standardize diagnostic and therapeutic approaches to it. Several studies have reported a relationship between LS and cardiac complications associated with ICIs which may contribute to the early diagnosis of ICI-induced cardiac complications.

How do the 2022 European Society of Cardiology/European Respiratory Society guidelines modify the diagnosis of portopulmonary hypertension in patients with cirrhosis complicated by portal hypertension? A post hoc analysis.

The vertical and horizontal broken lines indicate the pre-revised criteria, whereas the vertical and horizontal solid lines indicate the 2022 European Society of Cardiology/European Respiratory Society criteria.

SATISFY-JP, a phase II multicenter open-label study on Satralizumab, an anti-IL-6 receptor antibody, use for the treatment of pulmonary arterial hypertension in patients with an immune-responsive-phenotype: Study protocol.

Pulmonary arterial hypertension (PAH), an intractable disease with a poor prognosis, is commonly treated using pulmonary vasodilators modulating the endothelin, cGMP, and prostacyclin pathway. Since the 2010s, drugs for treating pulmonary hypertension based on mechanisms other than pulmonary vasodilation have been actively developed. However, precision medicine is based on tailoring disease treatment to particular phenotypes by molecular-targeted drugs. Since interleukin-6 (IL-6) is involved in the development of PAH in animal models, and some patients with PAH have elevated IL-6 levels, the cytokine is expected to obtain potentials for therapeutic targeting. Accordingly, we identified a phenotype with elevated cytokine activity of the IL-6 family in the PAH population by combining case data extracted from the Japan Pulmonary Hypertension Registry with a comprehensive analysis of 48 cytokines using artificial intelligence clustering techniques. Including an IL-6 threshold ≥2.73 pg/mL as inclusion criteria for reducing the risk of insufficient efficacy, an investigator-initiated clinical study using satralizumab, a recycling anti-IL6 receptor monoclonal antibody, for patients with an immune-responsive phenotype is underway. This study is intended to test whether use of patient biomarker profile can identify a phenotype responsive to anti-IL6 therapy.

Current clinical understanding and effectiveness of portopulmonary hypertension treatment.

Portopulmonary hypertension (PoPH) is a rare subtype of Group 1 pulmonary arterial hypertension (PAH) with a poor prognosis. According to the most up-to-date definition, PoPH is characterized by a mean pulmonary arterial pressure (PAP) of >20 mmHg at rest, a pulmonary artery wedge pressure of ≤15 mmHg, and a pulmonary vascular resistance (PVR) of >2 Wood units with portal hypertension. Like PAH, PoPH is underpinned by an imbalance in vasoactive substances. Therefore, current guidelines recommend PAH-specific therapies for PoPH treatment; however, descriptions of the actual treatment approaches are inconsistent. Given the small patient population, PoPH is often studied in combination with idiopathic PAH; however, recent evidence suggests important differences between PoPH and idiopathic PAH in terms of hemodynamic parameters, treatment approaches, survival, socioeconomic status, and healthcare utilization. Therefore, large, multi-center registry studies are needed to examine PoPH in isolation while obtaining statistically meaningful results. PoPH has conventionally been excluded from clinical drug trials because of concerns over hepatotoxicity. Nevertheless, newer-generation endothelin receptor antagonists have shown great promise in the treatment of PoPH, reducing PVR, PAP, and World Health Organization functional class without causing hepatotoxicity. The role of liver transplantation as a treatment option for PoPH has also been controversial; however, recent evidence shows that this procedure may be beneficial in this patient population. In the future, given the shortage of liver donors, predictors of a favorable response to liver transplantation should be determined to select the most eligible patients. Collectively, advances in these three areas could help to standardize PoPH treatment in the clinic.

Usefulness of Global Longitudinal Strain-Guided Management in Preventing Human Epidermal Growth Factor Receptor 2 (HER2) Inhibitor-Induced Myocardial Damage.

Background: Trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, is a specific first-line treatment for patients with HER2-positive cancers. Cardiac dysfunction is among the most problematic adverse events associated with trastuzumab. Although regular echocardiographic screening is recommended for early detection of cardiac damage, few reports have investigated the validity of echocardiographic screening in chemotherapy. Therefore, the aim of this study was to determine whether a GLS-guided management approach could reduce cardiotoxicity and discontinuation of trastuzumab chemotherapy. Methods and Results: To evaluate the usefulness of global longitudinal strain (GLS)-guided cardioprotective interventions, we retrospectively analyzed 67 patients treated with trastuzumab who underwent structured echocardiographic assessments before and after 1, 3, and 6 courses of trastuzumab administration. If a >15% relative decrease in GLS was identified, cardioprotective agents were administered. Thirty (44.8%) patients had breast cancer; the remaining patients had salivary gland cancer. The median observation period for the intervention group was 304 days from the initial evaluation. Nineteen (28.4%) patients exhibited a >15% relative decrease in GLS, and consequently received cardioprotective agents. The incidence of trastuzumab discontinuation for cardiogenic reasons was significantly lower among patients receiving GLS-guided interventions than among those not receiving the intervention (2.4% vs. 24.0%; P=0.009). The incidence of a subsequent decline in left ventricular ejection fraction was lower among patients receiving the intervention than among those not receiving the intervention (4.8% vs. 24.0%; P=0.04). Conclusions: GLS-guided cardioprotective intervention significantly decreased the incidence of trastuzumab discontinuation.

Clinical Management and Outcomes of Patients With Portopulmonary Hypertension Enrolled in the Japanese Multicenter Registry.

Background: Portopulmonary hypertension (PoPH) is one of the major underlying causes of pulmonary arterial hypertension (PAH). However, PoPH, especially treatment strategies, has been poorly studied. Therefore, this study evaluated current treatments for PoPH, their efficacy, and clinical outcomes of patients with PoPH. Methods and Results: Clinical data were collected for patients with PoPH who were enrolled in the Japan Pulmonary Hypertension Registry between 2008 and 2021. Hemodynamic changes, functional class, and clinical outcomes were compared between patients with PoPH treated with monotherapy and those treated with combination therapies. Clinical data were analyzed for 62 patients with PoPH, including 25 treatment-naïve patients, from 21 centers in Japan. In more than half the patients, PAH-specific therapy improved the New York Heart Association functional class by at least one class. The 3- and 5-year survival rates of these patients were 88.5% (95% confidence interval [CI] 76.0-94.7) and 80.2% (95% CI 64.8-89.3), respectively. Forty-one (66.1%) patients received combination therapy. Compared with patients who had received monotherapy, the mean pulmonary arterial pressure, pulmonary vascular resistance, and cardiac index were significantly improved in patients who had undergone combination therapies. Conclusions: Combination therapy was commonly used in patients with PoPH with a favorable prognosis. Combination therapies resulted in significant hemodynamic improvement without an increased risk of side effects.

Routine assessment of cardiotoxicity in patients undergoing long-term immune checkpoint inhibitor therapy.

The indications for immune checkpoint inhibitors (ICIs) are expanding in cancer drug therapy, and while cardiac events associated with ICIs are often fatal, there are few reports regarding cardiac complications associated with long-term ICI therapy. We aimed to study cardiac complications in patients undergoing long-term ICI therapy. From the database of our local cardio-oncology unit, we enrolled patients with cancer undergoing ICI therapy for more than 6 months and for whom cardiologists continuously performed routine follow-ups. We defined the primary endpoint as discontinuation of ICI due to cardiac events. We also analyzed changes in cardiac biomarkers and echocardiographic parameters. We retrospectively analyzed 55 consecutive patients (43 males, mean age: 65 ± 11 years) treated with ICI therapy in our hospital between January 2017 and June 2021. None of the patients discontinued ICI therapy due to cardiac events more than 6 months after treatment was initiated. Among the participants, we observed four patients with elevated serum troponin I levels, seven patients with decreased global longitudinal strain values, and two patients with elevated plasma brain natriuretic peptide levels. No patient required drug intervention for these cardiac events; furthermore, there were no cases of clinically diagnosed myocarditis. In the present study, there were no cardiac events causing ICI discontinuation in patients undergo ICI therapy for more than 6 months.

Impact of extracorporeal CPR with transcatheter heart pump support (ECPELLA) on improvement of short-term survival and neurological outcome in patients with refractory cardiac arrest - A single-site retrospective cohort study.

Aim: Extracorporeal cardiopulmonary resuscitation (E-CPR) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a novel lifesaving method for refractory cardiac arrest. Although VA-ECMO preserves end-organ perfusion, it may affect left ventricular (LV) recovery due to increased LV load. An emerging treatment modality, ECPELLA, which combines VA-ECMO and a transcatheter heart pump, Impella, can simultaneously provide circulatory support and LV unloading. In this single-site cohort study, we assessed impact of ECPELLA support on clinical outcomes of refractory cardiac arrest patients. Method: We retrospectively reviewed 165 consecutive cardiac arrest patients, who underwent E-CPR by VA-ECMO with or without intra-aortic balloon pump (IABP) or ECPELLA from January 2012 to September 2021. We assessed 30-day survival rate, neurological outcome, hemodynamic data, and safety profiles including hemolysis, acute kidney injury, blood transfusion and embolic cerebral infarction. Results: Among 165 E-CPR patients, 35 patients were supported by ECPELLA, and 130 patients were supported by conventional VA-ECMO with or without IABP. Following propensity score matching of 30 ECPELLA and 30 VA-ECMO patients, the 30-day survival (ECPELLA: 53%, VA-ECMO: 20%, p < 0.01) and favorable neurological outcome determined by the Cerebral Performance Category score 1 or 2 (ECPELLA: 33%, VA-ECMO: 7%, p < 0.01) were significantly higher with ECPELLA. Patients receiving ECPELLA also showed significantly higher total mechanical circulatory support flow and lower arterial pulse pressure for the first 3 days (p < 0.01) of treatment. There were no statistical differences in safety profiles between treatment groups. Conclusion: ECPELLA may be associated with improved 30-day survival and neurological outcome in patients with refractory cardiac arrest.

Long-term safety of a structured transition protocol from parenteral prostanoids to selexipag in pulmonary arterial hypertension.

There was no structured method for safely transition from parenteral prostanoids to oral medication. We enrolled 37 idiopathic/hereditary pulmonary arterial hypertension patients receiving triple combination therapy including parenteral prostanoids into structured transition program to oral selexipag. Four (10.8%) patients successfully transitioned under the protocol, and all of them presented long-term safety.

Inappropriate sinus tachycardia-induced cardiomyopathy with severe functional mitral regurgitation and successful treatment with ivabradine.

Ivabradine increases stroke volume, but does not have a negative impact on blood pressure (BP). Thus, a patient with low BP can benefit from treatment with ivabradine. A 72-year-old Japanese woman with asthma and chronic bronchitis presented with dyspnea. Her heart rate (HR) was 126 beats per minute and an electrocardiogram showed sinus tachycardia. The chest X-ray showed cardiomegaly and pulmonary congestion. A transthoracic echocardiogram (TTE) showed reduced left ventricular ejection function (LVEF) and severe functional mitral regurgitation (MR). We diagnosed her with inappropriate sinus tachycardia (IST) and heart failure (HF) due to tachycardia-induced cardiomyopathy. After resolving the pulmonary congestion with diuretics, we administered a minimum dose of bisoprolol, which resulted in re-exacerbation of the HF. Because IST was persistent, we initiated treatment with ivabradine. As soon as ivabradine was started, the HR decreased, the BP gradually increased, and HF compensation was achieved. Bisoprolol was continued and losartan was started. In summary, we used ivabradine for a patient with tachycardia, low BP, a low LVEF, and severe MR. By optimizing the medical therapy, exercise tolerance improved and she was discharged. The serum brain natriuretic peptide was significantly reduced and TTE showed an improved LVEF and reduced MR. .

Comparison of left ventricular pacing performance among pre-shaped guidewires designed for transfemoral-approach transcatheter aortic valve implantation.

TAVI is an established therapy for patients with severe aortic stenosis. Rapid or control pacing is necessary for TAVI, and most centers are familiar with right ventricular (RV) pacing. Although there are several reports on the efficacy and safety of LV pacing, they are still few. In addition, LV pacing has not been studied for different LV guidewires. Our aim is to study the effectiveness of left ventricular (LV) pacing and the thresholds of LV guidewires in patients who underwent transcatheter aortic valve implantation (TAVI). We retrospectively analyzed 252 consecutive patients who underwent trans-femoral TAVI (TF-TAVI) with LV pacing in our institute between December 2017 and November 2020. We excluded 48 patients from the total cohort due to TAVI with RV pacing, and the remaining 204 patients were analyzed (52 males, mean age 85 ± 5 years). Among them, 202 patients (99.0%) had successful LV pacing. In the two patients with failed LV pacing, SAFARI2™ Small was used. The CONFIDA™ group (n = 34) showed a significantly lower threshold than the SAFARI2™ group (n = 163) (median 3.0 vs. 5.0 V; P = 1.1 × 10-7). LV pacing with Lunderquist® was successful in all patients (n = 7). LV pacing in TAVI was an effective and safe strategy. CONFIDA™ wire may be particularly well suited for LV pacing in TAVI.

Longitudinal Strain and Troponin I Elevation in Patients Undergoing Immune Checkpoint Inhibitor Therapy.

Background: Immune checkpoint inhibitors (ICIs) are a central part of cancer therapy; however, cardiac complications, such as myocarditis, have the potential for significant morbidity and mortality. Within this population, the clinical significance of longitudinal strain (LS) remains unknown. Objectives: This study sought to define the changes in LS in ICI-treated patients, and their associations with high-sensitivity troponin I (hsTnI) and myocarditis. Methods: We conducted a retrospective cohort study of patients who received ICIs at our hospital from April 2017 to September 2021. All patients underwent echocardiography and blood sampling at standardized time intervals. We measured the changes in global and regional LS before and after ICI administration. Age- and sex-adjusted Cox regression analysis was used to evaluate the association between LS and elevations in hsTnI and myocarditis. Results: In a cohort of 129 patients with a median follow-up period of 170 (IQR: 62-365) days; 6 and 18 patients had myocarditis and hsTnI elevation, respectively. In an age- and sex-adjusted Cox proportional hazards model, an early relative worsening of ≥10% in the basal and mid LS and ≥15% in global LS was associated with hsTnI elevation. Relative reductions in LS were not significantly associated with myocarditis; however, 4 of the 6 patients with myocarditis had relative reduction of ≥10% in the basal LS. Conclusions: An early worsening in the global and regional LS was associated with increased hsTnI in patients receiving ICIs. Assessment of LS early after ICI administration should be further studied as a strategy for risk stratification of ICI-treated patients.

Predictors of hypoxemia in type-B acute aortic syndrome: a retrospective study.

Acute aortic syndrome (AAS) can be life-threatening owing to a variety of complications, and it is managed in the intensive care unit (ICU). Although Stanford type-B AAS may involve hypoxemia, its predictors are not yet clearly understood. We studied clinical factors and imaging parameters for predicting hypoxemia after the onset of type-B AAS. We retrospectively analyzed patients diagnosed with type-B AAS in our hospital between January 2012 and April 2020. We defined hypoxemia as PaO2/FiO2 ≤ 200 within 7 days after AAS onset and used logistic regression analysis to evaluate prognostic factors for hypoxemia. We analyzed 224 consecutive patients (140 males, mean age 70 ± 14 years) from a total cohort of 267 patients. Among these, 53 (23.7%) had hypoxemia. The hypoxemia group had longer ICU and hospital stays compared with the non-hypoxemia group (median 20 vs. 16 days, respectively; p = 0.039 and median 7 vs. 5 days, respectively; p < 0.001). Male sex (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.24-6.63; p = 0.014), obesity (OR 2.36; 95% CI 1.13-4.97; p = 0.023), patent false lumen (OR 2.33; 95% CI 1.09-4.99; p = 0.029), and high D-dimer level (OR 1.01; 95% CI 1.00-1.02; p = 0.047) were independently associated with hypoxemia by multivariate logistic analysis. This study showed a significant difference in duration of ICU and hospital stays between patients with and without hypoxemia. Furthermore, male sex, obesity, patent false lumen, and high D-dimer level may be significantly associated with hypoxemia in patients with type-B AAS.

The first described case of late infective endocarditis after implantation of Figulla Flex â ¡ ASD occluder.

Infective endocarditis is one of the complications following the percutaneous occlusion of an atrial septal defect (ASD) with a closure device. To the best of our knowledge, no case reports have been published of infective endocarditis associated with the Figulla Flex Ⅱ ASD occluder (FSO; Occlutech GmbH, Jena, Germany). We present the case of a 50-year-old woman who underwent a transcatheter closure of an ASD with FSO almost 2 years prior to presentation to our institution. Echocardiography showed a mobile vegetation (20 × 10 mm), and her blood culture grew ß-hemolytic streptococci. Magnetic resonance imaging revealed acute cerebral infarction. Those findings were diagnosed as late infective endocarditis associated with the ASD closure device. The patient was treated with antibiotics and underwent surgical removal of the FSO, which showed incomplete endothelialization, and surgical repair of ASD. After surgery, the patient made a complete recovery without complications or residual shunts. This case highlights the risk of late infective endocarditis in patients after closure of ASD with an FSO with incomplete endothelialization. .

Treatment with a Direct Oral Anticoagulant for Nonbacterial Thrombotic Endocarditis.

We herein report a case of nonbacterial thrombotic endocarditis (NBTE) in a patient with previously undiagnosed lung cancer. A 62-year-old woman presented to our hospital with multiple cerebral infarctions. There was no evidence of valvular heart disease or vegetations. Whole-leg ultrasonography revealed deep vein thrombosis of the left peroneal vein. We administered direct oral anticoagulants (DOACs) for a presumed diagnosis of paradoxical embolisms caused by patent foramen ovale. Unfortunately, she experienced further embolization and died. At a postmortem examination, she was diagnosed with NBTE and metastatic adenocarcinoma of the lung. Our experience with this patient suggests that DOACs may be an insufficient treatment for NBTE.