Hironori Muraoka

Immunoglobulin G4–related multiple systemic aneurysms and splenic aneurysm rupture during steroid therapy

Immunoglobulin G4 (IgG4)-related disorders in various organs have recently been described, but multiple systemic aneurysms have not yet been reported. Here, we present a 68-year-old Japanese man with multiple systemic aneurysms and tumor-forming pericoronary arteritis who was undergoing low-dose corticosteroid therapy. Elevated serum IgG4 (2390 mg/dL) and IgG4-positive plasmacyte infiltration in the salivary glands led to a diagnosis of IgG4-related disease. High-dose corticosteroid therapy was initiated, whereupon the inflammatory lesions shrank. However, the large, well-developed common hepatic aneurysm and splenic aneurysm did not change. Our patient died of splenic aneurysm rupture in the sixth month of treatment. The autopsy revealed IgG4-positive plasmacyte infiltration in the coronary wall and a thinned splenic aneurysm wall. This case suggests that early high-dose corticosteroid therapy may be necessary for the treatment of IgG4-related cardiovascular disorders. A minor salivary gland biopsy might facilitate the early diagnosis of IgG4-related disease even if (18)F-fluorodeoxyglucose positron emission tomography provides no inflammatory findings.

Bosentan improved persistent pulmonary hypertension in a case after implantation of a left ventricular assist device

No medical treatment has been established to ameliorate pulmonary hypertension (PH) due to left heart disease. Heart transplantation (HTx) is thus far the definitive therapy for stage D heart failure, but concomitant PH is one of the major risk factors for death after HTx. Recently, implantation of a left ventricular assist device (LVAD) has been reported to improve PH and has become a major bridge tool for HTx. We experienced a rare case with persistent PH even after the implantation of a continuous-flow LVAD. The administration of an endothelin receptor antagonist, bosentan, significantly decreased pulmonary vascular resistance. Combination therapy with LVAD implantation and anti-PH medication may be useful for patients with stage D heart failure complicated with severe PH.

Platelet-Derived Growth Factor Receptor-Tyrosine Kinase Inhibitor, Imatinib, Is Effective for Treating Pulmonary Hypertension Induced by Pulmonary Tumor Thrombotic Microangiopathy

Pulmonary hypertension (PH) induced by pulmonary tumor thrombotic microangiopathy (PTTM) can be fatal because its rapid progression confounds diagnosis, and it is difficult to control with therapy. Here we describe a woman with symptomatic PTTM-PH accompanying gastric cancer that was suspected from perfusion scintigraphy. PTTM-PH was diagnosed by gastroesophageal endoscopy and lung biopsy after partial control of PH using the platelet-derived growth factor (PDGF) receptor (PDGFR) tyrosine kinase inhibitor, imatinib. Treatment with sildenafil and ambrisentan further decreased PH, and she underwent total gastrectomy followed by adjuvant TS-1 chemotherapy. PH did not recur before her death from metastasis. Postmortem histopathology showed recanalized pulmonary arteries where the embolized cancer masses disappeared. PDGF-A, -B, and PDGFR-α, β expression was detected in cancer cells and proliferating pulmonary vascular endothelial cells. Thus, PTTM-PH was successfully controlled using a combination of imatinib, drugs to treat pulmonary arterial hypertension, and cancer management.

Targeted therapy is required for management of pulmonary arterial hypertension after defect closure in adult patients with atrial septal defect and associated pulmonary arterial hypertension.

BACKGROUND Therapeutic strategies for pulmonary arterial hypertension (PAH) associated with atrial septal defect (ASD) remain a matter of debate. METHODS AND RESULTS We identified 5 outpatients who had been diagnosed with ASD-PAH and undergone ASD closure in combination with targeted therapy with certified PAH drugs. We assessed changes in hemodynamic parameters and exercise capacity. The combination of ASD closure and targeted therapy significantly increased systemic blood flow (Qs) from the baseline (from 3.3 ± 0.6 L/minute to 4.2 ± 1.0 L/minute, P < 0.05) with a significant improvement in the World Health Organization Functional Class (WHO-FC; from 2.8 ± 0.4 to 1.6 ± 0.5, P < 0.05). The hemodynamic data before and after ASD closure without targeted therapy showed further elevation of pulmonary vascular resistance shortly after ASD closure (678 dyne · s/cm(5) to 926 dyne · s/cm(5)) in 1 case, as well as after a long time since ASD closure (491.0 ± 53.7 dyne · s/cm(5) to 1045.0 ± 217.8 dyne · s/cm(5)) in 2 cases. This worsening was reversed after the targeted therapy, accompanied by an increase in Qs and an improvement in WHO-FC in all cases. CONCLUSIONS Targeted therapy should be added to ASD closure in adult patients with ASD-PAH.

Acute pulmonary vasoreactivity test with sildenafil or nitric monoxide before left ventricular assist device implantation

There has been no established medical therapy to ameliorate pulmonary hypertension (PH) owing to left heart disease (LHD-PH). It has recently been shown that the left ventricular assist device (LVAD) can improve LHD-PH and therefore has the potential to become a major bridge tool for heart transplantation (HTx). However, some patients still have persistent PH even after LVAD treatment. It is essential to demonstrate the reversibility of end-organ dysfunction, including PH, prior to implantable LVAD treatment, especially in Japan, because implantable LVAD treatment is indicated only as bridge to transplantation. Here we report a patient with LHD-PH whose PH was demonstrated to be reversible by the acute pulmonary vasoreactivity test (APVT) with nitrogen monoxide (NO) and the phosphodiesterase-5 inhibitor sildenafil. Both inhaled NO and sildenafil reduced pulmonary vascular resistance, but pulmonary capillary wedge pressure was increased by NO, which was conversely decreased under increased cardiac output by sildenafil. After the patient was listed as an HTx recipient, pulmonary vascular resistance recovered down to an acceptable range with LVAD treatment. Based on these findings, we suggest that the APVT with sildenafil may be a useful and safe tool to predict improvement of PH after LVAD treatment.

Reverse Remodeling Achieved by Combination Therapy With High-Dose Beta Blocker and Cardiac Resynchronization

Although both beta-blocker treatment and cardiac resynchronization therapy (CRT) have been established as the standard therapeutic strategy to achieve left ventricular reverse remodeling (LVRR) and improve prognosis in heart failure (HF) patients with systolic LV dysfunction, some patients do not respond to such treatments. We here report a HF patient with left bundle branch block due to nonischemic cardiomyopathy who did not respond to 20 mg/day of carvedilol in terms of LVRR. Subsequent CRT only achieved insufficient LVRR, and we further titrated carvedilol up to 40 mg/day. Marked LVRR was accomplished at a fixed 70 bpm heart rate under CRT, and therefore it was considered as heart rate-independent. Up-titration of beta-blocker after CRT may be necessary to induce optimal LVRR in some populations.

A case of interferon-α-induced pulmonary arterial hypertension after living donor liver transplantation

Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease characterized by elevated pulmonary vascular resistance, which results in right-heart failure. We present a case of interferon (IFN)-α-induced PAH developed after living donor liver transplantation. Although IFN is categorized as a “possible” risk factor for PAH in the current international classification, it is still under recognized. Moreover, the prognosis of IFN-induced PAH is poor in the limited number of published cases. In our case, we achieved good outcome by the withdrawal of IFN and administration of combination therapy using tadalafil, beraprost, and treprostinil. Since IFN is an important treatment option in current medical therapy, its contribution to the pathogenesis of PAH should be taken into consideration. In conclusion, our case suggests the importance of PAH screening in patients treated with IFN.

SERUM ACYLCARNITINE CONCENTRATION IS ELEVATED IN PATIENTS WITH ACUTE DECOMPENSATED HEART FAILURE

Carnitine is a key molecule for mitochondrial fatty acid β-oxidation, and previous reports have suggested beneficial effects of carnitine administration on heart failure (HF) patients. However, little is known about the change of systemic carnitine homeostasis in HF patients. We measured serum

LOW CARDIAC OUTPUT STIMULATES VASOPRESSIN RELEASE IN PATIENTS WITH STAGE D HEART FAILURE: ITS RELEVANCE TO POOR PROGNOSIS AND REVERSAL BY SURGICAL TREATMENT

Depressed cardiac output stimulates release of arginine vasopressin (AVP), but the relationship is not extensively examined between AVP levels and cardiac parameters especially in patients with stage D heart failure (HF). For stage D HF, ventricular assist device (VAD) implantation or heart

Cardiac compression by massive mediastinal haematoma due to bleeding from the ectopic bronchial artery

A 78-year-old man with a history of angina pectoris was admitted to the hospital because of congestive heart failure. An echocardiogram showed decreased left ventricular systolic function with hypokinesis of the posteroinferior wall. After medical treatment, cardiac catheterization was performed, demonstrating significant stenotic lesions in the right coronary artery and …