Cardiac sarcoidosis resembling panic disorder: a case report.

BACKGROUND: Sarcoidosis is a systemic disease of unknown etiology, in which granulomas develop in various organs, including the skin, lungs, eyes, or heart. It has been reported that patients with sarcoidosis are more likely to develop panic disorder than members of the general population. However, there are many unknown factors concerning the causal relationship between these conditions. CASE PRESENTATION: We present the case of a 57-year-old woman who appeared to have panic disorder, as she experienced repeated panic attacks induced by transient complete atrioventricular block, associated with cardiac sarcoidosis. Psychotherapy and pharmacotherapy were not effective in the treatment of her panic attacks. However, when we implanted a permanent pacemaker and initiated steroid treatment for cardiac sarcoidosis, panic attacks were ameliorated. Based on these findings, we diagnosed the patient's symptoms as an anxiety disorder associated with cardiac sarcoidosis, rather than panic disorder. CONCLUSIONS: This report highlights the importance of considering cardiac sarcoidosis in the differential diagnosis of panic disorder. This cardiac disease should be considered especially in patients have a history of cardiac disease (e.g., arrhythmia) and atypical presentations of panic symptoms. Panic disorder is a psychiatric condition that is typically diagnosed after other medical conditions have been excluded. Because the diagnosis of sarcoidosis is difficult in some patients, caution is required. The palpitations and symptoms of heart failure associated with cardiac sarcoidosis can be misdiagnosed as psychiatric symptoms of panic disorder. The condition described in the current case study appears to constitute a physical disease, the diagnosis of which requires significant consideration and caution.

Rescue balloon pulmonary angioplasty in a rapidly deteriorating chronic thromboembolic pulmonary hypertension patient with liver failure and refractory infection.

Pulmonary endarterectomy (PEA) is the standard therapy for chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) is an alternative therapy for such patients. Here we report the case of a 60-year-old woman who presented with severe CTEPH resulting in low cardiac output and liver failure. Her clinical status rapidly deteriorated after she developed a respiratory infection that was refractory to antibiotic treatment. PEA was risky because of her unstable hemodynamics, uncontrolled infection, and liver failure with jaundice. We thus performed rescue BPA. After 3 BPA procedures, her cardiac symptoms improved from World Health Organization functional class IV to II, and her jaundice resolved. The day after her final BPA procedure, her hemodynamics dramatically improved, and she continued to show improvement 3 months later. We thus suggest that BPA is a good treatment option in CTEPH patients with rapidly deteriorating heart failure and uncontrolled comorbidities.

Organized thrombus in pulmonary arteries in patients with chronic thromboembolic pulmonary hypertension; imaging with cone beam computed tomography.

PURPOSE: To assess the usefulness of cone-beam CT (CBCT) during pulmonary angiography for the evaluation of organized thrombus at segmental or subsegmental arteries in patients with chronic thromboembolic pulmonary hypertension (CTEPH). MATERIALS AND METHODS: The segmental and/or subsegmental pulmonary arteries of 13 patients with CTEPH were evaluated by CBCT. We classified representative forms of organized thrombus into 4 types (type 1: webs, type 2: web and slits, type 3: slits, and type 4: narrowing or complete occlusion), and the distribution and frequency of the organized thrombus were evaluated. The relative detectability of these lesions using CBCT was compared with that in contrast-enhanced CT pulmonary angiography (CTPA). RESULTS: Type 1 lesions were most frequently observed in both segmental (30/65 = 46 %) and subsegmental branches (72/156 = 46 %). Type 2 lesions were relatively less frequent than type 1, but subsegmental branches were frequently involved (29/156 = 19 %). Type 3 lesions observed as a thin flap in 9/156 subsegmental branches (6 %). Comparing with CTPA, all 40 lesions in segmental branches were detectable in CTPA, whereas only 62 lesions among 90 lesions (69 %) in subsegmental branches could be observed by CTPA. CONCLUSION: CBCT is found to be useful for the treatment planning of balloon pulmonary angioplasty distal to segmental arteries.

Acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, in patients with pulmonary arterial hypertension.

We have previously demonstrated that long-term inhibition of Rho-kinase ameliorates pulmonary arterial hypertension (PAH) in animal models. In the present study, we examined acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, as a more feasible option to locally deliver the drug for PAH. We examined 15 patients with PAH (13 women and 2 men, 45 +/- 4 years old), including idiopathic PAH (n = 5), PAH associated with connective tissue disease (n = 6), PAH with congenital heart disease (n = 3), and portal PAH (n = 1). In those patients, we performed right heart catheterization with a Swan-Ganz catheter in the two protocols with inhalation of nitric oxide (NO) (40 ppm, 10 min) and fasudil (30 mg, 10 min) with a sufficient interval (>30 min). Both NO and fasudil inhalation significantly reduced mean pulmonary arterial pressure (PAP) (NO: P < 0.01, fasudil: P < 0.05) and tended to decrease pulmonary vascular resistance (NO: P = 0.07, fasudil: P = 0.1), but did not affect cardiac index. The ratio of pulmonary to systemic vascular resistance was significantly reduced both in NO and fasudil inhalation (NO: P < 0.01, fasudil: P < 0.05), indicating that both NO and fasudil inhalation selectively affect lung tissues. Interestingly, there was no correlation in the vasodilator effects between NO and fasudil, and a positive correlation with serum levels of high-sensitivity C-reactive protein was noted for fasudil but not for NO. These results suggest that inhalation of fasudil is as effective as NO in patients with PAH, possibly through different mechanisms.

Long-term epoprostenol therapy in pulmonary artery hypertension.

BACKGROUND: Sequential changes in the hemodynamic effect of chronic epoprostenol therapy raise the following questions. Does an increase in cardiac output (CO) precede lowering of the pulmonary artery pressure (PAP) over the time course of improvement? What are the characteristics of good responders to chronic epoprostenol treatment? METHODS AND RESULTS: Hemodynamics were evaluated by catheter examination. Most patients still alive after >1 year showed an increase in CO either with no change in mean PAP or accompanied by a decrease in mean PAP during increased dosing of epoprostenol. Immediately before cessation of the increase in epoprostenol dose in good responders, the ratio of total pulmonary resistance to total systemic resistance was low, and the pulmonary artery wedge pressure minus right atrial pressure was high compared with the newest data in poor responders. One year after fixing at the best dose of epoprostenol, the mean PAP further decreased. CONCLUSIONS: In good responders, pulmonary selectivity to epoprostenol is high, and the blood returning to the left-sided heart through the pulmonary circulation increases. Hemodynamics further improve, even after fixing at the best dose of epoprostenol. The present data did not show that an increase in CO precedes lowering of the PAP over the course of improvement.

Statin ameliorates hypoxia-induced pulmonary hypertension associated with down-regulated stromal cell-derived factor-1.

AIMS: Mobilization of stem cells/progenitors is regulated by the interaction between stromal cell-derived factor-1 (SDF-1) and its ligand, CXC chemokine receptor 4 (CXCR4). Statins have been suggested to ameliorate pulmonary arterial hypertension (PAH); however, the mechanisms involved, especially their effects on progenitors, are largely unknown. Therefore, we examined whether pravastatin ameliorates hypoxia-induced PAH in mice, and if so, which type of progenitors and what mechanism(s) are involved. METHODS AND RESULTS: Chronic hypoxia (10% O(2) for 5 weeks) increased the plasma levels of SDF-1 and mobilization of CXCR4(+)/vascular endothelial growth factor receptor (VEGFR)2(+)/c-kit(+) cells from bone marrow (BM) to pulmonary artery adventitia in Balb/c mice in vivo, both of which were significantly suppressed by simultaneous oral treatment with pravastatin (2 mg/kg/day). Furthermore, in vitro experiments demonstrated that hypoxia enhances differentiation of VEGFR2(+)/c-kit(+) cells into alpha-smooth muscle actin(+) cells. Importantly, pravastatin ameliorated hypoxia-induced PAH associated with a decrease in the number of BM-derived progenitors accumulating in the pulmonary artery adventitia. The expression of intercellular adhesion molecule-1 (ICAM-1) and its ligand, CD18 (beta2-integrin), were enhanced by hypoxia and were again suppressed by pravastatin. CONCLUSIONS: These results suggest that pravastatin ameliorates hypoxia-induced PAH through suppression of SDF-1/CXCR4 and ICAM-1/CD18 pathways with a resultant reduction in the mobilization and homing of BM-derived progenitor cells.

Epoprostenol infusion therapy changes angiographic findings of pulmonary arteries in patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: The pulmonary vascular changes induced by epoprostenol in patients with idiopathic pulmonary artery hypertension (IPAH) have not been reported by a clinical study. METHODS AND RESULTS: Analysis 1 compared the wedged pulmonary angiography (PAG) findings prior to initiation of epoprostenol therapy (n=24) with those after initiation (n=16). Analysis 2 compared the PAG findings prior to and after initiation of epoprostenol therapy (n=9) in the same pulmonary arteries in the same subjects. In analysis 1, a "cotton grass-like" stain originating from the peripheral pulmonary vessels (each vessel could not be distinguished on angiography) was not observable in any of 24 cases before initiation of epoprostenol therapy, but was visible in 13 of 16 cases after (p<0.0001). In analysis 2, the diameter of subsegmental arteries changed from 3.0+/-0.9 mm (mean +/- standard deviation) to 3.7+/-1.2 mm (p=0.004) between the 2 time periods. Cotton grass-like stain was not found in any cases before epoprostenol, but in all 9 cases after chronic use (p=0.004). CONCLUSIONS: After initiating epoprostenol therapy, cotton grass-like stain appeared in most patients with IPAH. The possible reason for this is release of severe vasoconstriction and/or emergence of neovascularization.

Proximal pulmonary artery aneurysms in patients with pulmonary artery hypertension: complicated cases.

Cases with proximal pulmonary artery aneurysm (PAA) sometimes have severe complications. We report 4 cases of proximal PAA complicated by pulmonary hypertension. Three cases had proximal PAA and one had both proximal and peripheral PAA. Complications associated with proximal PAA are compression of the bronchus, dissection and/or rupture of the pulmonary artery, and thrombus of the pulmonary artery. The available medical treatments have limitations. Two of our patients with proximal PAA are awaiting lung transplantation.

Peripheral pulmonary artery aneurysms in patients with pulmonary artery hypertension.

Pulmonary artery aneurysm (PAA), especially the peripheral type, is a rare disease. We report 2 cases of peripheral PAA with pulmonary artery hypertension. Complication associated with peripheral PAA was hemoptysis. Endovascular coil embolization was performed successfully in one patient. The other with peripheral PAA was died of massive hemoptysis. In patients with peripheral PAA, coil embolization is one therapeutic option. We summarized cases with peripheral PAA in Japan.

Portopulmonary hypertension: hemodynamics, pulmonary angiography, and configuration of the heart.

BACKGROUND: The goal of the present study was to examine the cardiac configuration and pulmonary vascular changes in patients with portopulmonary hypertension (PPHTN) and compare them with those of idiopathic pulmonary arterial hypertension (IPAH). METHODS AND RESULTS: The subjects were 10 patients with PPHTN and 18 with IPAH. In PPHTN, the increases in the right ventricular end-diastolic volume index (89+/-19 vs 128+/-50 ml/m2; p=0.04), right end-systolic volume index (50+/-19 vs 95+/-47 ml/m 2; p=0.02) and right ventricular mass index (47+/-18 g/m2 vs 79+/-31; p=0.04) were low compared with IPAH. The decrease in the right ventricular ejection fraction was also low in PPHTN (45+/-10 vs 28+/-13%; p=0.01). The degree of sparse arborization and abrupt narrowing on wedged pulmonary angiography was moderate in PPHTN compared with IPAH. In PPHTN, the proximal pulmonary arteries were dilated near the segmental arteries, which were narrow in IPAH. CONCLUSION: Changes in the configuration of the heart were moderate in PPHTN compared with those in IPAH. The degree of sparse arborization and abrupt narrowing were also moderate in PPHTN.

Increased [18F]fluorodeoxyglucose accumulation in right ventricular free wall in patients with pulmonary hypertension and the effect of epoprostenol.

OBJECTIVES: We examined whether right ventricular (RV) [(18)F]fluorodeoxyglucose (FDG) accumulation is increased in patients with pulmonary hypertension using gated positron emission tomography (PET) and whether RV FDG accumulation changes after therapy with epoprostenol. BACKGROUND: Myocardial glucose utilization is increased in animal models with ventricular pressure overload. METHODS: We performed gated FDG-PET in 24 patients with pulmonary hypertension. The RV standardized uptake value (SUV) of FDG was corrected for the partial volume effect based on the wall thickness measured by electron-beam computed tomography or magnetic resonance imaging. RESULTS: The corrected RV SUV of FDG was significantly correlated with the pulmonary vascular resistance, mean pulmonary artery pressure, right atrial pressure, RV wall stress, and plasma brain natriuretic peptide levels, but not with the RV wall thickness and mass. After pulmonary vasodilator therapy with epoprostenol for three months, the corrected RV SUV of FDG significantly decreased in the responders, but not in the non-responders, and the percentage change of the corrected RV SUV of FDG was significantly correlated with the percentage change of the pulmonary vascular resistance (r = 0.78; p < 0.01) and RV systolic wall stress (r = 0.76; p < 0.05). CONCLUSIONS: The RV FDG accumulation corrected for the partial volume effect was significantly increased in accordance with the severity of the RV pressure overload (i.e., the RV peak-systolic wall stress) in patients with pulmonary hypertension. Furthermore, the corrected RV FDG accumulation was decreased after the treatment with epoprostenol in accordance with the degree of reduction in the pulmonary vascular resistance and RV peak-systolic wall stress.

Efficacy of acute inhalation of nitric oxide in patients with primary pulmonary hypertension using chronic use of continuous epoprostenol infusion.

BACKGROUND: There have only been a few reports published on combination therapy for patients with primary pulmonary hypertension (PPH). METHODS AND RESULTS: Fifteen patients with PPH (4 men and 11 women, 34.5+/-12.1 years old) had received chronic administration of epoprostenol and the additive effects of inhaled nitric oxide (NO) and the hemodynamic changes were evaluated. In addition, the difference in the effect of acute NO loading before and after the epoprostenol therapy was compared in 6 of these patients. Under chronic use of epoprostenol, mean pulmonary arterial pressure, mean right atrial pressure and pulmonary vascular resistance were decreased with acute inhalation of NO. However, cardiac output, mean aortic pressure and systemic vascular resistance were unchanged. As a result, the pulmonary to systemic vascular resistance ratio was reduced. Moreover, after chronic use of epoprostenol, the change (delta) in cardiac output with NO inhalation was increased and the NO-induced decrease in pulmonary vascular resistance was augmented compared to those before the induction. CONCLUSION: Nitric oxide inhalation further improved the hemodynamics when combined with chronic use of epoprostenol in PPH patients. These results suggest the possibility that combination therapies can be used in the treatment for PPH patients.

Characteristics of the increase in plasma brain natriuretic peptide level in left ventricular systolic dysfunction, associated with muscular dystrophy in comparison with idiopathic dilated cardiomyopathy.

To determine whether the plasma brain natriuretic peptide level increases differentially in muscular dystrophy and idiopathic dilated cardiomyopathy, we investigated the plasma brain natriuretic peptide level and echocardiographic parameters in patients with similarly low left ventricular ejection fraction. The plasma brain natriuretic peptide level was lower, and the left ventricular end-diastolic diameter was shorter in the patients with muscular dystrophy than in those with idiopathic dilated cardiomyopathy. The correlation between the plasma brain natriuretic peptide and left ventricular ejection fraction was shifted downward in the patients with muscular dystrophy compared with those with idiopathic dilated cardiomyopathy. Those between the brain natriuretic peptide and left ventricular end-diastolic diameter were superimposable, although the data from the muscular dystrophy patients were located at the shorter left ventricular end-diastolic diameter side. The plasma brain natriuretic peptide level may differentially increase in the two diseases with similar left ventricular systolic dysfunction. Differences in the left ventricular distension and in the physical activity might explain at least partially the different plasma brain natriuretic peptide levels.

Effects and problems of continuous infusion of epoprostenol for patients with primary pulmonary hypertension.

OBJECTIVE: We examined the usefulness and the problems of epoprostenol (Epo) therapy in adult Japanese with primary pulmonary hypertension (PPH). SUBJECTS AND METHODS: In eleven cases with PPH, both acute and chronic effects, and clinical effects of Epo were assessed. RESULTS: In the acute challenge test (n = 6), Epo reduced both systemic and pulmonary vascular resistance and increased the cardiac output, but did not change the ratio of pulmonary to systemic vascular resistance, while the systemic and pulmonary blood pressure also did not change. In the chronic study (n = 9), Epo decreased the pulmonary blood pressure without changes in systemic blood pressure, and increased the cardiac output. Both systemic and pulmonary vascular resistance decreased with a decrease in the ratio of the pulmonary to systemic vascular resistance. The level of brain natriuretic peptide and atrial natriuretic peptide, NYHA functional class and 6-minute walking distance were improved by Epo therapy. In spite of Epo therapy, two patients did not improve and died. Another patient improved in terms of symptoms but then died suddenly from massive lung bleeding. Two patients who improved physically could not be discharged because of psychiatric problems. One patient underwent lung transplantation. Five out-patients have been continuing Epo therapy. CONCLUSION: We demonstrated that the chronic effect of Epo treatment is sufficient even at the dose used in our hospital. However, it was shown that there was resistance to this therapy in some of the cases and that we should pay attention to the severe adverse effects of Epo.