Diagnosis and Detection of Myocardial Injury in Active Cardiac Sarcoidosis--Significance of Myocardial Fatty Acid Metabolism and Myocardial Perfusion Mismatch.

BACKGROUND: Myocardial injury can be detected more sensitively using (123)I-radioiodinated 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid (BMIPP) than thallium-201 (TL). The present study investigated whether (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) uptake as an index of active inflammation in patients with cardiac sarcoidosis (CS) is associated with BMIPP and TL findings, and whether dual single-photon emission computed tomography (SPECT) can facilitate diagnosis of CS. METHODS AND RESULTS: We retrospectively enrolled 52 consecutive patients with suspected CS who were assessed on FDG-PET/computed tomography (CT) and BMIPP/TL dual SPECT. The SPECT images were divided into 17 segments and then BMIPP and TL total defect scores (BMDS, TLDS) as well as mismatch scores (BMDS-TLDS: sumMS) were calculated. Maximum standardized uptake value (SUVmax) in the entire myocardium was obtained from FDG-PET/CT. SUVmax was much higher in patients with, than without CS (P<0.0001). BMDS was higher and sumMS much higher in CS (P<0.05 and P<0.0001, respectively). The sensitivity and specificity of sumMS to detect CS were 74% and 80%, respectively. SUVmax was not associated with either BMDS or sumMS in the patients with CS. On multivariate analysis, the combination of sumMS and SUVmax had greater prognostic significance compared with each parameter on its own. CONCLUSIONS: BMIPP and TL dual-tracer mismatch is a useful finding to diagnose CS, and adds greater diagnostic value to SUVmax on FDG-PET/CT.

Differences in hemodynamic responses between intravenous carperitide and nicorandil in patients with acute heart failure syndromes.

While recent guidelines for the treatment of acute heart failure syndromes (AHFS) recommend pharmacotherapy with vasodilators in patients without excessively low blood pressure (BP), few reports have compared the relative efficiency of vasodilators on hemodynamics in AHFS patients. The present study aimed to assess the differences in hemodynamic responses between intravenous carperitide and nicorandil in patients with AHFS. Thirty-eight consecutive patients were assigned to receive 48-h continuous infusion of carperitide (n = 19; 0.0125-0.05 µg/kg/min) or nicorandil (n = 19; 0.05-0.2 mg/kg/h). Hemodynamic parameters were estimated at baseline, and 2, 24, and 48 h after drug administration using echocardiography. After 48 h of infusion, systolic BP was significantly more decreased in the carperitide group compared with that in the nicorandil group (22.1 ± 20.0 % vs 5.3 ± 10.4 %, P = 0.003). While both carperitide and nicorandil significantly improved hemodynamic parameters, improvement of estimated pulmonary capillary wedge pressure was greater in the carperitide group (38.2 ± 14.5 % vs 26.5 ± 18.3 %, P = 0.036), and improvement of estimated cardiac output was superior in the nicorandil group (52.1 ± 33.5 % vs 11.4 ± 36.9 %, P = 0.001). Urine output for 48 h was greater in the carperitide group, but not to a statistically significant degree (4203 ± 1542 vs 3627 ± 1074 ml, P = 0.189). Carperitide and nicorandil were differentially effective in improving hemodynamics in AHFS patients. This knowledge may enable physicians in emergency wards to treat and manage patients with AHFS more effectively and safely.

Systemic sclerosis complicated by chronic thromboembolic pulmonary hypertension treated with balloon pulmonary angioplasty: a case report.

BACKGROUND: Systemic sclerosis (SSc) is known to induce pulmonary hypertension (PH), resulting in poor prognosis. Pulmonary hypertension secondary to connective tissue disease is usually classified as Group 1. In patients with SSc, PH owing to left heart failure (Group 2) and interstitial pneumonia (Group 3) are also known; however, there have been limited reports on chronic thromboembolic PH (CTEPH), which corresponds to Group 4. CASE SUMMARY: A 39-year-old female with SSc was admitted with shortness of breath on exertion for the past 4 months. Right heart catheterization revealed severe PH. Group 1 PH secondary to collagen tissue disease was suspected; however, thoracic computed tomography and lung perfusion scan led to the diagnosis of CTEPH of Group 4. We treated the PH with several medications and balloon pulmonary angioplasty (BPA), which improved the PH and right heart failure. Consequently, her overall condition also improved. DISCUSSION: This is a rare case report of SSc complicated by CTEPH, which was treated with BPA. Patients with SSc are prone to complications of various type of PH. Thus, it is important to distinguish CTEPH in terms of treatment choice and prognosis.

A novel optimized adaptive servo-ventilation setting for a patient with severe heart failure based on the echocardiogram: a case report.

Background: Adaptive servo-ventilation (ASV) is a non-invasive positive-pressure ventilation therapy considered beneficial for treating heart failure (HF) in patients with central sleep apnoea. However, to the best of our knowledge, there is no evidence indicating that this therapy increases the mortality in HF patients. We hypothesized that ASV settings are important for HF patients with reduced ejection fraction. Therefore, to determine the suitable ASV setting for such patients, we optimized these settings to improve the left ventricular (LV) output during the therapy. Case summary: We present a case of HF caused by dilated cardiomyopathy in a 45-year-old man. He was hospitalized due to HF; his LV ejection fraction was ∼20%, and haemodynamics analysis revealed his HF grade was Forrester subset IV. During hospitalization, he was diagnosed with sleep apnoea; therefore, we induced ASV with our optimized setting using an echocardiogram evaluating stroke volume (SV). Using this method, we could determine the appropriate setting that increased his SV and improved his apnoea-hypopnoea index. At the 5th-year follow-up, he had no dyspnoea on effort (New York Heart Association Functional Classification I). He continued using the ASV with good adherence, and no hospitalization for ventricular arrhythmia and HF was reported. Discussion: Our ASV optimized setting showed beneficial effects in an HF patient with reduced ejection fraction. This method improved the patient's SV and apnoea-hypopnoea index, indicating that this novel method should be considered for HF patients with reduced ejection fraction.

Discrepancy between significant fibrosis and active inflammation in patients with cardiac sarcoidosis: combined and image fusion analysis of cardiac magnetic resonance and 18F fluorodeoxyglucose positron emission tomography.

BACKGROUND: Diagnosis and evaluation of cardiac sarcoidosis (CS) are mainly based on the combined use of cardiac magnetic resonance imaging (CMR) and 18F fludeoxyglucose positron emission tomography (FDG). Though these modalities can detect the pathological feature of the disease, combined assessment has not been fully examined. Multimodality image fusion is known to be useful for further comprehension, while most image interpretation is performed with a side by side comparison in clinical routine. We investigated the similarity and discrepancy of active inflammation, regional fibrosis, and wall function by image fusion of CMR and FDG. METHODS: Patients with CS who underwent both CMR and FDG were retrospectively enrolled. The extent of myocardial late gadolinium enhancement (LGE) in left ventricle (LGE volume), cardiac function, and volume (left ventricular ejection fraction, LVEF; end-diastolic volume, EDV) was measured from CMR. The FDG uptake in whole myocardium (whole SUVmax), cardiac metabolic volume (CMV), and cardiac metabolic activity (CMA) was calculated from FDG. CMR and FDG were fused and divided into AHA 17 model for segmental analysis. Wall motion, the magnitude of LGE in myocardial wall (LGE%wall), and corresponding FDG uptake (segmental SUVmax) were analyzed. RESULTS: Forty-one patients were retrospectively enrolled. In patients with FDG uptake, LVEF inversely correlated to LGE volume and positively correlated to SUVmax (r = - 0.56, p < 0.0001, and r = 0.08, p = 0.048, respectively). Discrepancy between LGE volume and CMV showed a significant positive correlation to whole SUVmax and CMA (r = 0.49, p < 0.0001, and r = 0.96, p < 0.0001, respectively). In image fusion analysis, segmental SUVmax showed a significant inverse correlation to LGE%wall (Spearman's rank correlation coefficient; r = - 0.15, p = 0.008). LGE%wall also showed significant inverse correlation to wall motion (r = - 0.13, p = 0.0011). CONCLUSION: Combined and fusion analysis with CMR and FDG demonstrated the discrepancy of myocardial inflammation and extensive fibrosis. Active inflammation was present in the earlier stage of myocardial fibrosis and was found to be less in the wall with advanced fibrosis and remodeling. Combined analysis of CMR and FDG can incrementally reclassify the pathological stage of CS.

A case of desmoplakin mutation and delayed arrhythmogenic right ventricular cardiomyopathy/dysplasia after atrial septal defect closure.

Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a slow-developing cardiomyopathy characterized by ventricular arrhythmias and fibrofatty replacement of the right ventricular (RV) myocardium. Its clinical diagnosis is challenging because of its variable clinical presentation and low genetic penetrance. We describe the case of a 67-year-old man who was diagnosed as having ARVC/D with a desmoplakin mutation that appeared after occlusion of an atrial septal defect (ASD). He underwent patch closure surgery for ASD at the age of 54 years. Four years later, he underwent catheter ablation for multifocal atrial tachycardias. Because of pre-syncope and inducible sustained monomorphic ventricular tachycardia, an implantable cardioverter defibrillator was implanted. When he was admitted for worsening heart failure at the age of 61 years, the desmoplakin mutation was detected with progressive left ventricular (LV) dysfunction. Subsequently, he was diagnosed as having ARVC/D with RV dysfunction. At cardiac autopsy, characteristics of ARVC/D, including dilatation, fibrofatty changes in the right ventricle, and diffuse fibrosis in the left ventricle were detected. Along with the effect of RV dysfunction caused by ASD, the progression of LV dysfunction after ASD closure was also possibly caused by the disease progression of ARVC/D. Physicians should carefully assess the various states of ARVC/D. .

Successfully treated eosinophilic granulomatosis with polyangiitis relapse presenting as myocarditis and followed by multimodality imaging.

A 60-year-old man with eosinophilic granulomatosis with polyangiitis (EGPA), which was diagnosed 12 years earlier and managed with prednisolone, was admitted to our hospital because of dyspnea and paresthesias in both hands. Laboratory test revealed peripheral eosinophilia along with elevated troponin T and brain natriuretic peptide (BNP). The patient's clinical picture was consistent with myocarditis and relapse of EGPA. Endomyocardial biopsy showed marked infiltration of eosinophils in myocardium, which confirmed relapse of EGPA with myocarditis. Thallium-201 and iodine-123-beta-methyl iodophenyl pentadecanoic acid dual single-photon emission computed tomography (TL-BMIPP SPECT), as well as cardiac magnetic resonance imaging (CMR), also confirmed cardiac involvement. The patient was treated with methylprednisolone and improved dramatically. CMR and TL-BMIPP SPECT performed after discharge showed improvement of abnormal lesions, while anomalies detected by these modalities remained. This is a case of EGPA relapse presenting as myocarditis despite treatment with prednisolone. .

Effect of Balloon Pulmonary Angioplasty on Respiratory Function in Patients With Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Balloon pulmonary angioplasty (BPA) in chronic thromboembolic pulmonary hypertension (CTEPH) improves hemodynamics and exercise capacity. However, its effect on respiratory function is unclear. Our objective was to investigate the effect of BPA on respiratory function. METHODS: We enrolled patients with inoperable CTEPH who underwent BPA primarily in lower lobe arteries (first series) and upper and middle lobe arteries (second series). We compared changes in hemodynamics and respiratory function between different BPA fields. RESULTS: Sixty-two BPA sessions were performed in 13 consecutive patients. Mean pulmonary arterial pressure and pulmonary vascular resistance significantly improved from 44 ± 8 to 23 ± 5 mm Hg and 818 ± 383 to 311 ± 117 dyne/s/cm-5. The percent predicted diffusion capacity of lung for carbon monoxide (Dlco) decreased after BPA in the lower lung field (from 60% ± 8% to 54% ± 8%) with no recovery. Percent Dlco increased after BPA in the upper middle lung field (from 53% ± 6% to 58% ± 6%) and continued to improve during the follow-up (from 58% ± 6% to 64% ± 11%). The ventilation/Co2 production (V˙e/V˙co2) slope significantly improved after BPA in the lower lung field (from 51 ± 13 to 41 ± 8) and continued to improve during the follow-up (from 41 ± 8 to 35 ± 7); however, the V˙e/V˙co2 slope remained unchanged after BPA in the upper/middle lung field. Changes in % Dlco and the V˙e/V˙co2 slope differed significantly between lower and upper/middle lung fields. CONCLUSIONS: The effect of BPA on respiratory function in patients with CTEPH differed depending on the lung field.

Regional myocardial damage and active inflammation in patients with cardiac sarcoidosis detected by non-invasive multi-modal imaging.

AIMS: Cardiac sarcoidosis (CS) can be diagnosed using 18F-FDG-PET/CT (PET), cardiovascular magnetic resonance (CMR), and 123I-BMIPP/201TlCl dual myocardial SPECT. This study aims to clarify the relationships among the three modalities with respect to CS. METHODS AND RESULTS: We evaluated 16 patients (male n = 11; age 55 ± 13 years) with confirmed CS who underwent PET, CMR, and dual SPECT with gated SPECT before starting steroid therapy. The left ventricular myocardium was divided into 17 segments to obtain SUVmax for PET images, defect scores from 0 to 4 (0 normal; 4 absent), and mismatch scores for dual SPECT (BMDS, TLDS, and MS) images and late gadolinium enhancement (LGE) scores (0 none; 1 partly positive; 2 homogeneous) on CMR images. Summed BMDS, TLDS, and MS were 18.6 ± 12.6, 12.9 ± 10.9, and 5.7 ± 3.1, respectively. The segmental BMDS and TLDS scores became significantly higher as the LGE scores increased. The MS scores were significantly higher in areas of LGE with a score of 1 than 0 (both, p < 0.001), but did not significantly differ between areas with LGE scores of 1 and 2. The SUVmax was significantly higher in LGE areas with a score of 1 than 0 (p < 0.025), but did not significantly differ between those with scores of 1 or 2. CONCLUSION: Regions with a higher SUVmax indicating active myocardial inflammation were mainly located in areas with LGE, where BMIPP and TL mismatches were evident in patients with CS.

An overlap of Brugada syndrome and arrhythmogenic right ventricular cardiomyopathy/dysplasia.

Overlapping characteristics of Brugada syndrome (BrS) and arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) have been reported in recent studies, but little is known about the overlapping disease state of BrS and ARVC/D. A 36-year-old man, hospitalized at our institution for syncope, presented with this overlapping disease state. The electrocardiogram showed spontaneous coved-type ST-segment elevation, and ventricular fibrillation was induced by right ventricular outflow tract stimulation in an electrophysiological study. BrS was subsequently diagnosed; additionally, the presence of epsilon-like waves and right ventricular structural abnormalities met with the 2010 revised task force criteria for ARVC/D. After careful investigation for both BrS and ARVC/D, an implantable cardioverter defibrillator was inserted in the patient. This case revealed 2 important clinical findings: (1) BrS and ARVC/D clinical features can coexist in a single patient, and EPS might be useful for determining the phenotype of overlapping disease (e.g., BrS-like or ARVC/D-like). (2) An overlapping disease state of BrS and ARVC/D can change phenotypically during its clinical course. Therefore, careful examination and attentive follow-up are required for patients with BrS or ARVC/D.

Cardiac Sarcoidosis Masked by Malignant Lymphoma.

There is an association between sarcoidosis and lymphoma, termed "sarcoidosis-lymphoma syndrome." Sarcoidosis is generally detected before lymphoma, but it could present after or even concurrently with the diagnosis of lymphoma. We describe a patient presenting with ventricular tachycardia and lymphadenopathy. A diagnosis of Hodgkin lymphoma was made histologically. The patient responded to treatment, but had persistent (18)F-fluoro-deoxyglucose uptake in the lymph nodes and heart on follow-up positron emission tomography. Second biopsies of lymph node and endomyocardial both confirmed sarcoidosis. This finding suggests that we should maintain a high degree of suspicion for cardiac sarcoidosis in lymphoma patients.

Isolated cardiac sarcoidosis diagnosed by electroanatomic voltage mapping-guided endomyocardial biopsy combined with magnetic resonance imaging and positron emission tomography.

Cardiac involvement in sarcoidosis is related to lethal arrhythmias and is considered a serious condition. Because steroid therapy is an effective treatment, early diagnosis of cardiac sarcoidosis (CS) is of paramount importance in respect to improving prognosis. However, the diagnostic yield of histologic examination by endomyocardial biopsy (EMB) in CS is usually low. We report the case of isolated CS histopathologically proven by electroanatomical voltage mapping (EVM)-guided EMB combined with cardiac magnetic resonance imaging (CMR) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). A 53-year-old man presented with general fatigue. Electrocardiography showed intermittent complete atrioventricular block and echocardiography showed reduced cardiac function. CMR showed late gadolinium enhancement (LGE) in the areas of myocardium with suspected sarcoidosis. Next, we performed an EVM-guided EMB and found a non-caseating epithelioid granuloma in the right ventricular septum, which showed low voltage on EVM and LGE on CMR. FDG-PET showed accumulation in the same cardiac region. This case shows that EVM-guided EMB combined with diagnostic imaging can be a valuable approach in cases of suspected isolated CS. .

Combination therapy with corticosteroid and mycophenolate mofetil in a case of refractory cardiac sarcoidosis.

Management of cardiac sarcoidosis (CS) can be challenging. The first-line therapy for this condition is corticosteroids, but other immunosuppressive agents are sometimes co-administered to reduce the dosage of corticosteroid and to thereby avoid steroid-induced adverse effects or to increase its therapeutic efficacy. Mycophenolate mofetil (MMF) is a prodrug of mycophenolic acid, an inhibitor of inosine monophosphate dehydrogenase that acts more selectively on T and B lymphocytes when compared with azathioprine. A 40-year-old man was diagnosed with CS after presenting with ventricular fibrillation. His left ventricular ejection fraction was severely reduced (30%), and cardiac positron emission tomography (PET) showed abnormal uptake of 18F-fluorodeoxyglucose. A cardioverter-defibrillator was implanted and prednisolone (30 mg/day) was administered. He was re-admitted with recurrent sustained ventricular tachycardia and a positive PET finding despite a 5-month course of prednisolone, and MMF (1000 mg/day) was administered. Six months later, he had not required re-hospitalization for heart failure or arrhythmia. We conclude that combination therapy with MMF and corticosteroids is useful for refractory CS. .

Percutaneous coronary intervention for left main compression syndrome due to severe idiopathic pulmonary arterial hypertension: one year follow-up using intravascular imaging.

A 60-year-old woman presented with ST-elevation myocardial infarction due to extrinsic compression of the left main coronary artery (LMCA) caused by a dilated pulmonary artery (PA) with idiopathic pulmonary hypertension and was successfully treated with intravascular ultrasound- and optical coherence tomography-guided stenting. Continuous subcutaneous epoprostenol infusion therapy was initiated immediately after the procedure and increased aggressively. Imaging modalities were extremely useful in making the diagnosis and providing follow-up of LMCA compression syndrome in this case. Over the one-year observation period, a sufficient hemodynamic improvement was obtained, without exacerbation of the PA dilatation, resulting in the absence of compression of the LMCA.

Association between sleep apnea and overnight hemodynamic changes in hospitalized heart failure patients with and without paroxysmal nocturnal dyspnea.

BACKGROUND: Paroxysmal nocturnal dyspnea (PND) is a common symptom for patients with acute decompensated heart failure (ADHF). Some symptoms of PND are similar to those of sleep apnea (SA) which might be associated with overnight worsening hemodynamics in failing hearts. However, the association between PND, SA, and overnight change in hemodynamics in patients with heart failure remains uncertain. METHODS: We studied 28 consecutive patients with reduced ejection fraction who were hospitalized with ADHF. Plasma atrial natriuretic peptide (ANP) levels were measured before and after overnight sleep study. PND was defined as having an episode of PND prior to hospitalization for ADHF. RESULTS: Ten (36%) patients had a history of PND. Respiratory disturbance index (the frequency and severity of sleep apnea) was an independent factor associated with a history of PND (odds ratio 1.24, 95% confidence interval 1.05-1.47, p=0.011). In those without PND, plasma ANP levels decreased from before sleep to after waking, whereas in those with PND it increased (p=0.011). In addition, overnight change in plasma ANP levels was independently associated with respiratory disturbance index (p=0.035). CONCLUSION: These results thus suggest that in patients with ADHF, SA might be a predisposing cause of PND in association with overnight worsening hemodynamics.

Impact of sleep-disordered breathing on life-threatening ventricular arrhythmia in heart failure patients with implantable cardioverter-defibrillator.

It was recognized that sleep-disordered breathing (SDB) is associated with cardiac arrhythmia and sudden cardiac death. However, it was unclear whether the presence of SDB increased the risk of life-threatening ventricular arrhythmia in patients with heart failure (HF) with an implantable cardioverter-defibrillator (ICD). Seventy-one patients with HF and an ICD who were followed up for 180 days after a sleep study were prospectively studied. All patients had an ejection fraction or=10 events/hour on the sleep study. The frequency of appropriate ICD therapy and the day-night pattern of ICD therapies were compared between patients with and without SDB. SDB was diagnosed in 47 of 71 patients (66%). There were no statistical differences between patients with and without SDB in baseline cardiac function. However, appropriate ICD therapies occurred more frequently in patients with (43%) than without SDB (17%; p = 0.029). On multivariate analysis, the presence of SDB was an independent predictor for appropriate ICD therapy (hazard ratio 4.05, 95% confidence interval 1.20 to 13.65, p = 0.015). Moreover, the rate of total ICD therapy from midnight to 6 A.M. was significantly higher in patients with (34%) than without SDB (13%; p = 0.046). In conclusion, in patients with HF with an ICD, the presence of SDB was common and an independent predictor of life-threatening ventricular arrhythmias that were more likely to occur during sleep.