Clinical Characteristics of Cryoglobulinemia With Cardiac Involvement in a Single Center

Background: Cryoglobulinemia is a syndrome characterized by the presence of cryoglobulins (CGs) in serum, and cardiac involvement is a rare occurrence that can affect treatment and prognosis. This study aimed to explore the clinical characteristics of cryoglobulinemia with cardiac involvement.Methods: 108 patients diagnosed with cryoglobulinemia who were admitted and treated in Peking Union Medical College Hospital (PUMCH) between June 1985 and June 2019 were enrolled in the present study. Clinical characteristics, therapy, and prognosis of patients with cardiac involvement were retrospectively analyzed.Results: The cryoglobulinemia with cardiac involvement was found in 7 patients, thus reaching the incidence of 6.5%. Heart failure was the main cardiac manifestation found in these patients, all with the involvement of external cardiac organs. Laboratory examinations showed significant elevation of N-terminal brain natriuretic peptide precursor (NT-proBNP) and brain natriuretic peptide (BNP) with negative troponin (cTnI). Electrocardiogram (ECG) was generally normal or only showed low-flat and biphasic multi-lead T waves. Echocardiography was performed in 6 patients, all of whom showed enlargement of heart cavity. Five patients had reduced left ventricular myocardial contractible motion with decreased ejection fraction, 3 patients had pericardial effusion, and 1 patient had left ventricular hypertrophy or severe aortic insufficiency. Cardiac magnetic resonance imaging showed delayed myocardial enhancement in 2 patients. One patient underwent a myocardial biopsy, which showed perivasculitis. Condition in 6 patients who received active treatment targeting improved in the early stage. Three patients (3/7, 42.9%) died due to disease progression during follow-up period.Conclusions: Cryoglobulinemia with cardiac involvement is a rare but serious condition that has relatively high risk of death. When patients with cryoglobulinemia without underlying heart disease experience heart failure, chest pain, or elevation of asymptomatic NT-proBNP and BNP, there is a high possibility of cardiac involvement, even if the electrocardiogram and troponin are negative. Further examinations such as echocardiography, cardiac magnetic resonance imaging, and myocardial biopsy examination could contribute to the diagnosis. Cardiac manifestations could be timely reversed after active targeted treatment. NT-proBNP and echocardiography could be used for the monitoring of disease efficacy.

Comparative analysis of phasic left atrial strain and left ventricular posterolateral strain to discriminate Fabry cardiomyopathy from other forms of left ventricular hypertrophy

Background “Classic” echocardiographic signs of Fabry cardiomyopathy (FC), such as left ventricular hypertrophy (LVH) and posterolateral strain deficiency (PLSD) have a low diagnostic accuracy in clinical practice. Purpose Our aim was to evaluate the diagnostic accuracy of phasic left atrial strain impairment compared to PLSD to discriminate FC from other forms of LVH. Methods 40 patients with LVH due to bioptically and genetically confirmed FC or with LVH due to other causes, defined by exclusion of storage diseases, such as Amyloidosis or FC, by myocardial biopsy, were retrospectively analysed. Standard echocardiographic views (Vivid E9, GE, Vingmed, Horton) were used to analyse left atrial (LA) reservoir, conduit, and contraction strain using 2D speckle tracking echocardiography (2DSTE; EchoPAC software, GE) as well as the PLSD, obtained by the mean of deformation values in basal posterior and lateral segments in a 17-segment model. Receiver operating characteristic (ROC) curve analysis and a logistic regression model were performed to assess the diagnostic accuracy of LA and LV strain impairment. Results FC was confirmed in 20 patients by genetic testing and myocardial biopsy. In the LVH group, 12 patients were classified to have hypertrophic cardiomyopathy, two had hypertensive heart disease, and six expressed the pattern of LV hypertrophy combined with borderline myocarditis. LV septum thickness (15.8mm±3.4 in FC; 17.9mm±4.3 in LVH) and left atrial volume index (LAVI) (36.7ml/m2±11.3 in FC; 45.7ml/m2±16.3 in LVH) as well as LVEF (54.2%± 9.8 in FC; 52.5%±7.7 in LVH,) were not statistically different between groups. LV filling parameters such as E/A (1.2±0.5 in FC; 1.2±0.7 in LVH) and E/e' (11.0±4.9 in FC; 13.2±5.3 in LVH) showed a slightly more advanced impairment in the LVH group. Global and regional LV function was not different between groups (LVGLS −13.8±3.7% in FC and −12.8±3.7% in LVH; PLSD −10.7±5.2% in FC and −8.85±3.9% in LVH; p-value?). LA reservoir strain (LASr) and LA conduit strain (LAScd) were significantly impaired in FC compared to the LVH group (LASr 14,6±2.5% in FC and 26.3±8.5% in LVH, p<0.01; LAScd −5.9±2.6% in FC and −15.8±4.7% in LVH, p<0.01). In ROC analysis, LASr, with an area under the curve (AUC) of 0.81 (95% CI 0.64–0.97) and LAScd with an AUC of 0.85 (95% CI 0.71–0.99), respectively, showed the highest diagnostic accuracy to discriminate FC. PLSD, in contrast, held a low diagnostic accuracy with an AUC of only 0.47 (95% CI 0.27–0.68). Conclusion A substantially higher diagnostic accuracy could be shown for LASr and LAScd impairment in discriminating FD and other forms of LVH compared to PLSD. The echocardiographic assessment of phasic LA strain may help to identify FC in patients with unclear LVH. FUNDunding Acknowledgement Type of funding sources: None. ROC analysis Representative examples

Endovascular therapy for severely calcified plaque at the superficial femoral artery using myocardial biopsy forceps

Background Currently, the success rate of EVT for treating CTO of the SFA is high; however, EVT is still found to be insufficient in treating CTOs with severely calcified lesions. Even if the guidewire crosses the lesion, the calcifications may still cause difficulties during stent expansion. Main text A 78-year-old male had been reported to have intermittent claudication with chronic total occlusion (CTO) of the right superficial femoral artery (SFA). Angiography revealed severely calcified plaque (Angiographic calcium score: Group4a [1]) at the ostium of the SFA. Stenting posed a risk of underexpansion, causing the plaque to shift to the deep femoral artery. we decided to remove the calcified plaque using biopsy forceps. After removing the extended calcified plaque, the guidewire could cross easily, and the self-expandable stent was well dilated without causing the plaque to shift to the DFA. Conclusions Biopsy forceps may be used in some endovascular cases to remove severely calcified lesions. To ensure the safety of the patient, the physician must be adept at performing this technique before attempting it.

A rare case of nivolumab-related myasthenia gravis and myocarditis in a patient with metastatic gastric cancer

Background Although rare, several immune-related adverse effects can be life-threatening. Here, we describe a metastatic gastric cancer patient presenting with nivolumab-related myasthenia gravis and myocarditis, a previously unreported adverse effect of gastric cancer treatment. Case presentation A 66-year-old man with metastatic gastric cancer visited the emergency department because of dizziness after the first dose of nivolumab. Diagnoses of nivolumab-related myasthenia gravis and myocarditis were established. Myocardial biopsy results and anti-acetylcholine receptor antibody positivity confirmed the diagnoses. Despite plasma exchange and intravenous methylprednisolone and immunoglobulin administration, the patient’s general condition gradually worsened, and he died. Conclusions Strict monitoring for cardiac and neuromuscular symptoms after nivolumab administration is necessary to rapidly treat these adverse effects.

Light-Chain Cardiac Amyloidosis: A Case Report and Review of the Literature

Background: Light-chain (AL) cardiac amyloidosis is a rare cardiomyopathy associated with poor prognosis. Due to the advances of imaging technology, cardiac amyloidosis can be now sufficiently diagnosed without myocardial biopsy. Case presentation: This study reports a 69-year-old female who was admitted with chest distress, abdominal distension, anorexia, resistant hypotension, oliguria, and hyponatremia. The patient was confirmed as AL cardiac amyloidosis with the aid of cardiac MR 2 years after symptom onset. The patient received palliative care due to the end stage of the disease. Conclusions: Early diagnosis by cardiac imaging and etiology-oriented treatment are of importance to improve prognosis of AL cardiac amyloidosis.

Effectiveness of myocarditis therapy depending on the diagnosis approach (with or without myocardial biopsy)

Aim. To evaluate the effectiveness of myocarditis therapy depending on the diagnosis approach (with or without myocardial biopsy).Material and methods. The study included 83 patients ≥18 years old with severe and moderate myocarditis (25 women and 58 men; mean age, 45,7±11,7 years), established by myocardial biopsy (group 1, n=36) or by a non-invasive diagnostic algorithm (group 2, n=47), for which immunosuppressive therapy (IST) was carried out. Inclusion criteria were left ventricular (LV) end-diastolic dimension >5,5 cm and ejection fraction (EF) <50%. An endomyocardial (n=31) or intraoperative (n=5) biopsy with a study of the viral genome and level of anticardiac antibodies were performed. Coronary angiography (29%), cardiac multislice computed tomography (75%), cardiac magnetic resonance imaging (41%), and 99mTc-MIBI scintigraphy (35%) were also carried out. The mean follow-up period was 3 years (36 [12; 65] months). The study was approved by the Intercollegiate Ethics Committee.Results. The groups were completely comparable in age, baseline parameters (class III [2,25; 3] and III [2; 3] heart failure (HF); end-diastolic LV dimension, 6,7±0,7 and 6,4±0,7 cm; EF, 29,9±8,7 and 31,4±9,3%), the extent of cardiac therapy (excluding the administration rate of в-blockers — 94,4 and 78,7%, p<0,05) and 1ST (methylprednisolone in 91,7 and 89,4% of patients at a mean dose of 24 [16; 32] and 20 [15; 32] mg/day, azathioprine in 50,0 and 46,8% of patients at a mean dose of 150 mg/day or mycophenolate mofetil 2,0 g/day in 30,6% in group 1, hydroxychloroquine 0,2 g/day in 27,8 and 23,4%). Biopsy in group 1 revealed active/borderline (61/39%) myocarditis, in 8 patients — viral genome in the myocardium, including parvovirus B19 in 7 of them. Both groups showed a comparable significant increase in EF after 6 months up to 37,6±8,1 and 42,6±11,5% (p<0,001) and after 27 [12; 54] months up to 43,4±9,6 and 45,5±12,3% (p<0,001), as well as a significant decrease in HF class to 2 [1; 2] in both groups. An increase in EF by ≥10% was recorded in 70 and 72% of patients, respectively. The mortality rate was 13,9 and 12,8%. Taking into account the only transplantation in group 2, the death+transplantation endpoints reached 13,9 and 14,9% of patients (without significant differences between the groups).Conclusion. In patients with severe and moderate myocarditis diagnosed with and without myocardial biopsy, the effectiveness of combined therapy, including IST, was comparable. If it is impossible to perform a biopsy, complex non-invasive strategy makes it possible to diagnose myocarditis with different probability rate and conduct an effective IST, the refusal of which mostly is not justified.

Trans-Septal Myocardial Biopsy in Hypertrophic Cardiomyopathy Using the Liwen Procedure: An Introduction of a Novel Technique

Objective. The purpose of this study was to evaluate the feasibility and safety of myocardial biopsy using a new approach, the Liwen procedure. Background. Myocardial biopsy is essential when other methods could not differentiate other etiologies from hypertrophic obstructive cardiomyopathy (HOCM). Our previous work using intramyocardial radiofrequency ablation for hypertrophic obstructive cardiomyopathy (Liwen procedure) may provide another approach to obtain the myocardial samples. Method. Seventeen patients with HOCM were enrolled for biopsies through percutaneously accessed intramyocardial septum and evaluated possible complications. Results. We obtained 31 specimens from 17 patients with a success rate of sample acquisition 100.0%. The number of myocardial samples taken per patient was 1.8 ± 0.8, and the average length of all samples was 16.7 ± 5.6 mm which could be used for pathological diagnosis. The complications included pericardial effusion with and without tamponade in one patient (5.9%), and no incidence of nonsustained and sustained ventricular tachycardia, conduction abnormity, perforation, stroke, and pneumothorax. The inhospital and 30-day mortality was 0%. Conclusion. This study has shown that myocardial biopsy of the Liwen procedure is relatively safe and technically feasible with adequate tissue sampling, which may help pathological diagnosis and further research of HOCM of diverse etiologies. This trial is registered with NCT04355260.

Improving Endo-Myocardial Biopsy by Real-Time Spectral Tissue Sensing: A Feasibility Study

Objective: The aim of this research is to integrate spectral tissue sensing technology inside a cardiac bioptome for real-time measurements of tissue characteristics. Methods: Bioptome tip and handle components were designed and manufactured to house and guide optical fibers. The designed components were assembled on a cardiac bioptome together with optical fibers. A technical feasibility test was carried out to study the functionality of the instrument and the effect of the optical technology on the biopsy performance. Biopsy samples were taken from five different tissue types in a porcine heart and the resulting optical spectra were compared. Results: Spectral tissue sensing fibers were successfully integrated inside a conventional cardiac bioptome. The integrated instrument allowed differentiation between ventricular tissue, blood, and cardiac fat tissue based on blood and fat percentage and amount of scattering. Moreover, differences between scarred and non-scarred tissue were clearly visible. Conclusion: A first step has been made in the use of spectral tissue sensing for the detection of different tissue structures for endo-myocardial biopsy. The instrument was able to differentiate between various tissues, as well as between healthy and diseased cardiac tissues. Future research should focus on measurements of naturally diseased cardiac tissue, repeated measurements with statistical value, and improvements to the instrument design. Significance: Having the ability to measure tissue characteristics prior to acquiring a biopsy sample will not only allow easier positioning of the bioptome at the correct location, but can also prevent sampling undesired tissue or scar tissue from previous biopsies.

Imaging Techniques As An Aid In The Early Detection Of Cardiac Amyloidosis

: The idea that performing a proper succession of imaging tests and techniques allows an accurate and early diagnosis of cardiac amyloidosis, avoiding the need to perform myocardial biopsy, is becoming increasingly popular. Furthermore, being imaging techniques non-invasive, it is possible to perform the follow-up of the pathology through repeated image acquisitions. In the present review, the various innovative imaging methodologies are presented, and it is discussed how they have been applied for early diagnosis of cardiac amyloidosis (CA), also to distinguish the two most frequent subtypes in CA: immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR); this allows to perform the therapy in a targeted and rapid manner.