The correlation between anti-phospholipase A2 receptor antibodies and hypercoagulability in patients with idiopathic membranous nephropathy.

BACKGROUND: Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN. METHODS: A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed. RESULTS: Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value. CONCLUSION: Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.

Effectiveness and safety of KunXian capsule for the treatment of IgA nephropathy.

BACKGROUND: Tripterygium Wilfordii Hook F (TwHF) preparation has been widely used in the treatments of IgA nephropathy (IgAN) in China. However, the effectiveness and safety of the new generation of TwHF preparation, KuxXian capsule, on the treatment of IgAN remains unknown. METHODS: Here, we retrospectively describe our experience treating 55 consecutive IgAN patients with KunXian. We defined complete remission as proteinuria < 0.5 g/24 h and partial remission as proteinuria < 1 g/24 h, each also having > 50% reduction in proteinuria from baseline. RESULTS: At first follow-up after KunXian treatment (5.7 weeks, IQR 4.7-7.9), all but two patients (96%) showed a reduction in proteinuria. The overall median proteinuria decreased from 2.23 g/day at baseline to 0.94 g/day (P < 0.001) at the first follow-up. During a median follow-up of 28 weeks after KunXian administration, 25(45.5%) patients achieved complete remission, 34 (61.8%) patients achieved complete/partial remission. Of the 12 patients discontinued KunXian treatment during the follow-up, the median proteinuria was increased from 0.97 g/24 h to 2.74 g/24 h after a median of 10.9 weeks (P = 0.004). Multivariable Cox models showed that female, treatment switching from previous generation of TwHF preparation, lower initial KunXian dosage, and higher proteinuria at baseline were independently associated proteinuria remission. Of the 20 pre-menopausal females, 12 of them developed oligomenorrhea or menstrual irregularity and ten of them developed amenorrhea. CONCLUSION: KunXian is effectiveness and safety for the treatment of IgA nephropathy. Woman of childbearing age to be informed of the risk of ovarian failure after being treated with TwHF preparations.

An equation to estimate 24-hour total urine protein excretion rate in patients who underwent urine protein testing.

BACKGROUND: The urine protein-creatinine ratio (UPCR) in a spot first-morning urine sample is used to estimate 24-h urine proteinuria (24hUP) in patients who underwent urine protein testing. UPCR cannot be directly compared with 24-h proteinuria. Thus, an equation to estimate 24-h total protein excretion rate, using age, gender, and the UPCR may improve its bias and accuracy in patients who underwent urine protein testing. METHODS: We simultaneously measured 24-h urine protein and the same day's first-morning spot urine from patients with kidney disease. Generalized linear and no-linear models, using age, gender, and UPCR, were constructed to estimate for 24-h urine protein and the best model (NJ equation) was selected to estimated 24 hUP (e24hUP). RESULTS: A total of 5435 paired samples (including a training cohort of 3803 patients and a validation cohort of 1632 patients) were simultaneously measured for UPCR and 24-h urine protein. In the training cohort, the unadjusted UPCR obviously underestimated 24-h urine protein when UPCR ≤1.2 g/g (median bias - 0.17 g/24 h) and overestimated 24-h urine protein when UPCR > 1.2 g/g (median bias 0.53 g/24 h). In the validation cohort, the NJ equation performed better than the unadjusted UPCR, with lower root mean square error (0.81 vs. 1.02, P < 0.001), less bias (median difference between measured and estimated urine protein, - 0.008 vs. 0.12), improved precision (interquartile range of the differences, 0.34 vs. 0.50), and greater accuracy (percentage of estimated urine protein within 30% of measured urine protein, 53.4% vs. 32.2%). Bland-Altman plot indicated that the agreement of spot and daily estimates was less pronounced with 24 hUP > 2 g than lower values. CONCLUSIONS: The NJ e24hUP equation is more accurate than unadjusted UPCR to estimate 24 hUP in patients with kidney disease and could be used for laboratory application.

HLA Alleles and Prognosis of PLA2R-Related Membranous Nephropathy.

BACKGROUND AND OBJECTIVES: Associations between HLA alleles and susceptibility to M-type phospholipase A2 receptor (PLA2R)-related membranous nephropathy have been well defined previously in Chinese patients. However, the relationships between HLA alleles and kidney outcome remain unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Five HLA genes (DRB1, DQA1, DQB1, DRB3, and DRB5) were genotyped in a prospective cohort of 392 patients with PLA2R-related membranous nephropathy. The associations between HLA alleles and kidney outcomes were studied. RESULTS: A total of 79 HLA alleles were identified in this study. Four HLA alleles, DRB1*13:01 (n=12; hazard ratio, 3.7; 95% confidence interval, 1.8 to 7.8; P<0.001), DQB1*06:03 (n=12; hazard ratio, 3.7; 95% confidence interval, 1.8 to 7.8; P<0.001), DRB1*04:05 (n=12; hazard ratio, 3.8; 95% confidence interval, 1.5 to 9.5; P=0.004), and DQB1*03:02 (n=21; hazard ratio, 3.1; 95% confidence interval, 1.4 to 6.7; P=0.005), were associated with a ≥40% eGFR decline during follow-up. DRB1*13:01 and DQB1*06:03 were tightly linked with each other. Forty-four of the 392 patients (11%) carried at least one of the four identified risk HLA alleles in this study. Compared with patients who were negative for all risk HLA alleles, those carrying at least one risk HLA allele had a significant risk of a ≥40% eGFR decline during follow-up (hazard ratio, 3.9; 95% confidence interval, 2.3 to 6.7; P<0.001). After adjusting for age, sex, proteinuria, albumin, eGFR, and anti-PLA2R antibody levels, multivariable Cox analysis showed that patients carrying any of the four risk HLA alleles remained associated with a higher risk of a ≥40% decline in eGFR (hazard ratio, 4.1; 95% confidence interval, 2.3 to 7.1; P<0.001). CONCLUSIONS: Carrying any of the HLA alleles, DRB1*13:01/DQB1*06:03, DRB1*04:05, and DQB1*03:02, was independently associated with poor prognosis in Chinese patients with PLA2R-related membranous nephropathy.

Changes in the Spectrum of Kidney Diseases: An Analysis of 40,759 Biopsy-Proven Cases from 2003 to 2014 in China.

OBJECTIVES: To evaluate the changing spectrum of kidney diseases over time in China using renal biopsy-proven cases. METHODS: All patients over the age of 14 years who were diagnosed with a kidney disease by renal biopsy in the Renal Biopsy Registry of the National Clinical Research Center of Kidney Diseases in Jinling Hospital, Nanjing, from 2003 to 2014 were included. RESULTS: In total, 40,759 cases of renal biopsy were analyzed. The mean age of the patients was 36.59 ± 14.12 years. 52.0$ of the patients were male. Primary glomerulonephritis (PGN), secondary glomerulonephritis, tubulointerstitial disease, and hereditary renal diseases accounted for 67.1, 26.4, 2.9, and 2.5$, respectively. IgA nephropathy (IgAN), membranous nephropathy (MN), minimal change disease, and focal segmental glomerulosclerosis were the leading PGN diagnoses. The frequency of MN increased significantly (p < 0.001) by doubling from 2003 to 2014. An analysis by age category indicated that the frequency of MN increased significantly over time (p < 0.001) in all age categories and increased by more than 2 times in the 14-24 age category. Lupus nephritis (LN) and Henoch-Schönlein purpura nephritis (HSPN) decreased significantly (p < 0.001), diabetic nephropathy (DN) increased nearly twice (p < 0.001), monoclonal immunoglobulin deposition disease (MIDD) tripled (p < 0.001), and hypertensive nephropathy (HT) (p < 0.001) and renal amyloidosis (AMY) (p < 0.05) showed an upward trend. An analysis by age category showed that hepatitis B-related nephritis has significantly decreased in the 14-24 age category (p < 0.001). CONCLUSION: PGN continued to be the predominant kidney disease in China with IgAN being the most common PGN. The frequency of MN increased significantly, with a maximum increase in young adults. LN and HSPN decreased significantly, DN and MIDD increased significantly, and HT and AMY also showed an increasing trend. The kidney disease trends presented in this study serve as a reference point for patient care, disease prevention, and public health interventions.

Mycophenolate Mofetil Combined With Prednisone Versus Full-Dose Prednisone in IgA Nephropathy With Active Proliferative Lesions: A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that patients with immunoglobulin A nephropathy (IgAN) with active proliferative lesions show a good response to immunosuppressive treatment. STUDY DESIGN: Multicenter, prospective, randomized, controlled trial. SETTING & PARTICIPANTS: 176 patients with IgAN with active proliferative lesions (cellular and fibrocellular crescents, endocapillary hypercellularity, or necrosis), proteinuria with protein excretion ≥ 1.0g/24h, and estimated glomerular filtration rate > 30mL/min/1.73m2. INTERVENTION: Mycophenolate mofetil (MMF) group: MMF, 1.5g/d, for 6 months and prednisone, 0.4 to 0.6mg/kg/d, for 2 months and then tapered by 20% per month for the next 4 months; prednisone group: prednisone, 0.8 to 1.0mg/kg/d, for 2 months and then tapered by 20% per month for the next 4 months. All patients were followed up for another 6 months. OUTCOMES: The primary end point was complete remission rate at 6 and 12 months. RESULTS: At baseline, median estimated glomerular filtration rates were 90.2 and 94.3mL/min/1.73m2 and mean proteinuria was protein excretion of 2.37 and 2.47g/24h in the MMF and prednisone groups, respectively. At 6 months, complete remission rates were 37% (32 of 86 patients) and 38% (33 of 88 patients); the between-group difference was not statistically significant (P=0.9). At 12 months, complete remission rates were 48% (35 of 73 patients) and 53% (38 of 72 patients) in the MMF and prednisone groups, respectively; the between-group difference was not statistically significant (P=0.6). Incidences of Cushing syndrome and newly diagnosed diabetes mellitus were lower in the MMF group than in the prednisone group. LIMITATIONS: Not all participants were treated with renin-angiotensin system blockers, relatively short follow-up. CONCLUSIONS: MMF plus prednisone versus full-dose prednisone did not differ in reducing proteinuria, but patients treated with the former had fewer adverse events in patients with IgAN with active proliferative lesions.

Evaluating tacrolimus treatment in idiopathic membranous nephropathy in a cohort of 408 patients.

BACKGROUND: The KDIGO Clinical Practice Guidelines for Glomerulonephritis recommended tacrolimus as an alternative regimen for the initial therapy for Idiopathic membranous nephropathy (IMN), however, large observational studies evaluating tacrolimus treatment in IMN remains rare. METHODS: A total of 408 consecutive IMN patients with nephrotic syndrome who were treated with tacrolimus in Jinling Hospital were included. The effectiveness and safety of tacrolimus treatment in IMN were analyzed in this study. RESULTS: The cumulative partial or complete remission after tacrolimus therapy were 50%, 63% and 67% at 6, 12 and 24 months, respectively, and the cumulative complete remission rates were 4%, 13% and 23%, respectively. Multivariate logistic analysis showed that higher tacrolimus exposure during induction treatment, female gender, higher eGFR and no history of previous immunosuppressive therapy were independently associated with higher probability of remission. A relapse occurred in 101 of the 271 (37.3%) patients with partial or complete remission, and 18 of the 95 (18.9%) patients with complete remission. Tapering duration of tacrolimus and complete remission versus partial remission status were independent factors associated with risk of relapse. A decline in eGFR was the most frequent adverse event during tacrolimus treatment. During tacrolimus treatment, a ≥40% decrease in eGFR was observed in 43 (10.5%) patients. CONCLUSIONS: Low dose tacrolimus is effective for IMN, with a total remission rate of 66% whereas with a rather high rate of relapse. However, the safety of tacrolimus treatment needs to be further validated in large randomized clinical trials.

HLA-DRB1*15:01 and HLA-DRB3*02:02 in PLA2R-Related Membranous Nephropathy.

Idiopathic membranous nephropathy (MN) is associated with HLA; however, the HLA allele involved remains unknown. To identify the HLA risk alleles associated with phospholipase A2 receptor (PLA2R)-related MN in the Chinese population, we sequenced the entire MHC region in DNA samples from 99 patients with PLA2R-related MN, 50 patients with PLA2R-unrelated MN, and 100 healthy subjects. Two HLA risk alleles, HLA-DRB1*15:01 and HLA-DRB3*02:02, independently and strongly associated with an increased risk of PLA2R-related MN. After adjusting for HLA-DRB1*15:01 and HLA-DRB3*02:02, no other alleles showed significant association with PLA2R-related MN. A replication study in an independent cohort of 293 participants with PLA2R-related MN and 285 healthy controls validated these findings. In a joint analysis, a multivariate logistic regression model confirmed that HLA-DRB1*15:01 (odds ratio [OR], 24.9; 95% confidence interval [95% CI], 15.3 to 42.6; P=2.3×10-35) and HLA-DRB3*02:02 (OR, 17.7; 95% CI, 11.0 to 30.3; P=8.0×10-29) independently and strongly associated with PLA2R-related MN. As many as 98.7% of patients with PLA2R-related MN, compared with 43.9% of control subjects, carried at least one HLA risk allele. Subjects with either risk allele had higher odds of developing PLA2R-related MN than those without a risk allele (OR, 98.9; 95% CI, 44.4 to 281.7; P=2.5×10-23). These HLA risk alleles also associated with the age at disease onset in patients with PLA2R-related MN. In conclusion, our findings provide clear evidence that the HLA-DRB1*15:01 and HLA-DRB3*02:02 alleles independently and strongly associate with PLA2R-related MN in the Chinese population.

PLA2R antibodies and PLA2R glomerular deposits in psoriasis patients with membranous nephropathy.

BACKGROUND: The association between psoriasis and membranous nephropathy (MN) remains largely unclear. We examined the prevalence of serum PLA2R antibody and characterized the expression of PLA2R and THSD7A in glomeruli in patients with MN and psoriasis. METHODS: A total of 24 patients with MN without evidence of a secondary cause except psoriasis were enrolled. The clinical and pathological features were retrospectively analyzed. Serum anti-PLA2R antibody was measured using IFA Mosaic. Renal tissue samples stored in the laboratory bio-bank were used for PLA2R staining under immunofluorescence microscopy and THSD7A immunohistochemical analysis. RESULTS: Twenty-four patients (21 male and 3 female) with a mean age of 43.6 ± 15.7 years old were enrolled. Serum anti-PLA2R antibody was positive in 7 patients, which was significantly lower than the positivity observed in idiopathic MN (29.2% vs. 81.7%, P < 0.001). Glomerular PLA2R staining was positive in 7 patients with positive serum anti-PLA2R antibody. THSD7A staining was negative in all 24 patients. During the follow-up visits, 13 patients with negative serum PLA2R antibody achieved CR. In contrast, CR was only achieved in 1 patient with positive serum PLA2R antibody, PR was achieved in 2 patients. CONCLUSIONS: The prevalence of serum anti-PLA2R antibody and glomerular expression of PLA2R was significantly lower in patients with psoriasis and MN than in those with idiopathic MN, and THSD7A staining was negative, suggesting that MN is associated with psoriasis in the majority of patients. However, idiopathic MN might also accompany psoriasis in a minority of psoriatic patients with positive serum anti-PLA2R antibody.

Combined Assessment of Phospholipase A2 Receptor Autoantibodies and Glomerular Deposits in Membranous Nephropathy.

Serum phospholipase A2 receptor antibodies (SAbs) and glomerular phospholipase A2 receptor antigen (GAg) deposits have been observed in idiopathic membranous nephropathy (IMN). However, the clinical application of these two biomarkers, particularly GAg deposition, needs to be further evaluated. We measured SAb concentration by ELISA and GAg deposition by immunofluorescence in 572 patients with biopsy-proven IMN. Overall, 68.5% of patients (392 of 572) had detectable SAb (SAb+), and 98.7% of patients who were SAb+ (387 of 392) and 70.6% of patients who were SAb- (127 of 180) had GAg deposition (GAg+). Compared with patients who were SAb-/GAg+, patients who were SAb+/GAg+ exhibited higher levels of proteinuria (P<0.001) and a lower chance of proteinuria remission (P<0.001). In 52 patients who underwent repeat biopsies, patients who did not achieve remission had a higher SAb+ rate on the first biopsy than patients who went into remission (P=0.001). Furthermore, SAb+ levels persisted in patients who did not achieve remission but significantly decreased in patients who achieved remission by the second biopsy. Patients who did not achieve remission also had a higher GAg+ rate on the first biopsy than patients who achieved remission (P<0.01). Sustained GAg+ deposits correlated with disease relapse. In conclusion, combining the measurements of SAb levels and detection of GAg deposition may provide additional information regarding diagnoses, treatment response, and disease relapse in patients with IMN.

Comparison between patients with IgA nephropathy with minimal change disease and patients with minimal change disease.

OBJECTIVE: To compare the clinicopathological characteristics, treatment response, and prognosis between patients with IgAN nephropathy with minimal change disease (MCD-IgAN) and patients with minimal change disease (MCD). METHODS: 77 patients with biopsy-proven MCD-IgAN from the Jinling Hospital IgAN Registry and 77 patients with MCD followed up for ≥ 3 years were retrospectively reviewed. RESULTS: MCD-IgAN and MCD patients had similar clinical presentations, both were predominantly young males, the disease mainly manifested as nephrotic syndrome, and the patients rarely presented with microscopic hematuria. Compared with the MCD group, patients with MCD-IgAN had lower levels of baseline serum albumin (p < 0.01) and eGFR (p < 0.05), a higher level of urine n-acetylglucosaminidase (p < 0.01), higher proportion of mesangial hypercellularity (M1), and more severe acute tubulointerstitial lesions in renal pathology (p < 0.01, p < 0.01, respectively). After 8 weeks of corticosteroid therapy, no significant differences were observed in the rate of complete remission, partial remission, and no remission between MCDIgAN and MCD patients (88.3% vs. 90.9%, 10.4% vs. 5.2%, 1.3% vs. 3.9%, p > 0.05). The median time to achieve remission was 4 weeks (range 1 - 24 weeks) and 4 weeks (range 1 - 28 weeks), respectively. No significant difference existed in the efficacy of corticosteroid between the two groups. During 3.96 years (range 3.0 - 8.5 years) of follow-up, no patients in the two groups entered end-stage renal disease (ESRD), only 2 patients (2.6%) with MCD-IgAN had > 50% reduction of eGFR. CONCLUSIONS: MCD-IgAN may be controlled well achieving a comparable clinical outcome as MCD but more frequently necessitates additional immunosuppressive medication.

Long-term outcome of IgA nephropathy with minimal change disease: a comparison between patients with and without minimal change disease.

BACKGROUND: The clinicopathological characteristics, treatment response and long-term outcome of immunoglobulin (Ig)A nephropathy with minimal change disease (MCD-IgAN) are not well defined. METHODS: Patients with biopsy-proven MCD-IgAN from the Jinling Hospital IgA nephropathy Registry were systematically reviewed and compared with those with IgA nephropathy without minimal change disease (Non-MCD-IgAN). RESULTS: We compared data of 247 MCD-IgAN patients and 1,121 Non-MCD-IgAN patients. Compared to Non-MCD-IgAN, MCD-IgAN patients were younger,with male predominance, had higher levels of proteinuria, total cholesterol and estimated glomerular filtration rate (eGFR), lower incidence of hypertension and microhematuria, lower level of serum creatinine, and had less severe glomerular, tubulointerstitial and vascular lesions in renal pathology. In the Non-MCD-IgAN group, 157 patients (14.0 %) reached the renal endpoint and 103 patients (9.2 %) entered end-stage renal disease (ESRD). The 5-,10-, 15- and 20-year cumulative renal survival rates from ESRD, calculated by Kaplan-Meier method, were 95.0, 83.0, 72.9 and 65.4 %, respectively. In the MCD-IgAN group, no patients entered ESRD and only 4 (1.6 %) reached the renal endpoint. Patients with MCD-IgAN had a significantly better renal outcome than Non-MCD-IgAN (p < 0.01). At multivariate Cox analysis, proteinuria >1.0 g/day, hypertension, eGFR <60 ml/min/1.73 m(2), hypoproteinemia and hyperuricemia were independent risk factors of renal survival for Non-MCD-IgAN patients [hazard ratio (HR) 3.43, p < 0.001; HR 1.65, p < 0.05; HR 2.61, p < 0.001; HR 2.40, p < 0.001; HR 2.27, p < 0.001, respectively), but not for patients with MCD-IgAN. CONCLUSIONS: The long-term outcome of patients with MCD-IgAN is significantly better than that of patients with Non-MCD-IgAN.

Reversal of active glomerular lesions after immunosuppressive therapy in patients with IgA nephropathy: a repeat-biopsy based observation.

BACKGROUND: Reversal of active glomerular lesions after immunosuppressive treatment in patients with IgA nephropathy (IgAN) and their association with prognosis have not been well established. METHODS: Sixty patients with IgAN who received repeat biopsies after immunosuppressive treatment were recruited. Reversal of renal pathological lesions was evaluated between the first and second biopsy. The end-point was defined as a 30% reduction in estimated glomerular filtration rate (eGFR) or end-stage renal disease after the second biopsy. RESULTS: Active glomerular lesions, i.e. endocapillary hypercellularity (E), crescents (C) and necrosis (N) were markedly decreased at the second biopsy after immunosuppressive therapy (36.7 vs. 8.3%, p < 0.001; 85.0 vs. 25.0%, p < 0.001; and 51.7 vs. 3.3%, p < 0.001). Patients with E, C or N at the first biopsy but reversed at the second biopsy showed significantly decreased median levels of proteinuria and hematuria. Such clinical changes were not observed in those with active lesions at both biopsies. After a median follow-up of 32 months, 25.0% of patients reached the end-point. Repeat biopsy confirmed that only tubular atrophy/interstitial fibrosis was associated with the renal outcome. CONCLUSIONS: Active glomerular lesions can be reversed by immunosuppressive treatment in patients with IgAN. The reversal is accompanied by improvement in proteinuria and hematuria. The reversal of these lesions during the disease process may explain the lack of significant correlation of these lesions with clinical outcomes in the present study as well as in previous evaluation studies of the Oxford classification of IgAN.

[Clinical characterization and outcome of patients with noncompaction of ventricular myocardium].

OBJECTIVE: To analyze the clinical features and outcome of patients with noncompaction of ventricular myocardium (NVM). METHODS: Clinical manifestations, electrocardiograms and echocardiographies data were analyzed in 18 patients with NVM. Mean follow-up period was (11 +/- 5) months. RESULTS: The patients aged from 1.5 to 71 years, 66.7% patients were males, familial history was observed in 2 cases, congestive heart failure was present in 14 cases, thromboembolic event occurred in 1 patient, arrhythmia induced syncopes were diagnosed in 2 patients and 1 patient was asymptomatic. Abnormal electrocardiograms were observed in all patients, including premature ventricular beats (7 cases), heart block (4 cases), and atrial fibrillations (4 cases). Echocardiographies showed that noncompaction of ventricular myocardium localized in the left ventricle in 17 patients, and right ventricle in 1 patient. The extension of noncompaction myocardium was predominantly at the apex (72%). N/C was 2.3 - 3.1. EF was less than 50% in 15 patients. Hypokinetic movements were observed in both noncompacted and compacted segments. During the follow-up, 1 patient with congestive heart failure received heart transplantation. ICD was implanted in one patient due to ventricular tachycardia. One patient suffered from sudden cardiac death. CONCLUSIONS: The most common clinical presentations of NVM are congestive heart failure, cardiac arrhythmias, and thromboembolism. Echocardiography is considered as the best tool for the diagnosis of NVM. ICD, heart transplantation and anticoagulation therapy could improve the prognosis of patients with NVM in selected cases.