scholarly journals Comparative efficacy and safety of mycophenolate mofetil and azathioprine in combination with corticosteroids in the treatment of lymphocytic myocarditis

2021 ◽  
Vol 26 (11) ◽  
pp. 4650
Author(s):  
R. S. Rud ◽  
O. V. Blagova ◽  
E. A. Kogan ◽  
V. M. Novosadov ◽  
A. Yu. Zaitsev ◽  
...  

Aim. To study the efficacy and safety of mycophenolate mofetil (MM) in combination with corticosteroids in the treatment of lymphocytic myocarditis in comparison with a standard combination of corticosteroids and azathioprine.Material and methods. The study included 46 patients aged 18 years and older with severe and moderate lymphocytic myocarditis (men, 34; women 12; mean age, 53,5±13,0 years). The diagnosis was verified using endomyocardial biopsy. Symptom duration averaged 9,5 [4; 20.25] months. All patients had class 3 [2,75; 3] heart failure (HF). The main group included 29 patients who received MM 2 g/day, including six patients — instead of azathioprine, which was canceled due to cytopenia (n=3) or insufficient effect (n=3). The comparison group included 17 patients who received azathioprine 150 [100; 150] mg/day. Patients of both groups also received methylprednisolone at a starting dose of 24 [24; 32] and 24 [24; 24] mg/day and standard HF therapy. In 7/2 patients, the parvovirus B19 genome was detected in the myocardium. In all cases, an increase in anticardiac antibody titers was evidence of immune activity. The average follow-up period was 24 [12; 54] months (at least 6 months).Results. The groups were completely comparable in age, initial characteristics and standard drug therapy. In both groups, a comparable significant increase in the ejection fraction (EF) was noted as follows: from 31,2±7,6 to 44,7±8,3% and from 29±9,1 to 46±11,9% (p<0,001). An excellent response to treatment (an increase in EF by 10% or more) was noted in 68,2% and 66,7% of patients, a good response (by 9-5%) — in 27,3% and 14,3%, a poor response (an increase in less than 5% or a decrease in EF) — in 4,5% and 19,0%, respectively. In both groups, we noted the same significant (p<0,01) decrease in pulmonary artery systolic pressure (36,3±12 to 28,1±6,1 mm Hg in the MM group and from 44,1±8,5 to 30,7±12,1 mm Hg in the azathioprine group), left ventricular (LV) end-diastolic dimension (from 6,4±0,6 to 6±0,7 cm and from 6,2±0,5 to 5,8±0,6 cm), LV end-diastolic volume (from 188,7±55,2 to 178,8±57,1 ml and from 167,8±47,5 to 163,3±61,8 ml), LV end-systolic volume (from 130,3±44,1 to 98,4±32 ml and from 118,1±39 to 94,1±46 ml), left atrial volume (from 98,3±30,3 to 86,7±32,6 ml and from 105±27,4 to 91,2±47,3 ml, p<0,05), as well as mitral regurgitation grade. The incidence of deaths was 2 (6,9%) and 2 (8,7%), transplantation — 1 (3,4%) and 1 (4,3%) patients, death+transplantation end point — 3 (10,3%) and 2 (11,8%) without significant differences between the groups. The presence of the parvovirus B19 genome did not affect the results of treatment. The incidence of infectious complications was comparable in both groups (in one case, MM was completely canceled), no new cytopenia cases were noted during the follow-up period.Conclusion. In patients with moderate and severe virus-negative (except for parvovirus B19) lymphocytic myocarditis, the combination of moderate-dose corticosteroids with mycophenolate mofetil 2 g/day is at least no less effective than the standard regimen of immunosuppressive therapy. There was a tendency towards a more pronounced decrease in anticardiac antibody titers in combination with better tolerance (no cases of cytopenia) in MM group. MM in combination with corticosteroids can be recommended as an alternative treatment regimen for lymphocytic myocarditis.

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
O Blagova ◽  
R S Rud' ◽  
V M Novosadov ◽  
A Y U Zaitsev ◽  
E A Kogan

Abstract Purpose To compare of the efficacy and safety of mycophenolate mofetil (MM) and azathioprine in combination with corticosteroids in the treatment of lymphocytic myocarditis. Methods The study included 45 patients with lymphocytic myocarditis, 34 male, the average age 48.1±11.2 years. The diagnosis of myocarditis is verified by endomyocardial biopsy. In ten patients of both groups, the parvovirus B19 DNA was detected in the myocardium. All patients had heart failure 3 [3; 3] NYHA class. High immune activity was indicated by the presence of anti-heart antibodies in all patients. Group 1 included twenty-six patients who received MM 2 g per day. Twenty of them were naive; six patients received MM instead of azathioprine, which was canceled due to cytopenia and/or insufficient effect. Group 2 included nineteen patients who received azathioprine at an average dose of 100 [75; 150] mg per day. Patients of both groups also received methylprednisolone in an average starting dose 24 [24; 32] mg per day and standard therapy for heart failure. Initial group distribution was random. Patients in both groups did not differ significantly in baseline parameters. The mean follow-up period was 23 [8; 57] months (12 and 34 months in the groups). The study is approved by the university ethics committee. Results The level of anti-heart antibodies significantly decreased in both groups. In both groups there was a significant improvement in the structural and functional parameters of the heart: NYHA class decreased from 3 [2.75; 3] to 2 [1; 2] (group 1, p&lt;0.001) and from 3 [3; 3] to 2 [1; 2] (group 2, p&lt;0.001), LV EF increased initially from 30.6±7.8 to 40.1±7.5% (group 1, p&lt;0.001) and from 27.9±8.1 to 37.1±7.6% (group 2, p&lt;0.01), by the end of follow-up to 45.9±9.0% (group 1, p&lt;0.001) and to 42.4±13.7% (group 2, p&lt;0.01). LV EDD significantly decreased from 6.4±0.6 to 6.1±0.8 cm (p&lt;0.01), left atria size from 4.9±0.7 to 4.3±0.6 cm (p&lt;0.05) and pulmonary arteria systolic pressure from 37.8±12.3 to 29.3±7.6 (p&lt;0.05) only in the group 1. No direct side effects of MM were noted. Cytopenia due to treatment of azathioprine developed in 3 patients and required its replacement. There were no significant differences between groups 1 and 2 in overall mortality (7.7 vs 15.8%) and the transplant + death rate (7.7 vs 21.1%). The better survival in the MM group may be due to a shorter follow-up period. Conclusion In patients with lymphocytic myocarditis, a combination of moderate doses of corticosteroids with MM is at least no less effective and safe than steroids with azathioprine. With a shorter follow-up period, the tendency to lower mortality and a more pronounced improvement in structural parameters with better tolerance was noted in the MM group. MM should be considered as an alternative option in the treatment of isolated lymphocytic myocarditis. FUNDunding Acknowledgement Type of funding sources: None.


2017 ◽  
Vol 89 (8) ◽  
pp. 57-67 ◽  
Author(s):  
O V Blagova ◽  
A V Nedostup ◽  
E A Kogan ◽  
V A Sulimov

Aim. To evaluate the efficiency of immunosuppressive therapy (IST) in virus-negative (V–) and virus-positive (V+) patients with lymphocytic myocarditis (LM). Subjects and methods. 60 patients (45 males) (mean age 46.7±11.8 years) with dilated cardiomyopathy (mean left ventricular (LV) end diastolic size (EDS) 6.7±0.7 cm; ejection fraction (EF) 26.2±9.1%) were examined. The diagnosis of active/borderline LM was verified by right ventricular endomyocardial biopsy in 38 patients, by intraoperative LV biopsy in 10, in the study of explanted hearts from 3 patients and at autopsy in 9. The investigators determined the genomes of parvovirus B19, herpes viruses types 1, 2 and 6, Epstein—Barr (EBV), zoster, and cytomegalovirus in the blood and myocardium and, if antibodies were present in the blood, hepatitis B and C viruses, as well as antibodies against antigens in the endothelium, cardiomyocytes and their nuclei, smooth muscles, fibers of the conducting system. IST was used in terms of histological, immune, and viral activities. IST was performed in 22 V+ patients (Group 1) and in 24 V– patients (Group 2); this was not done in 10 V+ patients (Group 3) and V– patients (Group 4). IST comprised methylprednisolone at a mean dose of 24 mg/day (n=40), hydroxychloroquine 200 mg/day (n=20), azathioprine at a mean dose of 150 mg/day (n=21); antiviral therapy included acyclovir, ganciclovir, intravenous immunoglobulin (n=24). The follow-up period was 19 (7.3—40.3) months. Results. The viral genome was detected in the myocardium of 32 patients who made up a V+ group. The degree of histological activity did not differ in relation to the presence of viral genome in the myocardium. The degree of immune activity (anticardiolipin antibody titers) in the V+ patients was as high as that in V– ones. At baseline, the V+ patients had a significantly higher LV EDS and a lower EF than the V– patients. Overall, IST only could lead to a significant increase in EF (from 26.5±0.9 to 36.0±10.8%; p


2020 ◽  
Vol 106 ◽  
pp. 102330 ◽  
Author(s):  
Giacomo De Luca ◽  
Corrado Campochiaro ◽  
Silvia Sartorelli ◽  
Giovanni Peretto ◽  
Simone Sala ◽  
...  

2005 ◽  
Vol 99 (4) ◽  
pp. 1422-1427 ◽  
Author(s):  
Titus Kuehne ◽  
B. Kelly Gleason ◽  
Maythem Saeed ◽  
Daniel Turner ◽  
Jochen Weil ◽  
...  

This study was conducted to determine the effects of chronic combined pulmonary stenosis and pulmonary insufficiency (PSPI) on right (RV) and left ventricular (LV) function in young, growing swine. Six pigs with combined PSPI were studied, and data were compared with previously published data of animals with isolated pulmonary insufficiency and controls. Indexes of systolic function (stroke volume, ejection fraction, and cardiac functional reserve), myocardial contractility (slope of the end-systolic pressure-volume and change in pressure over time-end-diastolic volume relationship), and diastolic compliance were assessed within 2 days of intervention and 3 mo later. Magnetic resonance imaging was used to quantify pulmonary insufficiency and ventricular volumes. The conductance catheter was used to obtain indexes of the cardiac functional reserve, diastolic compliance, and myocardial contractility from pressure-volume relations acquired at rest and under dobutamine infusion. In the PSPI group, the pulmonary regurgitant fraction was 34.3 ± 5.8%, the pressure gradient across the site of pulmonary stenosis was 20.9 ± 20 mmHg, and the average RV peak systolic pressure was 70% systemic at 12 wk follow-up. Biventricular resting cardiac outputs and cardiac functional reserves were significantly limited ( P < 0.05), LV diastolic compliance significantly decreased ( P < 0.05), but RV myocardial contractility significantly enhanced ( P < 0.05) compared with control animals at 3-mo follow-up. In the young, developing heart, chronic combined PSPI impairs biventricular systolic pump function and diastolic compliance but preserves RV myocardial contractility.


2018 ◽  
Vol 64 (9) ◽  
pp. 853-860 ◽  
Author(s):  
Roberta da Silva Teixeira ◽  
Bruna Medeiros Gonçalves de Veras ◽  
Kátia Marie Simões e Senna ◽  
Rosângela Caetano

SUMMARY INTRODUCTION Heart failure due to an acute myocardial infarction is a very frequent event, with a tendency to increase according to improvements in the treatment of acute conditions which have led to larger numbers of infarction survivors. OBJECTIVE The aim of this study is to synthesize the evidence, through a systematic review, on efficacy and safety of the device in patients with this basic condition. METHODS Studies published between January 2002 and October 2016 were analysed, having as reference databases Embase, Medline, Cochrane Library, Lilacs, Web of Science and Scopus. The selection of studies, data extraction and methodological quality assessment of studies were examined by two independent reviewers, with disagreements resolved by consensus. RESULTS Only prospective studies without control group were identified. Six studies were included, with averages of 34 participants and follow-up of 13 months. Clinical, functional, hemodynamic and quality of life outcomes were evaluated. The highest mortality rate was 8.4% with 12-month follow-up for unspecified cardiovascular reasons, and heart failure rehospitalization was 29.4% with 36-month follow-up. Statistically significant improvements were found only in some of the studies which evaluating changes in left ventricular volume indices, the distance measured by the six-minute walk test, New York Heart Association functional classification, and quality of life, in pre and post-procedure analysis. CONCLUSIONS The present review indicates that no available quality evidence can assert efficacy and safety of PARACHUTE® in the treatment of heart failure after apical or anterior wall myocardial infarction.


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
S Cimino ◽  
L I Birtolo ◽  
V Maestrini ◽  
F De Leo ◽  
M Vinciguerra ◽  
...  

Abstract Funding Acknowledgements None Aim Different surgical techniques are available for mitral valve (MV) repair in patients with degenerative severe mitral regurgitation (MR). Leaflet resection (LR) and neochordoplasty (NP), both including ring annuloplasty (RA), are the most frequently performed techniques for posterior mitral leaflet prolapse/flail repair. Despite NP technique is supposed to preserve LV physiology more than LR, it is unclear which technique provides the best haemodynamic pattern. In the present study, the results of the two different surgical techniques in terms of left ventricular (LV) dimension and function are investigated. Methods 23 consecutive patients who underwent MV surgical repair were enrolled. All patients underwent, before surgery and after 8 ± 2 months, 2D and 3D echocardiography with automatic (Heart Model, Philips) assessment of LV volumes and ejection fraction (EF), left atrial (LA) volume, right ventricular (RV) dimension and function, pulmonary artery systolic pressure (PASP), MR, tricuspid regurgitation (TR) and MVPG quantification. MR was corrected using 1) NP with polytetrafluoroethylene sutures and 2) triangular LR, both with RA. Patients were divided in 2 groups according to the surgical technique. Results: techniques were able to successfully correct MR. There were no significant differences in baseline echocardiogram and demographic characteristics between the two groups. There were no significant differences in terms of post-surgical MVPG between the two groups. In all patients a trend in reduction in LV dimension at follow-up was observed, but it was statistically significant only in NP patients (pre-surgical EDV 150 ± 41 VS post-surgical EDV 100 ± 27 ml, p = 0.03). Conclusions Both MV repair techniques showed a successful MV repair and an improvement in LV volumes at follow-up, especially in NP group. Further perspective studies are necessary to demonstrate the hypothesis of more physiological haemodynamic pattern associated with NP techniques. Echo parameters pre VS post MV Repair Parameter pre post p value LVEDV RN (ml) 150 ± 41 100 ± 27 0.03 LVESV RN (ml) 58 ± 20 46 ± 14 NS LVEF RN (%) 58 ± 8 55 ± 7 NS LVEDV RR (ml) 160 ± 58 118 ± 31 NS LVESV RR (ml) 62 ±11 51 ±13 NS LVEF RR (%) 59 ± 8 57 ± 4 NS EDV: end-diastolic volume, ESV: end-systolic volume, EF: ejection fraction, RN = Ring + Neochordae; RR= Ring + Resect.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Kato ◽  
R Padang ◽  
C.G Scott ◽  
M Guerrero ◽  
S.V Pislaru ◽  
...  

Abstract Background Prevalence of calcific mitral stenosis (MS) increases with age. Mitral valve interventions for calcific MS are often delayed until symptoms are severely limiting because the natural history of calcific MS and its relation to cardiac symptoms or comorbidities have not been well assessed. Objectives We assessed the prevalence of symptoms, comorbidities and determinants of all-cause mortality in patients with severe calcific MS. Methods We retrospectively investigated adults with echocardiographic isolated severe MS, defined as mitral valve area (MVA by the continuity equation) ≤1.5 cm2, from July 2003 to December 2017. Among them, calcific MS was identified as obstruction of left ventricular inflow due to degenerative calcification of the mitral annulus using echocardiography and, whenever available, operative findings including histopathological examination. Inactivity was defined as requirement for assistance with activities of daily living. Follow up was obtained by review of medical records. Results Of 491 patients with isolated severe MS, calcific MS was present in 200 (41%; age 78±11 years, 18% men, 32% with atrial fibrillation). Charlson Comorbidity Index (CCI) was 5.1±1.7 and 14 (7%) were inactive. MVA and transmitral gradient (TMG) were 1.26±0.19 cm2 and 8.1±3.8 mmHg, respectively. Symptoms were present at baseline in 120 (60%) including dyspnea in 97, chest discomfort in 12, syncope in 3, lower extremity edema in 3, thrombosis in 3 and fatigue in 2. Of them, mitral valve interventions including surgical or transcatheter mitral valve replacement and mitral valve bypass were performed in 27 (23%): within 1 year after index TTE in 23 (19%) and at 2, 4, 5 and 6 years in 1 each. Of 80 patients without symptoms at index TTE, 20 (25%) developed symptoms at mean 2.9±3.2 years and interventions were performed in 5 (6%). Of 168 who did not receive interventions, 60 (36%) did not develop symptoms during follow up, 58 (35%) were considered to have moderate MS, 46 (27%) were not offered surgery because of high risk due to advanced age, multiple comorbidities or heavy calcification, and 2 (1%) declined interventions. During follow-up of 2.8±3.0 years, Kaplan-Meier survival at 1 and 3 years without intervention were 72% and 52%, respectively (Fig. A). Inactivity, CCI &gt;5, left ventricular ejection fraction (LVEF) &lt;50%, TMG ≥8 mmHg (the mean TMG) and right ventricular systolic pressure (RVSP) ≥50 mmHg were independently associated with mortality (Fig. B). Symptoms were associated with referral for interventions (OR 3.43, 95% CI 1.22–9.65; p=0.019), but not with mortality. Conclusion Patients with isolated severe calcific MS had a high burden of comorbidities and had high mortality without intervention. Symptoms were common (60%), but were not associated with mortality. TMG ≥8 mmHg, RVSP ≥50 mmHg, LVEF&lt;50%, CCI &gt;5 and inactivity were independently associated with mortality. Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Artico ◽  
M Merlo ◽  
G Delcaro ◽  
A Cannata ◽  
P Gentile ◽  
...  

Abstract Background Clinical presentation of myocarditis is extremely heterogeneous from asymptomatic to overt severe heart failure (HF). A complex interaction between pre-existing genetic background and inflammation might be responsible for this heterogeneity. Purpose The aim of the present study was to investigate whether positive genetic background for pathogenic cardiomyopathy-related variants might underlie a higher susceptibility to left ventricular dysfunction in patients with active lymphocytic myocarditis. Methods We prospectively performed genetic tests in 36 patients (46±15 years; 61% males; no relatives included) with biopsy-proven active lymphocytic myocarditis according to Dallas criteria and immunohistochemistry. Only pathogenic (P) or likely pathogenic (LP) variants were considered. Results After genetic test, 31% of patients (n=11) were carriers of P/LP truncating variants in structural Cardiomyopathy related genes: Titin (TTN, n=8, 73%), Desmoplakin (DSP, n=1), Filamin C (FLNC, n=1) and RNA binding protein 20 (RBM20, n=1). Among the 27 patients presenting with HF and LV dysfunction, the positive genetic yield was similar to the total cohort (n=9, 34%; 90% with TTN). Two out of six arrhythmic patients (30%) were carriers in arrhythmogenic genes (i.e. DSP and FLNC), whereas no patients with infarct-like presentation were carriers. During follow-up, 44% of patients (n=16) presented normal Left Ventricular Ejection Fraction (LVEF). Carriers had a lower rate of LVEF normalization compared to non-carriers (18% vs 56%, respectively; p=0.035). Conclusion Positive genetic testing for cardiomyopathy-related-genes might be found in a non-negligible percentage of patients with biopsy-proven myocarditis, especially if presenting with heart failure and LV dysfunction. Compared to non-carriers, carriers of P/LP variants show lower likelihood of LVEF normalization during follow-up. Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
M Previtero ◽  
A C Guta ◽  
R C Ochoa-Jimenez ◽  
S Figliozzi ◽  
C Palermo ◽  
...  

Abstract Background Morbidity and mortality associated with severe tricuspid regurgitation (TR) have prompted interest in new corrective transcatheter procedures. However, to properly select patients for interventional procedures, and to assess their effectiveness, a reliable and reproducible grading system of TR severity is mandatory. However, the cut-off values used by current guidelines to differentiate among mild, moderate and severe TR lack clinical validation. Purpose We aimed to obtain the threshold values of the currently recommended quantitative echocardiographic parameters used to grade TR severity using pts’ outcome as a reference. Methods 296 pts, with at least mild TR and complete 2D, 3D and Doppler echocardiographic study, were enrolled and assessed for potential confounders: age, NYHA class, left ventricular ejection fraction, coexistent valvular heart disease and right ventricular (RV) systolic pressure. Average diameter of the vena contracta (VCavg), effective regurgitant orifice area (EROA), regurgitant volume (RVol) and regurgitant fraction (RF) were obtained to grade TR severity. Median follow-up was 47 (17-80) months. The primary composite endpoint was the occurrence of death of any cause or hospitalization for right heart failure (RHF). Survival curves for the composite endpoint were divided in quartiles at median follow-up. Cut-off values for the echo parameters were derived to grade mild (below the 1st quartile), moderate (between 1st and 3rd quartiles), and severe (above the 3r quartile) TR. Results 33 deaths and 72 hospitalizations for RHF occurred. Event-free rate from death or RHF at the end of follow-up was 14%, 46% and 93% in pts with severe, moderate, and mild TR, respectively. Differences reached statistical significance early (at 1 month), and lasted during the whole follow-up period (Figure). The new threshold values for mild, moderate and severe TR are summarized in Table. Conclusions Partition values of quantitative echo-Doppler parameters used to grade mild, moderate and severe TR according to pts’ clinical outcome are significantly lower than those currently reported in guidelines. Further studies are needed to test if these new threshold values for severe TR will translate in earlier referral of pts to valve repair and improved prognosis. Mild Moderate Severe VCavg &lt;3 mm 3-6 mm &gt;6 mm EROA &lt;0.15 cm&sup2; 0.15-0.30 cm&sup2; &gt;0.30 cm&sup2; R Vol &lt;15 ml 15-30 ml &gt;30 ml RF &lt;25% 25-45% &gt;45% Abstract 38 Figure.


2021 ◽  
Vol 7 ◽  
Author(s):  
Yuji Xie ◽  
Lufang Wang ◽  
Meng Li ◽  
He Li ◽  
Shuangshuang Zhu ◽  
...  

Background: Biventricular longitudinal strain has been recently demonstrated to be predictive of poor outcomes in various cardiovascular settings. Therefore, this study sought to investigate the prognostic implications of biventricular longitudinal strain in patients with coronavirus disease 2019 (COVID-19).Methods: We enrolled 132 consecutive patients with COVID-19. Left ventricular global longitudinal strain from the apical four-chamber views (LV GLS4CH) and right ventricular free wall longitudinal strain (RV FWLS) were obtained using two-dimensional speckle-tracking echocardiography.Results: Compared with patients without cardiac injury, those with cardiac injury had higher levels of coagulopathy and inflammatory biomarkers, higher incidence of complications, more mechanical ventilation therapy, and higher mortality. Patients with cardiac injury displayed decreased LV GLS4CH and RV FWLS, elevated pulmonary artery systolic pressure, and higher proportion of pericardial effusion. Higher biomarkers levels of inflammation and cardiac injury, and the presence of pericardial effusion were correlated with decreases in LV GLS4CH and RV FWLS. During hospitalization, 19 patients died. Compared with survivors, LV GLS4CH and RV FWLS were impaired in non-survivors. At a 3-month follow-up after discharge, significant improvements were observed in LV GLS4CH and RV FWLS. Multivariate Cox analysis revealed that LV GLS4CH [hazard ratio: 1.41; 95% confidence interval [CI]: 1.08 to 1.84; P = 0.011] and RV FWLS (HR: 1.29; 95% CI: 1.09–1.52; P = 0.003) were independent predictors of higher mortality in patients with COVID-19.Conclusions: LV GLS4CH and RV FWLS are independent and strong predictors of higher mortality in COVID-19 patients and can track improvement during the convalescent phase of their illness. Therefore, biventricular longitudinal strain may be crucial for risk stratification and serial follow-up in patients with COVID-19.


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