Invasive and non-invasive quantification of myocardial fibrosis in primary mitral regurgitation: prognostic implications for post-operative remodelling, symptom burden and exercise capacity

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Liu ◽  
K.L.S Khin ◽  
D.A.H Neil ◽  
M Bhabra ◽  
R Patel ◽  
...  
Keyword(s):  
Mitral Regurgitation ◽  
Exercise Capacity ◽  
Myocardial Fibrosis ◽  
Nyha Class ◽  
Symptom Burden ◽  
Class I ◽  
Funding Source ◽  
Non Invasive ◽  
Primary Mitral Regurgitation ◽  
Free Status

Abstract   Chronic primary mitral regurgitation (MR) exposes the left ventricle (LV) to volume overload and is associated with evidence of fibrosis on non-invasive imaging. It is not known whether fibrosis predicts outcome from surgery. This study aimed to 1) quantify myocardial fibrosis on histology and non-invasive imaging, 2) investigate any association between fibrosis and LV size and function, 3) determine the impact of fibrosis on post-operative outcome. Methods In a prospective observational multicentre study, 105 patients with severe MR (N=65/32/8 NYHA Class I/II/III respectively; mean age 63.1±13.4 years; male 73%; VO2max 91.2±22.4%) had multiparametric cardiac magnetic resonance (CMR), symptom assessment (Minnesota Living with Heart Failure Questionnaire (MLHFQ)) and cardiopulmonary exercise testing before and at 9 months following repair. Patients consented for up to 3 intraoperative LV biopsies for histological collagen volume fraction (CVF) quantification. Results 234 LV biopsies were feasible from 86 patients with median CVF of 14.6% [IQR 7.4–20.3]. Fibrosis was present even in NYHA Class I patients (13.6% [6.3–18.8]), and was significantly higher than the 3.3% [2.6–6.1] obtained from 8 autopsy controls without cardiac disease (P<0.001). Pre-operatively, there was no relationship between CVF and LV size, systolic function, ECV, late gadolinium enhancement, although it did correlate with MLHFQ (R=0.23, P=0.034). Conversely, ECV (27.4±3.3%) correlated with systolic (LVEF Rho=−0.22, P=0.029; LVESVi Rho=0.22, P=0.025, GCS Rho=0.31, P=0.002) and diastolic function (E/e' R=0.25, P=0.022), exercise capacity (%VO2max R=−0.22, P=0.030), with borderline correlation to MLHFQ (R=0.19, P=0.058). Post-operatively, although LVEF remained normal (defined as >50%) in all but 6 patients (LVEF pre 69.1±8.0 vs post 63.3±8.3%, P<0.001), there was a reduction in ECV (27.4±3.3 vs 26.6±2.8%, P=0.027) that was proportionate to its pre-operative expansion (Figure1), suggesting that fibrosis was reversible within our patients. Neither histological CVF nor ECV predicted change in LVESVi, LVEF, symptom burden or exercise capacity following repair. GCS was an independent predictor of post-operative LVESVi and LVEF on multiple linear regression models. Whilst improvements in symptom burden and exercise capacity was observed in NYHA II-III patients, this sub-group of patients failed to achieve the same level of fitness and symptom-free status as NYHA I patients (VO2max 92.2±18.8% vs 102.9±21.1%, P=0.017; MLHFQ 12 [5–26] vs 3 [0–10], P<0.001). Conclusions Myocardial fibrosis is present in primary MR, before the onset of symptoms. Due to its patchy nature, ECV but not fibrosis on histology is a better marker of pre-operative myocardial function and symptom status. Despite ECV reduction following successful MR surgery, symptomatic patients fail to regain exercise fitness and symptom-free status – providing further support for the benefits of early surgery. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

scholarly journals Changes of myocardial fibrosis markers with the use of beta-blockers and mineralocorticoid receptor antagonists in patients with heart failure with mid-range ejection fraction of ischemic origin

2021 ◽  
Vol 20 (7) ◽  
pp. 3068
Author(s):  
O. A. Osipova ◽  
E. V. Gosteva ◽  
T. P. Golivets ◽  
O. N. Belousova ◽  
O. A. Zemlyansky ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Myocardial Fibrosis ◽  
Mineralocorticoid Receptor ◽  
Nyha Class ◽  
Class Ii ◽  
Class I ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mineralocorticoid Receptor Antagonist ◽  
Patients With Heart Failure

Aim. To compare the effect of 12-month pharmacotherapy with a betablocker (BB) (bisoprolol and nebivolol) and a combination of BB with a mineralocorticoid receptor antagonist (bisoprolol+eplerenone, nebivolol+eplerenone) on following fibrosis markers: matrix metalloproteinases 1 and 9 (MMP-1, MMP-9) and tissue inhibitor of MMP-1 (TIMP-1) in patients with heart failure with mid-range ejection fraction (HFmrEF) of ischemic origin.Material and methods. The study included 135 patients, including 40 (29,6%) women and 95 (70,4%) men aged 45-60 years (mean age, 53,1±5,7 years). Patients were randomized into subgroups based on pharmacotherapy with BB (bisoprolol or nebivolol) and their combination with eplerenone. The enzyme-linked immunosorbent assay was used to determine the level of MMP-1, MMP-9, TIMP-1 (ng/ml) using the commercial test system “MMP-1 ELISA”, “MMP-9 ELISA”, “Human TIMP-1 ELISA” (“Bender Medsystems “, Austria).Results. In patients with HFmrEF of ischemic origin, there were following downward changes in serum level of myocardial fibrosis markers, depending on the therapy: bisoprolol  — MMP-1 decreased by 35% (p<0,01), MMP-9  — by 56,3% (p<0,001), TIMP-1  — by 17,9% (p<0,01); nebivolol  — MMP-1 decreased by 45% (p<0,001), MMP-9  — by 57,1% (p<0,001), TIMP-1  — by 30,1% (p<0,01); combination of bisoprolol with eplerenone  — MMP-1 decreased by 43% (p<0,001), MMP-9  — by 51,2% (p<0,001), TIMP-1  — by 25,1% (p<0,01); combination of nebivolol with eplerenone  — MMP-1 decreased by 53% (p<0,001), MMP-9 — by 64,3% (p<0,001), TIMP-1 — by 39% (p<0,01). In patients with NYHA class I HFmrEF after 12-month therapy, the decrease in MMP-1 level was 39,9% (p<0,01), MMP-9  — 57,5% (p<0,001). In class II, the decrease in MMP-1 level was 47% (p<0,001), MMP-9 — 49,7% (p<0,001). A significant decrease in TIMP-1 level was revealed in patients with class I by 29% (p<0,01), in patients with class II by 27,1% (p<0,01) compared with the initial data.Conclusion. A significant decrease in the levels of myocardial fibrosis markers (MMP-1, MMP-9, TIMP-1) was demonstrated in patients with HFmrEF of ischemic origin receiving long-term pharmacotherapy. The most pronounced effect was determined in patients with NYHA class I HF.

scholarly journals P1725 An easily dismissed suspect

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
H Santos ◽  
I Almeida ◽  
H Miranda ◽  
M Santos ◽  
L Almeida ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitral Regurgitation ◽  
Emergency Room ◽  
Constrictive Pericarditis ◽  
Nyha Class ◽  
Left Ventricular ◽  
Class I ◽  
Left Ventricular Ejection ◽  
Mineralocorticoid Receptor Antagonist ◽  
Pericardial Calcification

Abstract Funding Acknowledgements None Introduction Constrictive pericarditis (CP) is a rare etiology of heart failure. Is a chronic inflammatory process, characterized by scarring, fibrosis and pericardial calcification. Several etiologies can be associated with CP, namely infectious, idiopathy and post-surgical. In some cases, CP can extend to the myocardium and/or lead to cardiac dysfunction. Case Report 58 years old woman, active smoking, referred to the emergency room for tachycardia on a routine electrocardiogram. History of 5 months of fatigue and dyspnea to ordinary activities, with progressive aggravation in the last month, associated with weight loss and episodic palpitations. Upon the physical examination presented jugular vein engorgement and peripheral edema. Admission electrocardiogram with atrial flutter at 150 of ventricular frequencies, without other findings. Thoracic radiography without variation (tenues pericardium enhancement), abdominal echography with moderate ascites. Blood work showed elevated liver enzymes, BNP of 230pg/ml, exclusion of infectious tuberculosis and autoimmune panel with isolated positive rheumatoid factor. Transthoracic echocardiography (TTE) at the emergency room show a non-dilated and global left ventricle hypokinesia, with reduced left ventricular ejection fraction (LVEF) and dilatation of the mitral valve ring in the genesis of moderate mitral regurgitation. Anticongestive and antiarrhythmic therapy started with rhythm conversion and clinical improve. Thoracic computed tomography scan reveals an extensive pericardial calcification. 2 months later TTE reveal a preserved LVEF, pericardial calcification, moderate mitral regurgitation, grade III diastolic dysfunction, respiration-related ventricular septal shift, increased of the mitral E-wave velocity with an E/A of 2.76, the peak mitral E-wave decreases 36% with the inspiration, dilated inferior vena cava without respiratory variation. Cardiac magnetic resonance imaging exposes a septal bounce and pericardial calcification, suggestive signs of constrictive pericarditis. The patient waits for cardiac catheterization for confirmation, being with anticoagulation, ACE inhibitors, beta-blockers and mineralocorticoid receptor antagonist medication, remaining in NYHA class I. Discussion Clinical suspicion of CP is key for its identification, since there is not a specific clinical manifestation and generally patients presented heart failure symptoms. Echocardiography is best tool for a clinical physician evaluate heart failure etiologies, and can be used with higher sensitivity and specificity associated to the correct criteria to the diagnosis of CP. Pericardiectomy is the standard treatment, however the moment of its performance is not well established, since patients can remain in NYHA class I several years and the surgical procedure have higher mortality rates.

Abstract 13513: MitraClip ® for Functional Mitral Regurgitation: Outcomes in Over 600 Patients

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Gorav Ailawadi ◽  
D. Scott Lim ◽  
Irving L Kron ◽  
Alfredo Trento ◽  
Saibal Kar ◽  
...  
Keyword(s):  
Coronary Artery ◽  
High Risk ◽  
Mitral Regurgitation ◽  
Nyha Class ◽  
Class I ◽  
Symptom Improvement ◽  
Surgical Risk ◽  
High Risk Patients ◽  
High Surgical Risk ◽  
Risk Patients

Background: The treatment options for degenerative or primary mitral regurgitation (DMR) include mitral surgery and transcatheter edge-to-edge repair (MitraClip). However, the optimal therapy for patients with functional or secondary MR (FMR) remains unclear. The purpose of this study was to evaluate the 1 year outcomes of all patients with FMR undergoing MitraClip in the United States as part of the EVEREST (Endovascular Valve Edge-to-Edge Repair STudy) II study. Methods: Patients treated in the EVEREST II trial (randomized trial and continued access registries) with severe FMR were evaluated. Outcomes at 30 days and 1 year were analyzed and adjudicated by an independent core laboratory. Patients were further stratified by surgical risk (High risk= STS mortality score ≥12% or pre-specified risk factors). Results: A total of 619 patients (mean age=73.4 years) with FMR were treated with MitraClip. Comorbidities were common including coronary artery disease (81.1%), NYHA functional class III/IV (80.3%), and previous coronary artery bypass grafting (55.7%). Device implantation was achieved in 96.4% with a mean hospital stay of 3.3 days and an 87.2% discharge to home. At 30 days, mortality was 3.6% with a major adverse event rate of 9.2%. At 1 year, the survival was 78.3%, while the majority of survivors had MR≤2+ (84.5%) and significantly improved symptoms (83.2% NYHA Class I/II). The left ventricular end diastolic volume (LVEDV) improved from 162.5ml to 152.6ml (P<.001). When comparing high surgical risk patients (n=485; mean STS score=10.6±6.9%) to non-high risk patients (n=134), the 30 day mortality was similar (4.1% vs. 1.5%, P=.19), but the 1 year mortality was worse (22.7% vs. 13.4%, P=.02). Nevertheless, at 1 year, there were similar rates of MR reduction (MR≤2+: 83.9% vs. 87.3%) and improvement in LVEDV (-9.0ml vs -12.6ml). The non-high risk cases had greater symptom improvement (NYHA Class I/II: 91.2% vs. 80.2%, P=.001). Conclusions: MitraClip in patients with severe FMR is associated with excellent safety, positive ventricular remodeling, symptom improvement, and stable MR reduction at 1 year independent of surgical risk. Compared to high surgical risk patients, non-high risk patients may derive the greatest survival and symptom benefit.

scholarly journals Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Boyang Liu ◽  
Desley A. H. Neil ◽  
Monisha Premchand ◽  
Moninder Bhabra ◽  
Ramesh Patel ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Mitral Regurgitation ◽  
Exercise Capacity ◽  
Myocardial Fibrosis ◽  
Myocardial Dysfunction ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Lv Function ◽  
Tissue Characterisation

Abstract Background Myocardial fibrosis occurs in end-stage heart failure secondary to mitral regurgitation (MR), but it is not known whether this is present before onset of symptoms or myocardial dysfunction. This study aimed to characterise myocardial fibrosis in chronic severe primary MR on histology, compare this to tissue characterisation on cardiovascular magnetic resonance (CMR) imaging, and investigate associations with symptoms, left ventricular (LV) function, and exercise capacity. Methods Patients with class I or IIa indications for surgery underwent CMR and cardiopulmonary exercise testing. LV biopsies were taken at surgery and the extent of fibrosis was quantified on histology using collagen volume fraction (CVFmean) compared to autopsy controls without cardiac pathology. Results 120 consecutive patients (64 ± 13 years; 71% male) were recruited; 105 patients underwent MV repair while 15 chose conservative management. LV biopsies were obtained in 86 patients (234 biopsy samples in total). MR patients had more fibrosis compared to 8 autopsy controls (median: 14.6% [interquartile range 7.4–20.3] vs. 3.3% [2.6–6.1], P < 0.001); this difference persisted in the asymptomatic patients (CVFmean 13.6% [6.3–18.8], P < 0.001), but severity of fibrosis was not significantly higher in NYHA II-III symptomatic MR (CVFmean 15.7% [9.9–23.1] (P = 0.083). Fibrosis was patchy across biopsy sites (intraclass correlation 0.23, 95% CI 0.08–0.39, P = 0.001). No significant relationships were identified between CVFmean and CMR tissue characterisation [native T1, extracellular volume (ECV) or late gadolinium enhancement] or measures of LV function [LV ejection fraction (LVEF), global longitudinal strain (GLS)]. Although the range of ECV was small (27.3 ± 3.2%), ECV correlated with multiple measures of LV function (LVEF: Rho = − 0.22, P = 0.029, GLS: Rho = 0.29, P = 0.003), as well as NTproBNP (Rho = 0.54, P < 0.001) and exercise capacity (%PredVO2max: R = − 0.22, P = 0.030). Conclusions Patients with chronic primary MR have increased fibrosis before the onset of symptoms. Due to the patchy nature of fibrosis, CMR derived ECV may be a better marker of global myocardial status. Clinical trial registration Mitral FINDER study; Clinical Trials NCT02355418, Registered 4 February 2015, https://clinicaltrials.gov/ct2/show/NCT02355418

P6468Balloon pulmonary angioplasty for patients with symptomatic chronic thromboembolic disease without pulmonary hypertension

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Taniguchi ◽  
Y Matsuoka ◽  
H Onishi ◽  
K Yanaka ◽  
K Nakayama ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Exercise Capacity ◽  
Nyha Class ◽  
Pulmonary Arteries ◽  
Functional Class ◽  
Thromboembolic Disease ◽  
Class I ◽  
P Value ◽  
Peak Vo2 ◽  
Chronic Thromboembolic Disease

Abstract Background Chronic thromboembolic disease (CTED) is characterised by thromboembolic stenosis and obstruction of pulmonary arteries without pulmonary hypertension. The treatment approach for symptomatic patients with CTED is still controversial. It has been reported the efficacy of surgical endarterectomy for patients with CTED, however that of balloon pulmonary angioplasty (BPA) for non-operable CTED has not been well established. Method We started aggressive BPA protocol for non-operable CTED patients who suffered from symptom with NYHA class II, III, and IV or limitation of exercise in spite of mean pulmonary artery pressure (mPAP) <25 mmHg since February 2014. We evaluated subjective symptoms, hemodynamic parameters by right heart catheter, and exercise capacity by cardiopulmonary exercise test at baseline and after the last BPA session. Results Twenty-three patients with CTED (68.7±10.5 years-old, 7 male) had undergone BPA. In these, 7 patients had received pulmonary vasodilators previously. After 2.9±1.3 sessions of BPA, Further improvement was observed in hemodynamics such as mPAP (21.6±2.3 to 17.1±2.6 mmHg, p<0.01), pulmonary vascular resistance (278±80 to 198±63 dyne/s/cm–5, p<0.01), which were accompanied with improved peak VO2 (14.6±4.4 to 17.4±4.2 ml/min/kg, p<0.01), VE/VCO2 slope (39.6±14.6 to 30.2±6.0, p=0.01), and functional class (I/II/III/IV; 0/10/12/1 to 9/12/2/0, p<0.01) (Table). All patients were tolerable, and no severe complication regarding to BPA. Table 1 Variables Baseline After BPA (3 month) P value NYHA class (I / II / III / IV) 0 / 10 / 12 / 1 9 / 12 / 2 / 0 <0.01 Mean PAP (mmHg) 21.6±2.3 17.1±2.6 <0.01 PVR (dyne/sec/cm–5) 278±80 198±63 <0.01 6 MWD (m) 354±93 382±96 0.09 Peak VO2 (ml/min/kg) 14.6±4.4 17.4±4.2 <0.01 Conclusion BPA may have the potential to achieve further improvement of exercise capacity and symptoms in CTED patients with acceptable risk, therefore BPA should be considered as a treatment option for symptomatic patients with non-operable CTED.

Recovering from acute heart events

2020 ◽  
pp. 35-40
Author(s):  
Ugo Corrà ◽  
Jean-Paul Schmid
Keyword(s):  
Exercise Capacity ◽  
Heart Surgery ◽  
Nyha Class ◽  
Clinical Status ◽  
Psychosocial Health ◽  
Class I ◽  
Level Of Evidence ◽  
Functional Exercise ◽  
Related Quality ◽  
Health Related

Despite extraordinary advances in pharmacological and interventional therapies, cardiac rehabilitation (CR) and secondary prevention programmes have maintained a class I indication with level of evidence A in patients after acute coronary syndrome (ACS) and a class I recommendation with level of evidence B in patients after surgical revascularization and with chronic ischaemic heart disease (IHD). In post-acute or chronic heart failure (New York Heart Association (NYHA) class II–III, both with reduced or preserved ejection fraction (EF)), CR has a class I recommendation with level of evidence A. In patients with recent valvular heart surgery, there is an important indication for CR intervention early after surgery. Once admitted to CR, patients should have their clinical status assessed or reviewed before starting any activities, particularly exercise training. Assessment should cover medical history, personal goals and preferences, physical parameters, disease-specific status, disease management, psychosocial health, risk factors, functional exercise capacity, health-related quality of life (HRQoL), and the impact of physical deconditioning of comorbidities. Previous exercise levels, aids used, goals, and residual exercise capacity/function should also be considered. If patients are not clinically stable, CR interventions should be deferred. However, if patients are stable, intervention should be started as soon as possible after an acute cardiac event after appropriate functional assessment.

Invasive exercise hemodynamics in patients with severe primary mitral regurgitation and preserved ejection fraction predicts future valve surgery

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Hein ◽  
J.N Neu ◽  
S.D Dorfs ◽  
S.D Doerken ◽  
W.Z Zeh ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Ejection Fraction ◽  
Mitral Valve Surgery ◽  
Left Ventricular ◽  
Valve Surgery ◽  
Non Invasive ◽  
Asymptomatic Patients ◽  
Exercise Hemodynamics ◽  
Primary Mitral Regurgitation

Abstract Background The role of invasive exercise hemodynamics in the management of asymptomatic patients with severe primary mitral regurgitation (MR) is unclear. Methods and results We compared the predictive power of parameters of invasive exercise testing for future valve surgery to guideline-defined non-invasive criteria. Maximal pulmonary capillary wedge pressure (PCWP), PCWP normalized to workload and weight (PCWL), and invasive maximal systolic pulmonary artery pressure (SPAP) were assessed in 113 asymptomatic patients with severe primary MR between 1996 and 2012. Mean age was 52±11 years, 16% were female, ejection fraction was ≥55% in all patients. During a median follow up of 4.5 years (IQR2.0; 8.3) 54 patients (48%) underwent valve surgery. In univariate analysis PCWP (P&lt;0.001), PCWL (P&lt;0.001), and maximal SPAP (P=0.009) were significantly associated with future mitral valve surgery. In multivariate analysis maximum PCWP and PCWL predicted future mitral valve surgery (HR 2.1 (1.44–3.10), P=0.005 and HR 1.31 (1.14–1.52), P&lt;0.001, respectively) whereas SPAP did not. Adding maximum PCWP &gt;25mmHg to a Cox regression model based on non-invasive guideline criteria resulted in a significant increase in the area under the curve (0.61 to 0.68, P=0.02). Conclusion In asymptomatic patients with severe primary mitral regurgitation and preserved left ventricular function invasive exercise hemodynamics improves information derived from current non-invasive guideline criteria. Figure 1 Funding Acknowledgement Type of funding source: None

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