scholarly journals Titin-Related Dilated Cardiomyopathy: The Clinical Trajectory and the Role of Circulating Biomarkers in the Clinical Assessment

Diagnostics ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 13
Author(s):  
Przemysław Chmielewski ◽  
Grażyna Truszkowska ◽  
Ilona Kowalik ◽  
Małgorzata Rydzanicz ◽  
Ewa Michalak ◽  
...  

Titin truncating variants (TTNtv) are known as the leading cause of inherited dilated cardiomyopathy (DCM). Nevertheless, it is unclear whether circulating cardiac biomarkers are helpful in detection and risk assessment. We sought to assess 1) early indicators of cardiotitinopathy including the serum biomarkers high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in clinically stable patients, and 2) predictors of outcome among TTNtv carriers. Our single-center cohort consisted of 108 TTNtv carriers (including 70 DCM patients) from 43 families. Clinical, laboratory and follow-up data were analyzed. The earliest abnormality was left ventricular dysfunction, present in 8, 26 and 47% of patients in the second, third and fourth decade of life, respectively. It was followed by symptoms of heart failure, linked to NT-proBNP elevation and severe left ventricular systolic dysfunction, and later by arrhythmias. Hs-cTnT serum levels were increased in the late stage of the disease only. During the median follow-up of 5.2 years, both malignant ventricular arrhythmia (MVA) and end-stage heart failure (esHF) occurred in 12% of TTNtv carriers. In multivariable analysis, NT-proBNP level ≥650 pg/mL was the best predictor of both composite endpoints (MVA and esHF) and of MVA alone. In conclusion, echocardiographic abnormalities are the first detectable anomalies in the course of cardiotitinopathies. The assessment of circulating cardiac biomarkers is not useful in the detection of the disease onset but may be helpful in risk assessment.

2021 ◽  
Author(s):  
Przemysław Chmielewski ◽  
Grażyna Truszkowska ◽  
Ilona Kowalik ◽  
Małgorzata Rydzanicz ◽  
Ewa Michalak ◽  
...  

Abstract Titin truncating variants (TTNtv) are known as the leading cause of inherited dilated cardiomyopathy (DCM). Nevertheless, the clinical course is not fully understood and it is unclear whether circulating cardiac biomarkers are helpful in the detection and risk assessment. We sought to assess: 1) early signs of cardiotitinopathy including serum biomarkers: high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in clinically stable patients, and 2) indicators of outcome among TTNtv carriers. Our single-centre cohort included 108 carriers (including 70 DCM patients) from 43 families. Clinical, laboratory and follow-up data were analyzed. The earliest abnormality was left ventricular dysfunction, present in 8, 26 and 47% of patients in the 2nd, 3rd and 4th decade of life, respectively. It was followed by symptoms of heart failure and elevation of NT-proBNP, linked to severe (persistent or transient) left ventricular systolic dysfunction, and later by arrhythmias, preceding both malignant ventricular arrhythmia (MVA) and end-stage heart failure (esHF). Hs-cTnT serum levels were increased in the late stage of the disease only. During the median follow-up of 5.2 years both MVA and esHF occurred in 12% of TTNtv carriers. In multivariable analysis, NT-proBNP level ≥650 pg/ml was the best predictor of both composite endpoint (MVA and esHF), and of MVA alone. We conclude that assessment of circulating cardiac biomarkers is not useful in the detection of cardiotitinopathies but may be helpful in the risk assessment.


2020 ◽  
Vol 21 (3) ◽  
pp. 807 ◽  
Author(s):  
Iwona Świątkiewicz ◽  
Przemysław Magielski ◽  
Jacek Kubica ◽  
Adena Zadourian ◽  
Anthony N. DeMaria ◽  
...  

Acute ST-segment elevation myocardial infarction (STEMI) activates inflammation that can contribute to left ventricular systolic dysfunction (LVSD) and heart failure (HF). The objective of this study was to examine whether high-sensitivity C-reactive protein (CRP) concentration is predictive of long-term post-infarct LVSD and HF. In 204 patients with a first STEMI, CRP was measured at hospital admission, 24 h (CRP24), discharge (CRPDC), and 1 month after discharge (CRP1M). LVSD at 6 months after discharge (LVSD6M) and hospitalization for HF in long-term multi-year follow-up were prospectively evaluated. LVSD6M occurred in 17.6% of patients. HF hospitalization within a median follow-up of 5.6 years occurred in 45.7% of patients with LVSD6M vs. 4.9% without LVSD6M (p < 0.0001). Compared to patients without LVSD6M, the patients with LVSD6M had higher CRP24 and CRPDC and persistent CRP1M ≥ 2 mg/L. CRP levels were also higher in patients in whom LVSD persisted at 6 months (51% of all patients who had LVSD at discharge upon index STEMI) vs. patients in whom LVSD resolved. In multivariable analysis, CRP24 ≥ 19.67 mg/L improved the prediction of LVSD6M with an increased odds ratio of 1.47 (p < 0.01). Patients with LVSD6M who developed HF had the highest CRP during index STEMI. Elevated CRP concentration during STEMI can serve as a synergistic marker for risk of long-term LVSD and HF.


Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 654
Author(s):  
Weinmann ◽  
Werner ◽  
Koenig ◽  
Rottbauer ◽  
Walcher ◽  
...  

Immunoadsorption and subsequent administration of intravenous immunoglobulin (IVIG) have shown beneficial effects on cardiac function and symptoms in patients with dilated cardiomyopathy. Biomarkers play an emerging role in disease monitoring and outcome prediction of heart failure (HF) patients. We aimed to analyze cardiac biomarkers as predictor for improvement of left ventricular (LV) function after immunoadsorption treatment in dilated cardiomyopathy (DCM). Thirty-one patients with dilated cardiomyopathy on optimized HF pharmacotherapy received a single cycle of immunoadsorption for five days followed by IVIG administration. Left ventricular ejection fraction (LVEF) and heart failure biomarkers (hs troponin T, hs troponin I, NT-proBNP and sST2) were evaluated before treatment, after the last cycle of immunoadsorption and during a median follow-up of 30.5 months. We correlated HF biomarkers before immunoadsorption and acute changes of HF biomarkers by immunoadsorption with LV improvement during the long-term follow-up. LV function improved significantly after immunoadsorption from 28.0 to 42.0% during the long-term follow-up (p < 0.0001). Evaluation of biomarker levels showed a significant decrease for hs troponin I (from 9.2 to 5.5 ng/L, p < 0.05) and NT-proBNP (from 789.6 to 281.2 pg/mL, p < 0.005). Correlation of biomarker levels before immunoadsorption and LVEF at the long-term follow-up show good results for hs troponin T (r = −0.40, r2 = 0.16, p < 0.05), hs troponin I (r = −0.41, r2 = 0.17, p < 0.05) and sST2 (r = −0.46, r2 = 0.19, p < 0.05). Correlation of biomarker levels before immunoadsorption and the individual increase in LV function was significant for hs troponin T (r = −0.52, r2 = 0.27, p < 0.005) and hs troponin I (r = −0.53, r2 = 0.29, p < 0.005). To imply a tool for monitoring outcome immediately after immunoadsorption treatment, we investigated the correlation of acute changes of biomarker levels by immunoadsorption treatment and individual increase in LV function. A drop in hs troponin T (r = −0.41, r2 = 0.17, p < 0.05) and hs troponin I (r = −0.53, r2 = 0.28, p < 0.005) levels demonstrate a good correlation to improvement in LVEF during the long-term follow-up. Conclusion: Hs troponin T and I levels correlate with LV function improvement during long-term follow-up. Acute decrease of troponins by immunoadsorption treatment is paralleled by individual improvement of LVEF at the long-term follow-up. Thus, troponins could serve as a monitoring tool for the improvement of LV function after immunoadsorption treatment in dilated cardiomyopathy.


2020 ◽  
Vol 9 (5) ◽  
pp. 1443 ◽  
Author(s):  
Przemyslaw Chmielewski ◽  
Ewa Michalak ◽  
Ilona Kowalik ◽  
Maria Franaszczyk ◽  
Malgorzata Sobieszczanska-Malek ◽  
...  

Mutations in the lamin A/C gene are variably phenotypically expressed; however, it is unclear whether circulating cardiac biomarkers are helpful in the detection and risk assessment of cardiolaminopathies. We sought to assess (1) clinical characteristics including serum biomarkers: high sensitivity troponin T (hsTnT) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in clinically stable cardiolaminopathy patients, and (2) outcome among pathogenic/likely pathogenic lamin A/C gene (LMNA) mutation carriers. Our single-centre cohort included 53 patients from 21 families. Clinical, laboratory, follow-up data were analysed. Median follow-up was 1522 days. The earliest abnormality, emerging in the second and third decades of life, was elevated hsTnT (in 12% and in 27% of patients, respectively), followed by the presence of atrioventricular block, heart failure, and malignant ventricular arrhythmia (MVA). In patients with missense vs. other mutations, we found no difference in MVA occurrence and, surprisingly, worse transplant-free survival. Increased levels of both hsTnT and NT-proBNP were strongly associated with MVA occurrence (HR > 13, p ≤ 0.02 in both) in univariable analysis. In multivariable analysis, NT-proBNP level > 150 pg/mL was the only independent indicator of MVA. We conclude that assessment of circulating cardiac biomarkers may help in the detection and risk assessment of cardiolaminopathies.


2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
A Vera Sainz ◽  
A Cecconi ◽  
P Martinez-Vives ◽  
MJ Olivera ◽  
S Hernandez ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background In patients admitted for heart failure (HF) with reduced left ventricular ejection fraction (LVEF) and a concomitant high-rate supraventricular tachyarrhythmia (SVT) it is challenging to predict LVEF recovery after heart rate control and distinguish tachycardia-induced cardiomyopathy (TIC) from dilated cardiomyopathy (DC). The role of cardiac magnetic resonance (CMR) and the electrocardiogram (ECG) in this setting remains unsettled. Methods Forty-three consecutive patients admitted for HF due to high-rate SVT and LVEF &lt;50% undergoing CMR in the acute phase were retrospectively included. Those who had LVEF &gt;50% at follow up were classified as TIC and those with LVEF &lt;50% were classified as DC. Clinical, laboratory, CMR and ECG findings were analyzed to predict LVEF recovery. Results Twenty-five (58%) patients were classified as TIC. Patients with DC had wider QRS (121.2 ± 26 vs 97.7 ± 17.35 ms; p = 0.003). On CRM the TIC group presented with higher LVEF (33.4 ± 11 vs 26.9 ± 6.4% p = 0.019) whereas late gadolinium enhancement (LGE) was more frequent in DC group (61 vs 16% p = 0.004). On multivariate analysis, QRS duration ≥100 ms (p = 0.027), LVEF &lt; 40% on CMR (p = 0.047) and presence of LGE (p = 0.03) were identified as independent predictors of lack of LVEF recovery. Furthermore, during clinical follow-up (median 60 months) DC patients were admitted more frequently for HF (44% vs 0%; p &lt; 0.001) than TIC patients (Figure 1). Conclusion In patients with reduced LVEF admitted for HF due to high-rate SVT, QRS duration ≥100 ms, LVEF &lt;40% on CMR and presence of LGE are independently associated with lack of LVEF recovery and worse clinical outcome.


2018 ◽  
Vol 159 (25) ◽  
pp. 1009-1012
Author(s):  
János Tomcsányi ◽  
Miklós Somlói ◽  
Béla Bózsik ◽  
Tamás Frész ◽  
Erzsébet Nagy

Abstract: Introduction: The determination of natriuretic peptide levels in patients hospitalized for suspected acute heart failure is important for the confirmation of the diagnosis and for the prognosis. Changes in natriuretic peptide levels in response to therapy have a strong prognostic value. Aim: To decide whether repeated natriuretic peptide measurements for acute heart failure show changes that could influence the diagnosis and/or the prognosis. Method: Prospective data collection was carried out of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels on admission and within 12 hours in patients hospitalized for acute heart failure. Only the data of those patients were analyzed whose symptoms started within 24 hours prior to admission and were due to acute heart failure. Results: The 23 patients whose data we analyzed had an average age of 77.9 ± 8.3 years. Most of them had left ventricular systolic dysfunction with an average ejection fraction of 34.1 ± 3.9%. The time between the start of symptoms and the first measurement was 6.7 ± 2.2 hours, while the time until the repeated determination was 6.5 ± 2.2 hours after the first measurement. The median value of the NT-proBNP levels in the 6 hours control showed an increase from 5064 pg/mL to 8847 pg/mL (p<0.0005), which amounts to a 75 percent increase – mean hs-troponin T showed an increase from 46 ± 25 ng/L to 78 ± 51 ng/L (p<0.002). Conclusions: A significant increase in NT-proBNP levels is to be expected in early repeated measurement after hospital admission. This fact could have diagnostic and prognostic consequences if validated in a larger patient population. Orv Hetil. 2018; 159(25): 1009–1012.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Klimczak-Tomaniak ◽  
V Van Den Berg ◽  
M Strachinaru ◽  
K M Akkerhuis ◽  
S Baart ◽  
...  

Abstract Introduction Linking temporal biomarker evolutions to changes within myocardial structure and function could provide additional insights into the mechanisms that underlie associations between blood biomarkers and clinical outcome, which have been reported in previous studies. Purpose We aimed to investigate whether serum biomarkers reflect the functional state of the heart in a longitudinal setting. We examined the relationship between serial simultaneous measurements of echocardiographic parameters and serum biomarkers C-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin t (hs-TnT) in chronic heart failure (CHF) patients. Materials and methods In total, 117 CHF patients enrolled in a prospective observational study underwent serial measurement of hs-TnT, NT-proBNP and CRP, accompanied by echocardiographic evaluation at six-month intervals until the end of 30-month follow-up or until an adverse clinical event (HF hospitalization, left ventricular assist device implantation, cardiac transplantation, cardiac death) occurred. Linear mixed effects (LME) models were used for data-analysis. Results Mean age was 58±11 years, 80% were male, 76% in NYHA class I or II and all had reduced left ventricular ejection fraction (LVEF). Median follow-up was 2.2 years [IQR: 1.5–2.6]. We performed up to 6 follow-up evaluations with 55% of patients having at least 3 evaluations performed. A model containing all three biomarkers revealed a significant, independent association between NT-proBNP and all the echocardiographic parameters, including LVEF (Beta coefficient per doubling of NT-proBNP [95% CI]: −0.12 [−0.16; −0.07] log2 (%EF), p<0.0001); mitral E/e' (0.17 [0.09; 0.24] log2 (change in ratio), p<0.0001); mitral E/A (0.22 [0.13; 0.30] log2 (change in ratio), p<0.0001); TAPSE (−0.06 [−0.11; −0.02] log2(mm), p=0.008), tricuspid regurgitation gradient (0.13 [0.07; 0.20] log2(mmHg), p=0.0001) as well as left ventricular and left atrial dimensions (p<0.001). Hs-TnT and CRP showed significant associations with some echocardiographic parameters after adjustment for clinical covariates, but associations lost significance after correction for the other biomarkers. Figure 1. Associations between repeatedly measured NT-proBNP and repeatedly measured echocardiographic parameters (Panel A). Temporal evolution of echocardiographic parameters (B) and biomarker levels (C). Conclusion Serum NT-proBNP independently reflects temporal changes in echocardiographic parameters of systolic and diastolic function, left ventricular filling pressure, estimated pulmonary pressure and chamber diameters. Our results support further studies on NT-proBNP as a surrogate marker for hemodynamic congestion and herewith support its potential value for therapy guidance. Acknowledgement/Funding The Bio-SHiFT study was supported by the Jaap Schouten Foundation (Rotterdam, the Netherlands) and the Noordwest Academie (Alkmaar, the Netherlands).


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Scott W Sharkey ◽  
Denise C Windenburg ◽  
Robert G Hauser ◽  
John R Lesser ◽  
Barry J Maron

Stress cardiomyopathy (SC) is a newly reported condition of older women, triggered by emotionally and physically stressful events, characterized by acute heart failure with a distinctive angiographic profile, and regarded as a reversible process. To date, extended follow-up of SC patients is largely unavailable. We have assembled a substantial consecutive group of patients with SC to assess short and long-term clinical consequences of this condition. Between 2001–2008, we prospectively identified and followed (mean 2.0 years, range 0–6.7) 113 consecutive women with SC at a tertiary care United States hospital. Patients were female, aged 32–92 years (mean 68±13), and 16 (14%) were < 55 years. In 105 (93%) a triggering stressful event (emotional in 50, acute illness in 55) was identified; however, in 8 patients (7%) no such event preceded SC. The ECG showed ST-segment elevation in 58(51%) patients and ejection fraction (EF) was 31±11%. Troponin was elevated in 109 (96%); peak troponin (T) was 0.64±0.76 ng/ml. Of the 113 patients, 110(97%) survived the acute event: 3 patients (3%) died in-hospital (cardiogenic shock in 2; subarachnoid hemorrhage in 1). Other complications included: cardiac arrest 2 (2%), hypotension requiring inotropic drug and/or intra-aortic balloon pump in 22 (19%), pulmonary or cerebral embolism in 3 (3%), left ventricular (LV) or right ventricular thrombus in 7 (6%) and LV outflow obstruction in 13 (12%). CMR findings included absent delayed hyperenhancement (gadolinium) in 82/83 (99%), normal LV apical contraction in 46%, RV akinesia in 22%, and pleural effusions due to heart failure in 46%. At follow-up, EF returned to normal in all patients, but one or more SC events recurred in 7 (6%) patients (complicated by non-fatal cardiac arrest in 1), of whom 3 were taking beta-blockers. Post-hospital death occurred in 15 (13%) patients of which 14 were noncardiac and 1 of unknown cause. Among this large cohort of women, some SC events occurred atypically either without a stress trigger or in younger premenopausal patients. SC also led to death in the acute phase or to later non-fatal recurrences of SC or cardiac arrest in about 10%. Therefore, the clinical profile of SC is much broader than previously regarded.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Alfonso Valle ◽  
Miguel Corbi ◽  
Mercedes Nadal ◽  
Jordi Estornell ◽  
Elena Lucas ◽  
...  

Background . In patients (pts) with chronic heart failure, late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) is capable to distinguish left ventricular systolic dysfunction (LVSD) related or not to coronary artery disease (CAD). Moreover about 10% of pts with dilated cardiomyopathy (DCM) are actually «unrecognized » ischemic cardiomyopathy (ICM), possibly because of coronary recanalization after silent infarction. However, the prognostic implications of « unrecognized » ICM are not known. Methods. Three hundred consecutive pts with heart failure and LVSD underwent LGE-CMR and were followed prospectively during 833 days (12–2724). The primary endpoint was the composite of cardiac death or heart failure hospitalization. Pts were classified into 4 groups : DCM without LGE (N 149) ; DCM with midwall fibrosis (n 35) ; ICM : ischemic scar and CAD (n 81) ; « unrecognized » ICM : ischemic scar without CAD (n 30). Results. 111 pts (38%) experienced events during follow-up.. There were non significant differences in event rate in patients with « unrecognized » ICM and ICM (53% and 63% respectively). By contrast the event rate in ICM groups were significantly higher than in pts with DCM (29% in group 1 and 31% in group 2 ; p = 0.000001) (Figure ). By multivariate analysis LGE was the strongest predictor of cardiac events (HR 1,7 CI 95% 1.07–2.88). Conclusions . In our series, pts with « unrecognized » ICM detected by CMR had a high risk of cardiac events during follow up similar to those pts with ICM. These findings had potentially important implications for routine use of CMR as a diagnostic and prognostic tool in patients with heart failure and systolic dysfunction.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Ibrahim Ali ◽  
Philip A Kalra

Abstract Background and Aims Best practice for treatment of patients with chronic heart failure involves beta-blockers and renin-angiotensin-aldosterone system inhibitors (RAASi) such as ACE inhibitors (ACE-i), angiotensin receptor blockers (ARB), mineralocorticoid antagonists (MRA) and neprolysin inhibitor/ARB. However, use of these agents, and optimisation of their dosage, is frequently limited by hyperkalaemia, the incidence of which is increased by the co-prevalence of chronic kidney disease (CKD). Management of patients in a bespoke Hyperkalaemia Clinic can be advantageous in facilitating optimal use of RAASi. Method A Hyperkalaemia Clinic was opened in July 2019 in this tertiary renal centre within an NHS trust that hosts 4 district hospital heart failure services. Referrals of patients with left ventricular systolic dysfunction whose RAASi could not be optimised because of hyperkalaemia were encouraged from heart failure specialist nurses and cardiologists. Management of the patients incorporated commencement of patiromer at 8.4g daily and increases in RAASi was usually devolved to the referring team. This report describes the activity and short-term outcomes of the first 17 months after opening of the clinic (follow up until 1st January 2021). Results 34 patients with systolic heart failure and problems with RAASi-associated hyperkalaemia were referred to the clinic. Mean age was 74 (range 44-88) years, 28% had stage 3a, 28% 3b and 8% stage 4 CKD. ACE-I or ARB were being used in 73% of patients at referral, 73% were using beta blockers and 50% MRA with loop diuretic use in 70%. At first visit 64% had normokalaemia, and 36% serum potassium 5.4-6.0 mmol/L. During follow-up, 6 (18%) patients discontinued patiromer due to gastrointestinal side effects, 3 no longer required the binder because of decrease in RAASi use and 2 patients died (one each from stroke and sepsis). One patient was switched to an alternative potassium binder. As of 1st January 2021, patiromer was still being administered to 22 (65%) patients, 8 of which had received this for &gt;12 months; all patients remained normokalaemic and none of them required magnesium supplementation. An increase in RAASi therapy had occurred in only 12 (35%) patients. Conclusion Our experience demonstrates the relative simplicity of managing hyperkalaemia via a bespoke clinic in cardio-renal patients. As this was nephrology-led, optimised management was dependent upon the assertive and collaborative involvement of the referring heart failure teams who helped with biochemical monitoring and alteration of RAASi therapy. However, less than half of the patients benefitted from an increase in RAASi therapy after normalisation of serum potassium, and there was definitely scope for improving this component of the care pathway via more direct multi-disciplinary interaction with the heart failure teams.


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