Dilated cardiomyopathy caused by truncating titin variants: long-term outcomes, arrhythmias, response to treatment and sex differences

2020 ◽  
pp. jmedgenet-2020-107178
Author(s):  
Christoffer Rasmus Vissing ◽  
Torsten Bloch Rasmussen ◽  
Anne Mette Dybro ◽  
Morten Salling Olesen ◽  
Lisbeth Nørum Pedersen ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Dilated Cardiomyopathy ◽  
Ventricular Arrhythmias ◽  
Left Ventricular ◽  
Response To Treatment ◽  
Composite Outcome ◽  
Long Term Outcomes ◽  
Female Sex ◽  
Negative Predictor

BackgroundTruncating variants in titin (TTNtv) are the most common cause of dilated cardiomyopathy (DCM). We evaluated the genotype-phenotype correlation in TTNtv-DCM, with a special focus on long-term outcomes, arrhythmias, response to treatment and sex-related presentation.MethodsData on patient characteristics and outcomes were collected retrospectively from electronic health records of patients genotyped at two Danish heart transplantation centres.ResultsWe included 115 patients (66% men). At diagnosis of DCM, mean age was 46±13 years and left ventricular ejection fraction (LVEF) was 28%±13%. During a median follow-up of 7.9 years, 26% reached a composite outcome of left ventricular assist device implantation, heart transplantation or death. In 20% an arrhythmia preceded the DCM diagnosis. In total, 43% had atrial fibrillation (AF) and 23% had ventricular arrhythmias. Long-term left ventricular reverse remodelling (LVRR; LVEF increase ≥10% points or normalisation) was achieved in 58% and occurred more frequently in women (72% vs 51%, p=0.042).In multivariable proportional hazards analyses, occurrence of LVRR was a strong independent negative predictor of the composite outcome (HR: 0.05 (95% CI 0.02 to 0.14); p<0.001). Female sex independently predicted lower rates of ventricular arrhythmias (HR: 0.33 (95% CI 0.11 to 0.99); p=0.05), while the location of the TTNtv was not associated with cardiovascular outcomes.ConclusionDCM caused by TTNtv presented in midlife and was associated with a high burden of AF and ventricular arrhythmias, which often preceded DCM diagnosis. Furthermore, LVRR occurred in a high proportion of patients and was a strong negative predictor of the composite outcome. Female sex was positively associated with occurrence of LVRR and longer event-free survival.

P337Natural history, reversibility and arrhythmias associated with truncating titin variants in dilated cardiomyopathy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C R Vissing ◽  
T B Rasmussen ◽  
M S Olesen ◽  
L N Pedersen ◽  
A Dybro ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Medical Therapy ◽  
Ventricular Arrhythmias ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Reverse Remodeling ◽  
Absolute Increase ◽  
The Mean

Abstract Background Truncating genetic variants in titin (TTNtv) are identified in 15–25% of patients with primary dilated cardiomyopathy (DCM). Previous genotype/phenotype studies have reported conflicting results regarding disease severity and pathologic features associated with TTNtv. Purpose To investigate the natural history, reversibility and burden of arrhythmias associated with TTNtv in a Danish cohort with long-term follow-up. Methods Patients with DCM, recruited from two Danish tertiary centers, were included based on the presence of a TTNtv in a cardiac expressed titin exon. Data on patients' medical history including symptoms, demography, family history, comorbidities, treatment, ECG features, and echocardiograms were registered. Outcome data including all-cause mortality, need of heart transplantation (HTX) or left ventricular assist device (LVAD), and presence of ventricular and supraventricular arrhythmias were registered. Left ventricular reverse remodeling (LVRR) was defined as an absolute increase in left ventricular ejection fraction (LVEF) ≥10% points or normalization. Results A total of 104 patients (71 men, 69%; 72 probands) with definite TTNtv-DCM were included. The mean age at DCM diagnosis was (mean±SD) 45±13 years (43±13 for men; 49±14 for women, p<0.04) and median follow-up was 8.1 years. The mean LVEF was 28±13% at time of diagnosis (26±12% for men; 30±13% for women, p=0.173). During follow-up, 31 patients (30%; 24 men) died or needed HTX/LVAD. Medical therapy was associated with LVRR in 79% of patients 3.6 years after diagnosis. LVRR was maintained long-term in 64% of patients. Women had a better response to medical therapy compared to men (mean LVEF increase 19%; vs 15% in men, p<0.04). Atrial fibrillation/flutter was observed in 40% of patients and ventricular arrhythmias in 23% of patients. Men had an earlier occurrence of both supraventricular and ventricular arrhythmias (p=0.005) with half of the men having experienced an arrhythmia at the age of 54 years. Freedom from arrhythmias with age Conclusion TTNtv leads to a DCM phenotype associated with a marked gender-difference in age at DCM diagnosis and high burden of both supraventricular and ventricular arrhythmias. Importantly, the DCM-TTNtv phenotype was associated with a high degree of reversibility of systolic function following medical therapy.

Neonatal enteroviral myocarditis: a potentially devastating disease

2020 ◽  
pp. 57-72
Author(s):  
Grazia Delle Donne ◽  
Piers Daubeney
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Gold Standard ◽  
Gastrointestinal Symptoms ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Long Term Outcomes ◽  
Mild Heart Failure ◽  
Initial Episode

Myocarditis is the most common cause of dilated cardiomyopathy. Diagnosis can be challenging—the presentation can vary from mild heart failure to cardiogenic shock and is often preceded by respiratory or gastrointestinal symptoms. The aetiology is predominantly viral in childhood. The electrocardiogram, echocardiogram, and cardiac biomarkers all assist in making the diagnosis. There is an emerging role for cardiac magnetic resonance imaging as a diagnostic tool. Endocardial biopsy is the gold standard for the diagnosis, but the risk of the procedure often precludes its use in childhood. Treatment of myocarditis comprises standard heart failure management and, in the most severe cases, mechanical support and transplant. Overall, myocarditis has a better outcome than other causes of dilated cardiomyopathy. Surviving the initial episode is not assured but does lead to excellent long-term outcomes, both in terms of survival and recovery of left ventricular function.

scholarly journals Long term outcomes in left ventricular noncompaction

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
G Casas ◽  
J Limeres ◽  
G Oristrell ◽  
L Gutierrez ◽  
R Barriales ◽  
...  
Keyword(s):  
Cardiovascular Events ◽  
Ventricular Arrhythmias ◽  
Left Ventricular ◽  
Left Ventricular Noncompaction ◽  
Long Term Outcomes ◽  
End Points ◽  
Multicentric Study ◽  
Ventricular Noncompaction

Abstract Funding Acknowledgements Type of funding sources: None. Background Left ventricular noncompaction (LVNC) is a heterogeneous entity with a wide phenotypic expression. Risk factors have not been well established and prognostic stratification remains challenging. Objectives Describe long term outcomes of LVNC patients and determine predictors of cardiovascular events.  Methods   Prospective multicentric study of consecutive patients fulfilling imaging diangostic criteria for LVNC (Jenni echo criteria and Petersen CMR criteria). Demographic, ECG, imaging and genetic variables were collected. End points were heart failure (HF), ventricular arrhythmias (VA), systemic embolisms (SE) and all-cause death. Major adverse cardiovascular events (MACE) was the combination of the four previous end points. Results 585 patients from 12 referral centres were included from 2000 to 2018. Age at diagnosis was 45 ± 20 years, 334 (57%) were male, baseline LVEF was 48 ± 17% and 18% presented late gadolinium enhancement (LGE). During a median follow-up of 5.1 years (IQR 2.3-8.1), 110 (19%) patients presented HF, 87 (15%) VA, 18 (3%) SE and 34 (6%) died. MACE occurred in 223 (38%) patients. LVEF was independently associated with HF, VA, SE and MACE: HR were 1.08, 1.02, 1.04 and 1.02 respectively (all p &lt; 0.05). LGE was more frequent in patients with reduced LVEF (39 Vs 53%, p &lt; 0.001) and was associated with higher HF and VA risk in patients with LVEF &gt; 35% (HR 2.69 and 2.48 respectively, p &lt; 0.05) (Figure 1). Patients with a normal ECG, LVEF≥50%, no LGE and no family aggregation presented no MACE (0%) at long term follow-up. Among patients who underwent genetic testing (354, 61%), TTN variants and complex genotype (more than one variant) presented lower LVEF and higher HF risk. ACTC1 variants were associated with VA. Conclusions LVNC carries a high long term risk of heart faliure and ventricular arrhythmias. LVEF is the most important predictor and myocardial fibrosis is associated with increased risk in patients without severe systolic dysfunction. Genotype is a modifier of outcomes. These factors might be used to risk stratify LVNC patients. Abstract Figure. Kaplan Meier survival curves

scholarly journals Impact of left ventricular function on immediate and long-term outcomes after pericardiectomy in constrictive pericarditis

2008 ◽  
Vol 136 (5) ◽  
pp. 1136-1141 ◽  
Author(s):  
Jong-Won Ha ◽  
Jae K. Oh ◽  
Hartzell V. Schaff ◽  
Lieng H. Ling ◽  
Stuart T. Higano ◽  
...  
Keyword(s):  
Left Ventricular Function ◽  
Ventricular Function ◽  
Constrictive Pericarditis ◽  
Left Ventricular ◽  
Long Term Outcomes

scholarly journals Osteoporosis after heart transplantation with reference to immunosuppression and renal function

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
E L Lofdahl ◽  
G R Radegran
Keyword(s):  
Lumbar Spine ◽  
Femoral Neck ◽  
Heart Transplantation ◽  
Immunosuppressive Therapy ◽  
Kidney Function ◽  
Normal Kidney ◽  
Normal Kidney Function ◽  
Ckd Stage ◽  
Negative Predictor

Abstract Background Osteoporosis is commonly found in heart transplantation (HT) recipients, and may develop as an adverse effect of the immunosuppressive therapy, as well as be a consequence of factors associated with heart failure prior to HT. Chronic kidney disease (CKD) is furthermore, like osteoporosis, frequently found in the HT patient population, and may also arise as a side-effect of the immunosuppressive therapy. Aims and method We sought to describe the bone mineral density (BMD) evolution, predictors of osteoporosis, and survival, as well as incidence of osteoporosis in relation to CKD up to 10 years after HT. The project was conducted as a retrospective cohort study including patients who underwent HT at an age of at least 20 years between January 1988 and June 2016 at our center. The project was approved by the local ethics board (approval nos. 2010/114, 2011/777, 2014/92). Results Pre-transplant BMD was a negative predictor of osteoporosis during the first post-operative year, with a HR of 0.13 (95% CI 0.063; 0.26; P&lt;0.001) and 0.54 (95% CI 0.34; 0.85; P&lt;0.001) in the lumbar spine and femoral neck, respectively, adjusted for age, gender, BMI, and immunosuppressive therapy. Similarly, pre-transplant BMD was a negative predictor of osteoporosis also up to 10 years after HT, with a HR of 0.19 (95% CI 0.11; 0.32; P&lt;0.001) and 0.55 (95% CI 0.39; 0.78; P=0.001), in the lumbar spine and femoral neck, respectively, adjusted for age, gender, BMI, and immunosuppressive therapy. CKD stage 3 or worse before HT was associated with a greater gain in BMD after HT compared with CKD stage less than 3 or normal kidney function (−2.5% [−5.6; 0.6] versus −6.6% [−8.8;-4.5], P=0.029), and was not associated with osteoporosis (Figure 1). Also, the cumulative incidence of osteoporosis in the lumbar spine after HT was higher in the group with CKD stage less than 3 or normal kidney function. Conclusions The greatest drop in BMD occurs within the first year after HT. Short- and long-term incidence of osteoporosis is positively associated with pre-transplant bone strength, suggesting that early initiation of osteoporosis preventive treatment, pharmacologically and non-pharmacologically, may be beneficial in preventing long- and short-term fracture-related morbidity and morbidity after HT. Moreover, CKD stage 3 or worse before HT was associated with higher lumbar BMD after HT, and was not a predictor of osteoporosis. CKD stage less than 3 or normal kidney function before HT exhibited a greater BMD loss in the lumbar spine. Finally, the change in GFR during the first postoperative year was not associated with long-term BMD loss or osteoporosis. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Anna-Lisa & Sven-Erik Lundgren's Foundation and ALF's Foundations, Lund, Sweden Figure 1

scholarly journals Evaluation of different late left ventricular remodeling definitions for predicting long-term outcomes in acute myocardial infarction patients undergoing percutaneous coronary intervention

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Zhang ◽  
X Xie ◽  
C He ◽  
X Lin ◽  
M Luo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ventricular Remodeling ◽  
Cox Regression ◽  
Left Ventricular Remodeling ◽  
Left Ventricular ◽  
Long Term Outcomes ◽  
Cox Regression Analysis ◽  
Long Term Mortality

Abstract Background Late left ventricular remodeling (LLVR) after the index acute myocardial infarction (AMI) is a common complication, and is associated with poor outcome. However, the optimal definition of LLVR has been debated because of its different incidence and influence on prognosis. At present, there are limited data regarding the influence of different LLVR definitions on long-term outcomes in AMI patients undergoing percutaneous coronary intervention (PCI). Purpose To explore the impact of different definitions of LLVR on long-term mortality, re-hospitalization or an urgent visit for heart failure, and identify which definition was more suitable for predicting long-term outcomes in AMI patients undergoing PCI. Methods We prospectively observed 460 consenting first-time AMI patients undergoing PCI from January 2012 to December 2018. LLVR was defined as a ≥20% increase in left ventricular end-diastolic volume (LVEDV), or a &gt;15% increase in left ventricular end-systolic volume (LVESV) from the initial presentation to the 3–12 months follow-up, or left ventricular ejection fraction (LVEF) &lt;50% at follow up. These parameters of the cardiac structure and function were measuring through the thoracic echocardiography. The association of LLVR with long-term prognosis was investigated by Cox regression analysis. Results The incidence rate of LLVR was 38.1% (n=171). The occurrence of LLVR according to LVESV, LVEDV and LVEF definition were 26.6% (n=117), 31.9% (n=142) and 11.5% (n=51), respectively. During a median follow-up of 2 years, after adjusting other potential risk factors, multivariable Cox regression analysis revealed LLVR of LVESV definition [hazard ratio (HR): 2.50, 95% confidence interval (CI): 1.19–5.22, P=0.015], LLVR of LVEF definition (HR: 16.46, 95% CI: 6.96–38.92, P&lt;0.001) and LLVR of Mix definition (HR: 5.86, 95% CI: 2.45–14.04, P&lt;0.001) were risk factors for long-term mortality, re-hospitalization or an urgent visit for heart failure. But only LLVR of LVEF definition was a risk predictor for long-term mortality (HR: 6.84, 95% CI: 1.98–23.65, P=0.002). Conclusions LLVR defined by LVESV or LVEF may be more suitable for predicting long-term mortality, re-hospitalization or an urgent visit for heart failure in AMI patients undergoing PCI. However, only LLVR defined by LVEF could be used for predicting long-term mortality. FUNDunding Acknowledgement Type of funding sources: None. Association Between LLVR and outcomes Kaplan-Meier Estimates of the Mortality

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