Significance of serum FGF-23 for risk assessment of contrast-associated acute kidney injury and clinical outcomes in patients undergoing coronary angiography

Background Fibroblast growth factor (FGF)-23 levels rise as kidney function declines. Whether elevated FGF-23 levels are associated with an increased risk for contrast-associated acute kidney injury (CA-AKI) and major adverse cardiovascular events (MACE) in patients undergoing coronary angiography remain uncertain. Methods In total, 492 patients receiving coronary angiography were enrolled. Their serum FGF-23 levels were measured before administration of contrast media. The occurrence of CA-AKI was defined as a rise in serum creatinine of 0.5 mg/dL or a 25% increase from the baseline value within 48 h after the procedure. All patients were followed up for at least 1 year or until the occurrence of MACE including death, nonfatal myocardial infarction (MI), and ischemic stroke. Results Overall, CA-AKI occurred in 41 (8.3%) patients. During a median follow-up of 2.6 years, there were 24 deaths, 3 nonfatal MIs, and 7 ischemic strokes. Compared with those in the lowest FGF-23 tertile, individuals in the highest FGF-23 tertile had a significantly higher incidence of CA-AKI (P < 0.001) and lower incidence of MACE-free survival (P = 0.001). In multivariate regression analysis, higher FGF-23 level was found to be independently associated with a graded risk for CA-AKI (OR per doubling, 1.90; 95% CI 1.48–2.44) and MACE (HR per doubling, 1.25; 95% CI 1.02–1.52). Conclusions Elevated FGF-23 levels were associated with an increased risk for CA-AKI and future MACE among patients undergoing coronary angiography. FGF-23 may play a role in early diagnosis of CA-AKI and predicting clinical outcomes after coronary angiography.

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Association of Early and Late Contrast-Associated Acute Kidney Injury and Long-Term Mortality in Patients Undergoing Coronary Angiography

Journal of Interventional Cardiology ◽

10.1155/2021/6641887 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Zhubin Lun ◽

Jin Liu ◽

Liwei Liu ◽

Jingjing Liang ◽

Guanzhong Chen ◽

...

Keyword(s):

Acute Kidney Injury ◽

Coronary Angiography ◽

Cox Regression ◽

Late Phase ◽

Kidney Injury ◽

Rank Test ◽

Preoperative Serum ◽

Increased Risk ◽

Long Term Mortality

Background. Contrast-associated acute kidney injury (CA-AKI) is a common complication in patients undergoing coronary angiography (CAG). However, few studies demonstrate the association between the prognosis and developed CA-AKI in the different periods after the operation. Methods. We retrospectively enrolled 3206 patients with preoperative serum creatinine (Scr) and at least twice SCr measurement after CAG. CA-AKI was defined as an increase ≥50% or ≥0.3 mg/dL from baseline in the 72 hours after the procedure. Early CA-AKI was defined as having the first increase in SCr within the early phase (<24 hours), and late CA-AKI was defined as an increase in SCr that occurred for the first time in the late phase (24–72 hours). The first endpoint of this study was long-term all-cause mortality. Kaplan–Meier analysis was used to count the cumulative mortality, and the log-rank test was used to assess differences between curves. Univariate and multivariate cox regression analyses were performed to assess whether patients who developed different type CA-AKI were at increased risk of long-term mortality. Results. The number of deaths in the 3 groups was 407 for normal (12.7%), 106 for early CA-AKI (32.7%) and 57 for late CA-AKI (17.7%), during a median follow-up period of 3.95 years. After adjusting for important clinical variables, early CA-AKI (HR = 1.33, 95% CI: 1.02–1.74, P = 0.038 ) was significantly associated with mortality, while late CA-AKI (HR = 0.92, 95% CI: 0.65–1.31, P = 0.633 ) was not. The same results were found in patients with coronary artery disease, chronic kidney disease, diabetes mellitus, and percutaneous coronary intervention. Conclusions. Early increases in Scr, i.e., early CA-AKI, have better predictive value for long-term mortality. Therefore, in clinical practice, physicians should pay more attention to patients with early renal injury related to long-term prognosis and give active treatment.

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Rhabdomyolysis in a Patient with Severe Hypothyroidism: A Case Report

10.21203/rs.3.rs-94141/v1 ◽

2020 ◽

Author(s):

Mikayla Welch ◽

Naser Gharaibeh

Keyword(s):

Acute Kidney Injury ◽

Weight Gain ◽

Statin Therapy ◽

Thyroid Disease ◽

Patient Adherence ◽

Positive Family History ◽

Kidney Injury ◽

Initial Visit ◽

Increased Risk

Abstract BackgroundHashimoto’s thyroiditis is typically diagnosed incidentally from elevated TSH or after evaluation of suggestive symptoms, including weight gain and fatigue. Rarely, patients present with an initial hyperthyroid state, Hashitoxicosis, that lasts weeks to months. Through a review of the current literature, it became apparent that this case is unique in several ways: the patient’s age, lack of comorbid conditions, the unique presentation of her thyroid disease, as well as the development of acute kidney injury while hospitalized.Case PresentationHere we present the case of a 26-year-old female who was referred to the Endocrinology office in July 2019 with symptoms of hyperthyroidism. She has a positive family history of Graves’ disease (GD) in her mother and thyroid malignancy in her maternal aunt. On her initial visit, TSH was suppressed, free thyroid hormones were increased, and both TPO and TSI antibodies were elevated. It was determined that this was likely a presentation of GD, and the patient was started on methimazole. She was instructed to follow-up every four weeks for monitoring of symptoms and labs. Three months following the initial visit, the patient failed to follow-up in office. During this time, she was seen by her primary care physician, diagnosed with hyperlipidemia, and started on statin therapy. One month later, on a subsequent follow-up with endocrinology, the patient complained of new onset back pain, muscle cramps, weight gain, and cold intolerance. She was sent to the emergency department for work-up. Evaluation revealed rhabdomyolysis in the setting of severe hypothyroidism, complicated by acute kidney injury. Her final diagnosis was found to be Hashitoxicosis with subsequent hypothyroidism.ConclusionsHyper- and hypothyroidism are two extremes on the spectrum of autoimmune thyroid disease, and the presentation can vary from patient-to-patient. Rarely, severe hypothyroidism can present with rhabdomyolysis with increased risk in patients on statin therapy. Thus, it is important to ensure patients are clinically and biochemically euthyroid prior to initiation of statin therapy. This case emphasizes the need for communication among physicians and the importance of patient adherence to treatment plans.

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Long-term consequences of acute kidney injury: a narrative review

Clinical Kidney Journal ◽

10.1093/ckj/sfaa177 ◽

2020 ◽

Author(s):

Joana Gameiro ◽

Filipe Marques ◽

José António Lopes

Keyword(s):

Acute Kidney Injury ◽

Patient Outcomes ◽

Kidney Injury ◽

Current Evidence ◽

Long Term Outcomes ◽

Increased Risk ◽

Follow Up Care ◽

Risk Of Progression

Abstract The incidence of acute kidney injury (AKI) has increased in the past decades. AKI complicates up to 15% of hospitalizations and can reach up to 50–60% in critically ill patients. Besides the short-term impact of AKI in patient outcomes, several studies report the association between AKI and adverse long-term outcomes, such as recurrent AKI episodes in 25–30% of cases, hospital re-admissions in up to 40% of patients, an increased risk of cardiovascular events, an increased risk of progression of chronic kidney disease (CKD) after AKI and a significantly increased long-term mortality. Despite the long-term impact of AKI, there are neither established guidelines on the follow-up care of AKI patients, nor treatment strategies to reduce the incidence of sequelae after AKI. Only a minority of patients have been referred to nephrology post-discharge care, despite the evidence of improved outcomes associated with nephrology referral by addressing cardiovascular risk and risk of progression to CKD. Indeed, AKI survivors should have specialized nephrology follow-up to assess kidney function after AKI, perform medication reconciliation, educate patients on nephrotoxic avoidance and implement strategies to prevent CKD progression. The authors provide a comprehensive review of the transition from AKI to CKD, analyse the current evidence on the long-term outcomes of AKI and describe predisposing risk factors, highlight the importance of follow-up care in these patients and describe the current therapeutic strategies which are being investigated on their impact in improving patient outcomes.

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Association between mineral and bone disorder in patients with acute kidney injury following cardiac surgery and adverse outcomes

BMC Nephrology ◽

10.1186/s12882-019-1572-y ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Tianye Yang ◽

Wenji Wang ◽

Xiao Tang ◽

Peng Shi ◽

Lulu Zhang ◽

...

Keyword(s):

Acute Kidney Injury ◽

Cardiac Surgery ◽

Clinical Outcomes ◽

Fibroblast Growth Factor 23 ◽

Kidney Injury ◽

Adverse Outcomes ◽

Tartrate Resistant Acid Phosphatase ◽

Mineral And Bone Disorder ◽

Bone Specific Alkaline Phosphatase ◽

Increased Risk

Abstract Background Numerous studies have evaluated the prevalence and importance of mineral and bone disorders among patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). However, little is known about dysregulated mineral and bone metabolism in acute kidney injury (AKI). Methods We evaluated the association between mineral and bone metabolites and clinical outcomes in 158 patients who underwent cardiac surgery and developed AKI between June 2014 and January 2016. The baseline characteristics of the patients were recorded, and the levels of mineral and bone metabolites, including calcium, phosphate, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25D), bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase 5b (TRACP-5b) and C-terminal fibroblast growth factor 23 (cFGF23) were measured within 12 h after establishing the clinical diagnosis. Results The serum phosphate, iPTH and cFGF23 levels were significantly associated with the 28-day mortality (phosphate: Hazard Ratio [HR] =2.620, 95% CI: 1.083 to 6.338, p = 0.035; iPTH: HR = 1.044, 95% CI: 1.001 to 1.090, p = 0.046; cFGF23: HR = 1.367, 95% CI: 1.168 to 1.599, p < 0.001). Moreover, higher serum cFGF23 and BAP levels were independently associated with an increased risk of adverse outcomes. Additionally, we found that the serum cFGF23 levels rose most significantly and were associated with the severity of AKI (P < 0.001). Conclusions Mineral and bone metabolites are dysregulated and are associated with adverse clinical outcomes among patients with AKI. Trial registration www.clinicaltrials.gov NCT 00953992. Registered 6 August 2009.

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Incidence of contrast-induced acute kidney injury in patients with acute mesenteric ischemia and identification of potential predictive factors

Vascular ◽

10.1177/17085381211050766 ◽

2021 ◽

pp. 170853812110507

Author(s):

Emmanuel Augène ◽

Fabien Lareyre ◽

Julien Chikande ◽

Lucas Guidi ◽

Grégoire Mutambayi ◽

...

Keyword(s):

Acute Kidney Injury ◽

Contrast Medium ◽

Predictive Factors ◽

Mesenteric Ischemia ◽

Kidney Injury ◽

Acute Mesenteric Ischemia ◽

Creatinine Concentration ◽

Increased Risk ◽

Significant Difference

Objective Contrast-enhanced computed tomography angiography (CTA) is commonly used to investigate acute abdominal conditions, but the risk of contrast-induced acute kidney injury (CI-AKI) has been poorly investigated in patients with acute mesenteric ischemia. The aim of the present study was to evaluate the incidence of CI-AKI in these patients and identify potential predictive factors. Methods Patients admitted for acute mesenteric ischemia who had a diagnostic CTA with contrast medium and a follow-up of creatinine concentration were retrospectively included. Results Among 53 patients included, 9 (16.9%) developed CI-AKI. The prevalence of chronic kidney disease did not differ significantly between those who developed CI-AKI and those who did not (33.3 vs 18.2%, p=.372). Plasma total bilirubin and conjugated bilirubin levels were significantly higher in patients who developed CI-AKI (17.5 vs 8.0 μmol/L, p=.013 and 8.0 vs 3.0 μmol/L, p=.031, respectively). The proportion of patients who had revascularization was similar between patients who developed CI-AKI and those who did not (11.1 vs 20.5%, p>.999). No significant difference was observed for 30-day mortality and all-cause mortality for a median follow-up of 168 days (22.2 vs 13.6%, p=.611; and 33.3 vs 61.4%, p=.153, respectively). Conclusion This study reports the incidence of CI-AKI in patients with acute mesenteric ischemia after diagnostic CTA with contrast medium. Plasma bilirubin levels were a predictive factor of CI-AKI in these patients. The administration of contrast media during revascularization was not associated with an increased risk of CI-AKI.

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Contrast-Induced Acute Kidney Injury and Risk of Adverse Clinical Outcomes After Coronary Angiography

Circulation Cardiovascular Interventions ◽

10.1161/circinterventions.112.974493 ◽

2013 ◽

Vol 6 (1) ◽

pp. 37-43 ◽

Cited By ~ 142

Author(s):

Matthew T. James ◽

Susan M. Samuel ◽

Megan A. Manning ◽

Marcello Tonelli ◽

William A. Ghali ◽

...

Keyword(s):

Acute Kidney Injury ◽

Coronary Angiography ◽

Clinical Outcomes ◽

Kidney Injury

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Risk factors, predictions, and progression of acute kidney injury in hospitalized COVID-19 patients: An observational retrospective cohort study

PLoS ONE ◽

10.1371/journal.pone.0257253 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0257253

Author(s):

Maryam N. Naser ◽

Rana Al-Ghatam ◽

Abdulla H. Darwish ◽

Manaf M. Alqahtani ◽

Hajar A. Alahmadi ◽

...

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Cohort Study ◽

Serum Albumin ◽

Troponin I ◽

Cardiac Injury ◽

Kidney Injury ◽

Multivariate Regression Analysis ◽

Observational Cohort

Objectives Studies have shown that acute kidney injury (AKI) occurrence post SARS-CoV-2 infection is complex and has a poor prognosis. Therefore, more studies are needed to understand the rate and the predications of AKI involvement among hospitalized COVID-19 patients and AKI’s impact on prognosis while under different types of medications. Patients and methods This study is a retrospective observational cohort study conducted at Bahrain Defence Force (BDF) Royal Medical Services. Medical records of COVID-19 patients admitted to BDF hospital, treated, and followed up from April 2020 to October 2020 were retrieved. Data were analyzed using univariate and multivariate logistic regression with covariate adjustment, and the odds ratio (OR) and 95% confidence (95% CI) interval were reported. Results Among 353 patients admitted with COVID-19, 47.6% developed AKI. Overall, 51.8% of patients with AKI died compared to 2.2% of patients who did not develop AKI (p< 0.001 with OR 48.6 and 95% CI 17.2–136.9). Besides, deaths in patients classified with AKI staging were positively correlated and multivariate regression analysis revealed that moderate to severe hypoalbuminemia (<32 g/L) was independently correlated to death in AKI patients with an OR of 10.99 (CI 95% 4.1–29.3, p<0.001). In addition, 78.2% of the dead patients were on mechanical ventilation. Besides age as a predictor of AKI development, diabetes and hypertension were the major risk factors of AKI development (OR 2.04, p<0.01, and 0.05 for diabetes and hypertension, respectively). Also, two or more comorbidities substantially increased the risk of AKI development in COVID-19 patients. Furthermore, high levels upon hospital admission of D-Dimer, Troponin I, and ProBNP and low serum albumin were associated with AKI development. Lastly, patients taking ACEI/ARBs had less chance to develop AKI stage II/III with OR of 0.19–0.27 (p<0.05–0.01). Conclusions The incidence of AKI in hospitalized COVID-19 patients and the mortality rate among AKI patients were high and correlated with AKI staging. Furthermore, laboratory testing for serum albumin, hypercoagulability and cardiac injury markers maybe indicative for AKI development. Therefore, clinicians should be mandated to perform such tests on admission and follow-up in hospitalized patients.

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Incidence, Outcomes and Predictors of Acute Kidney Injury Post Allogeneic Stem Cell Transplant

Blood ◽

10.1182/blood-2020-136746 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 16-17

Author(s):

Kayla Madsen ◽

Gabrielle Cote ◽

Karyne Pelletier ◽

Abhijat Kitchlu ◽

Shiyi Chen ◽

...

Keyword(s):

Kidney Injury ◽

Multivariate Models ◽

Relapse Free Survival ◽

Advisory Committees ◽

Free Survival ◽

Post Transplant ◽

Gvhd Prophylaxis ◽

Increased Risk ◽

Grade 3

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers cure for some patients with hematological diseases but is associated with significant risk of morbidity and mortality. Acute kidney injury (AKI) represents an important cause of post-transplant complications, often multifactorial in the unique setting of allo-HSCT. However, to date, there is limited information on the overall impact of AKI in this patient population. To address this, we retrospectively reviewed the effect of AKI on transplant outcomes at Princess Margaret Cancer Centre (PMCC). METHODS: The study included 408 patients transplanted at PMCC between January 2015-January 2018 for any indication, using either reduced intensity (RIC) or myeloablative conditioning (MAC). Median follow-up time was 23 months. AKI was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Demographics, clinical characteristics and transplant related variables were extracted from patient records and the institutional allo-HSCT database. Univariate and multivariate Cox proportional hazard models were used to examine associations between AKI and outcomes including overall survival (OS), relapse free survival (RFS), graft versus host disease (GVHD) and relapse-free survival (GRFS). Univariate and multivariate Fine and Gray competing risk models were used to examine the association between AKI and incidence of relapse, treatment related mortality (TRM), grade 2-4 acute GVHD (aGVHD), grade 3-4 aGVHD and moderate-severe chronic GVHD (cGVHD). Multivariate models were used to examine the association of AKI and outcomes of interest, while adjusting for potential risk factors. RESULTS: The overall incidence of AKI at 100 days was 64% (stage 1: 62.6%, stage 2: 22.5% and stage 3: 14.8%). Dialysis was required in 2% of these patients. Mean baseline eGFR in the AKI group was 94.4 mL/min/1.73m2 (IQR 42, 141) vs 96.9 mL/min/1.73m2 (IQR 45.7, 142.9) in the non-AKI group. Patient-related risk factors for development of AKI were age over 60 (p=0.001), male gender (p=0.05), diabetes (p=0.004) and hypertension (p=0.003). Transplant related characteristics associated with AKI were MAC conditioning (p=0.02), veno-occlusive disease (p<0.0001), BK viremia (p=0.01), thrombotic microangiopathy (p=0.009), bacterial infections (p=0.001) and more than two cytomegalovirus (CMV) reactivations (p=0.02). There was no difference in mean cyclosporine levels in the first 100 days between patients who developed AKI and those who did not (p=0.80). AKI was less common in patients who received GVHD prophylaxis with dual T-cell depletion (TCD) with anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) (p<0.001) than those who received alternative GVHD prophylaxis. In the univariate analyses, compared with patients who did not have AKI, those with AKI had inferior 2-y OS: 46% versus 63% (p=0.0004). AKI patients had lower 2-y GRFS (29% vs 45%, p=0.0002), higher 2-y TRM (31% versus 17%, p=0.0003), and higher incidence of day 100 grade 3-4 aGVHD (13% vs 6%, HR 2.18, 95% CI=1.18-4.01, p=0.01). In multivariate analysis, AKI was associated with decreased 2-y OS (HR= 1.36, 95% CI 1.00-1.65, p=0.048), 2-y GRFS (HR= 1.42, 95% CI 1.10-1.82, p=0.006), and increased risk of day 100 grade 3-4 aGVHD (HR= 1.93, 95% CI 1.04-3.58, p=0.03). There was an association between AKI and TRM, specifically in those patients with stage 2 (HR= 1.76, 95% CI 1.06-3.30, p=0.03) and stage 3 AKI (HR= 2.64, 95% CI 1.44-4.83, p=0.002) compared to no AKI. In multivariate models, there was no association between AKI and relapse (p=0.65), grade 2-4 aGVHD (p=0.7) or moderate-severe cGVHD (p=0.81). CONCLUSION: Patients who develop AKI within 100 days of transplant have lower OS, GRFS, and higher grade 3-4 aGVHD and TRM. The use of dual TCD for GVHD prophylaxis is associated with lower risk of AKI, suggesting this may be a favorable regimen for those at increased risk for AKI. Contrary to previously published literature, there was no difference in cyclosporine levels between the non-AKI and AKI groups, suggesting that it may not be a significant cause of AKI post-transplant. AKI was more common in patients who had multiple episodes of CMV reactivation, highlighting the importance of CMV prophylaxis. AKI patients require close follow up, preventative strategies and monitoring for new or progression of chronic kidney disease post transplant. Disclosures Madsen: Jazz Pharmaceuticals: Honoraria. Pelletier:Celgene: Honoraria; International Kidney and Monoclonal Gammopathy: Membership on an entity's Board of Directors or advisory committees. Mattsson:Jazz Pharmaceuticals: Honoraria; ITB: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Mallinkrodt: Honoraria; Gilead: Honoraria.

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Associations of serum sodium levels with mortality in very elderly acute kidney injury patients

10.21203/rs.3.rs-16898/v1 ◽

2020 ◽

Author(s):

Qinglin Li ◽

Liang Pan ◽

Zhi Mao ◽

Hongjun Kang ◽

Feihu Zhou

Keyword(s):

Acute Kidney Injury ◽

Elderly Patients ◽

Serum Sodium ◽

Kidney Injury ◽

Mortality Rates ◽

Very Elderly ◽

Adjusted Analysis ◽

Increased Risk ◽

All Cause Mortality

Abstract Background: Patients suffering from acute kidney injury (AKI) have been associated with impaired sodium. However, studies on the association of dysnatremia with all-cause mortality risk in AKI patients are particularly lacking. We examined the relationship between different levels of serum sodium and mortality among very elderly patients with AKI. Methods: We retrospectively enrolled very elderly patients (≥ 75 years) from Chinese PLA General Hospital from 2007, to 2018. All-cause mortality was examined according to eight predefined sodium levels: <130.0 mmol/L, 130.0–134.9 mmol/L, 135.0–137.9 mmol/L, 138.0–141.9 mmol/L, 142.0–144.9 mmol/L, 145.0–147.9 mmol/L, 148.0–151.9 mmol/L, and ≥152.0 mmol/L. We estimated the risk of all-cause mortality using a multivariable adjusted Cox proportional hazard model, with a normal serum potassium level of 135.0–137.9 mmol/L as a reference. Results: In total, 744 geriatric patients were suitable for the final evaluation. Among them, 260 (34.9%) died within 90 days; during the 1-year follow-up, 5 patients were lost to follow-up, and 383 (51.8%) died. After 90 days, the mortality rates in the eight strata were 36.1, 27.8, 19.6, 24.4, 30.7, 48.6, 52.8, and 57.7%, respectively. In the multivariable adjusted analysis, patients with sodium levels <130.0 mmol/L [hazard ratio (HR): 2.247; 95% confidence interval (CI): 1.117–4.521], from 142.0 to 144.9 mmol/L (HR: 1.964; 95% CI: 1.100–3.508), from 145.0 to 147.9 mmol/L (HR: 2.942; 95% CI: 1.693–5.114), from 148.0 to 151.9 mmol/L (HR: 3.455; 95% CI: 2.009–5.944), and ≥152.0 mmol/L (HR: 3.587; 95% CI: 2.151–5.983) had an increased risk of all-cause mortality. After 1 year, the mortality rates in the eight strata were 58.3, 47.8, 33.7, 38.9, 45.5, 64.3, 69.4, and 78.4%, respectively. In the multivariable adjusted analysis, patients with sodium levels <130.0 mmol/L (HR: 1.944; 95% CI: 1.125–3.360), from 142.0 to 144.9 mmol/L (HR: 1.681; 95% CI: 1.062–2.660), from 145.0 to 147.9 mmol/L (HR: 2.631; 95% CI: 1.683–4.112), from 148.0 to 151.9 mmol/L (HR: 2.411; 95% CI: 1.552–3.744), and ≥152.0 mmol/L (HR: 3.037; 95% CI: 2.021–4.563) had an increased risk of all-cause mortality. Conclusion: Sodium levels outside the interval of 130.0–141.9 mmol/L were associated with increased risks of 90-day mortality and 1-year mortality in very elderly AKI patients.

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P1774Genetic heterogeneity and clinical outcomes of non-compaction cardiomyopathy

European Heart Journal ◽

10.1093/eurheartj/ehz748.0526 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T Vaikhanskaya ◽

T V Kurushka ◽

L N Sivitskaya ◽

A Liaudanski ◽

N G Danilenko

Keyword(s):

Clinical Outcomes ◽

Neuromuscular Disorders ◽

Multivariate Regression Analysis ◽

Adverse Outcomes ◽

Significant Heterogeneity ◽

Successful Resuscitation ◽

Pathogenic Variants ◽

Increased Risk ◽

Composite Endpoints

Abstract The clinical outcomes of non-compaction cardiomyopathy (NCM) range from mild-symptomatic to progressive HF, arrhythmias, thromboembolism, and SCD. Objective The genetic spectrum and clinical outcomes of verified NCM were investigated. Methods The study enrolled 72 unrelated pts (aged 39.2±14.1 years; 43/59.7% male; LVEF 44.7±13.2%) with morphological signs of non-compaction myocardium, confirmed by any three accepted criteria: Echo (Jenni and Stöllberger), MRI (Petersen and Jacquier). During the follow-up 59,7±16,2 months, diagnosis of NCM has been revised by supporting diagnostic elements based on clinical evidence: a family history of cardiomyopathy, coexisting neuromuscular disorders, abnormal 12-lead ECG findings, presence of arrhythmias, heart failure or thromboembolic events. After exclusion 19 cases with isolated asymptomatic and reversible (athletic/peripartum) LVNC, a group (53 persons) for NGS (174 genes) was formed. All variants considered as pathogenic and likely pathogenic were confirmed by a Sanger sequencing. Results Forty-nine (likely) pathogenic variants were identified in 38/71,7% carriers (gene positive pts), including 27/50,9% pts with single variant and 11/20,8% pts with complex genotypes. The most prevalent mutations involved genes were TTNtv (11), MYBPC3 (8), LMNA (4), then MYH7 (3), and two each ILK, HCN4, LAMP2, RAF1, SDHA, RYR2. One mutation is found in the genes TAZ, HADHA, ACTC1, ACTN2, MYH6, DSP, SLC25A4, FBN1, BAG3, SCN5A, TBX20. Clinical features and adverse outcomes during follow-up were compared between groups of the gene-positive and gene-negative pts. Combined adverse clinical outcomes were taken as composite endpoints: death due to HF, SCD, HTx, life-threatening VTA (VT/VF, successful resuscitation, ICD discharges). To analyze composite endpoints, a multivariate regression analysis was performed with step-by-step exclusion. As a result, a prognostic model was constructed (R=0.89; R2=0.78; F=32.9; p<0.ehz748.05261) and independent predictors of adverse outcomes were identified: gene-positivity (β=0.45; p=0.ehz748.05261), 6MWT (β=−0.30; p=0.0002), PQ interval (β=0.23; p=0.0008), syncope history (β=0.29; p=0.ehz748.05263), mTWA (β=0.23; p=0.0005), LVDD (β=0.27; p=0.0001) and RVEF (β=−0.40; p=0.ehz748.05261). As a strongest factor of adverse outcome was gene-positivity, Kaplan-Meier survival curves were constructed. According to the Cox F-criterion (F=24.9) a high level of significance of differences to achieving combined endpoints in the groups (p=0.0001) was determined. Conclusions These results show that NCM is basically a genetic disease with significant heterogeneity and predominant TTNtv mutations; the patients with (likely) pathogenic variants have a worse prognosis with an increased risk for the composite end point of death, transplantation, and defibrillator implantation. Genetic evaluation is an important for prediction and subsequent management NCM pts considering genetic status.

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