bluuebunny/crossref_metadata_2025 huggingface dataset:
Tricuspid regurgitation: long-term management, morbidity and mortality
Authors: Marquez Camas P , Rodriguez Capitan J , Chaparro Munoz M , Lopez Haldon J , Manovel Sanchez A , Becerra Munoz V.M , Doncel Abad V , Melgar Melgar A , Robles Mezcua A , Jimenez Navarro M
Published: November 2020

Introduction

The natural history of tricuspid regurgitation (TR) is poorly known and its morbi-mortality has been rarely described.

Objectives

Several causes lead to the appearance of TR. The aim of our study was to assess the prognosis of our patients taking into account the etiology and severity of their valvulopathy. We also wanted to evaluate the income-free survival.

Methods

We designed a bi-centre (including a tertiary-level hospital and a secondary hospital), descriptive and retrospective study that included 745 patients with at least moderate-to-severe TR who had not had any previous cardiac surgery for this pathology. Once patients were selected, clinical characteristics (age, sex, cardiovascular risk factors) as well as associated pathology, readmissions because of heart failure and mortality were evaluated.

Results

745 patiens were included in the study (70.7% women) from the year 2002 to the 2017. The age average was 72.28 years old (in a range of 16–97). The obtained frequency of primary TR (caused by an abnormality of any of the components of the TV apparatus) was 6.4%, secondary TR (due left-sided valvular and myocardial diseas, Pulmonary hypertension or increased RV afterload) was 67.6%, related to AF 19% and isolated TR 7%. After a long follow-up (global median survival 51.51 months) only 62 patients received surgical treatment. Figures 1–4 show survival curves depending on etiology. Figure 5 compares survival curves depending on sex characteristics.

Conclusions

TR (moderate-to-severe or more) was associated with poor outcomes from the beginning of the follow-up. This poor clinical prognosis was observed in all ethiological groups analyzed and in both genders.

Survival curves Tricuspid Regurgitation

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Sociedad Andaluza de Cardiología
Hemoglobin level at stabilization is associated with long-term all-cause mortality in patients with left-sided endocarditis, a POET substudy
Authors: Pries-Heje M , Hasselbalch R.B , Ihleman N , Gill S , Bruun N.E , Elming H , Jensen K , Oestergaard L , Helweg-Larsen J , Fosboel E.L , Koeber L , Toender N , Moser C , Iversen K , Bundgaard H
Published: November 2020

Background

Left-sided infectious endocarditis (IE) has a high 1-year mortality. Anemia is a common finding in patients with IE, yet little is known about frequency, severity, and associated outcomes in this setting.

Purpose

To examine the relationship between Hemoglobin (Hgb) level measured at IE stabilization (time of randomization) in the Partial Oral versus intravenous Antibiotic Treatment of Endocarditis (POET) trial - and long-term all-cause mortality.

Methods

In the POET trial, 400 patients with left-sided IE were randomized, after medical and/or surgical stabilization, to conventional antibiotic treatment or partial oral treatment. Only non-surgically treated patients were considered in this study. Patients were divided by quartiles into four groups based on Hgb level at randomization.

Results

We examined 248 patients with non-surgically treated IE. Median time from diagnosis of IE to randomization was 14 days (IQ 12–19). At long-term follow-up (median 3.2 years, IQ 2.18–4.60), 71 patients had died (28.6%). Patients in the lowest quantile (Hgb ≤6.0 mmol) had a HR of 4.17 (95% CI 1.81–9.61, p<0.001) for death compared to patients in the highest quantile (Hgb >7.5 mmol/L). This association remained significant after multivariable adjustment for age, sex, renal disease, C-Reactive Protein, and Prosthetic heart valve (HR 2.69, 95% CI 1.11–6.50); p=0.028).

Conclusion

Low Hemoglobin level at stabilization in patients with IE was associated with an increased risk of long-term mortality. Whether intensified treatment of anemia in patients with IE could improve long-term outcome requires investigation.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): The Danish Heart Foundation, The Capital Regions Research Council
Age differences in mortality in patients undergoing surgery for infective endocarditis
Authors: Ostergaard L , Smerup M.H , Iversen K , Jensen A.D , Dahl A , Chamat S , Eske Bruun N , Butt J.H , Bundgaard H , Torp-Pedersen C , Kober L , Fosbol E.L
Published: November 2020

Background

Infective endocarditis (IE) is associated with high mortality. Surgery may improve survival, but the intercept between benefit and harm is hard to balance and may be closely related to age.

Purpose

To examine the in-hospital and 90-day mortality in patients undergoing surgery for IE and to identify differences between age groups and type of valvular intervention.

Methods

By crosslinking nationwide Danish registries we identified patients with first-time IE undergoing surgical treatment in the period from 2000 to 2017. The study population was grouped in patients <60 years, 60–75 years, and ≥75 years of age. High-risk subgroups by age and surgical valve intervention (mitral vs aortic vs mitral+aortic) during IE admission were examined. Kaplan Meier estimates was used to identify 90-day mortality by age groups and multivariable adjusted Cox proportional hazard analysis was used to examine factors associated with 90-day mortality.

Results

We included 1,767 patients with IE undergoing surgery, 735 patients <60 years (24.1% female), 766 patients 60–75 years (25.8% female), and 266 patients >75 years (36.1% female). The proportion of patients with IE undergoing surgery was 35.3%, 26.9%, and 9.1% for patients <60 years, 60–75 years, and >75 years, respectively. For patients with IE undergoing surgery, the in-hospital mortality was 6.4%, 13.6%, and 20.3% for patients <60 years, 60–75 years, and ≥75 years of age, respectively and mortality at 90 days were 7.5%, 13.9%, and 22.3%, respectively. Factors associated with an increased risk 90-day mortality were: mitral valve surgery and a combination of mitral and aortic valve surgery as compared with isolated aortic valve surgery, patients 60–75 years and >75 years as compared with patients aged <60 years, prosthetic heart valve prior to IE admission, and diabetes, Figure. Patients >75 years undergoing a combination of mitral and aortic valve surgery had an in-hospital mortality of 36.3%.

Conclusion

In patients undergoing surgery for IE, a stepwise increase in 90-day mortality was seen for age groups, highest among patients >75 years with a 90-day mortality of more than 20%. Patients undergoing mitral and combined mitral and aortic valve surgery as compared to isolated aortic valve surgery were associated with a higher mortality. These findings may be of importance for the management strategy of patients with IE.

Mortality risk

Funding Acknowledgement

Type of funding source: None
SHARPEN score accurately predict in-hospital mortality in infective endocarditis: a real-world validation study
Authors: Alves S.G , Filippini F.B , Dannenhauer G.P , Seroiska G , Birk L.F.S , Terra D.H , Pivatto Jr F , Miglioranza M
Published: November 2020

Background

Infective Endocarditis (IE) has impressive 30-day mortality of up to 30%. Prompt recognition of high-risk patients is required in order to optimize management and outcomes. The SHARPEN score was recently developed to predict intrahospital mortality in patients admitted due to IE, regardless of the need to undergo cardiac surgery. We aimed to evaluate the accuracy of the SHARPEN score to predict in-hospital mortality in comparison to Charlson Comorbidity Index (CCI).

Methods

Retrospective cohort of all consecutive adult admissions between 2000 and 2016 with diagnosis of definitive IE according to the Modified Duke Criteria. The SHARPEN score was applied comprising: Systolic blood pressure at presentation, Heart failure, Age, Raised creatinine, Pneumonia, Elevated peak CRP and Non-intravenous drug abuser. The CCI was applied to assess comorbidities. Accuracy in predict mortality was estimated with C-statistic. DeLong test was used to compare the areas under the curve (AUC). Survival probabilities were estimated by Kaplan-Meier method and differences between survival curves analyzed using the log-rank test. Multivariate analysis using Poisson Regression with robust variation was performed to determine independent predictors of in-hospital mortality.

Results

179 cases of IE were registered (70% male; 55±17 years-old) with an in-hospital mortality of 22%. Cardiac surgery was required in 68 (38%) of the patients. Calculated SHARPEM and CCI scores were 9 (7–11) and 3 (1–6) points respectively. SHARPEN was able to predict in-hospital mortality with an AUC of 0.76 (95% CI 0.7–0.8; p<0.001) and cut-off >10 points (Sen=69%; Sp=71%; PPV=40%; NPV=89%). Mortality was significant higher (40% vs 11%; p<0.001) in patients with SHARPEN >10 points (FIGURE). CCI had a similar AUC of 0.7 (95% CI 0.6 - 0.8; p<0.001) with SHARPEN (p=0.32). However, in a multivariate analysis, SHARPEN score >10 points a stronger predictor related with in-hospital mortality (OR 2.3; 95% CI 1.1 - 4.8; p=0.03) in comparison to CCI >3 points (OR 1.4; 95% CI 0.7–2.8; p=0.3).

Conclusion

SHARPEN score demonstrated a good accuracy in predict in-hospital mortality independently of other variables, with a high negative predictive value. These findings suggest that SHARPEN score may be useful to stratify high-risk IE patients in a clinical setting.

Funding Acknowledgement

Type of funding source: None
Prognostic benefit of urgent cardiac surgery in left-sided infective endocarditis
Authors: Garcia Granja P.E , Lopez J.A , Ladron R , Cabezon G , Vilacosta I , Dominguez F , Olmos C , Sarria C , Lopez I , Carrasco M , Garcia-Pavia P , San Roman A
Published: November 2020

Background

Cardiac surgery is required in approximately 50% of patients with left-sided infective endocarditis (IE) being a high-risk procedure specially during active phase of the disease.

Purpose

To evaluate the impact of cardiac surgery in the in-hospital mortality of left-sided IE.

Methods

We used a prospective cohort of consecutive patients with definite left-sided IE between 2000 and 2017 (n=1002). A predictive model of in-hospital mortality was derived by adding the variable cardiac surgery to the already published ENDOVAL score. The benefit of cardiac surgery was calculated with the mean difference between the risk of in-hospital mortality considering urgent surgery and considering no surgery for each patient.

Results

The predictive model showed good discriminative capacity with an area under the ROC curve of 0.861 (95% CI: 0.830 - 0.891) and a good calibration (p-value in the Hosmer-Lemeshow test of 0.353). Figure shows the in-hospital mortality prediction of each patient in case of no-surgery (orange), urgent surgery (yellow) or real decision (blue). Mean reduction of in-hospital mortality risk in case of surgery for patients with a theoretical risk of in-hospital mortality between 0–20% in absence of surgery was 3.2±1.6%. For patients with a theoretical risk between 20–40% in absence of surgery the mean reduction was 8.1±1.1%. For patients with a theoretical risk between 40–60% in absence of surgery the mean reduction was 10.7±0.3%. For patients with a theoretical risk between 60–80% in absence of surgery the mean reduction was 9.7±0.9%. For patients with a theoretical risk between 80–100% in absence of surgery the mean reduction was 4.6±2.1%.

Conclusion

Urgent cardiac surgery is a protective factor of in-hospital mortality for all patients with left-sided IE but especially for those with intermediate risk.

Figure 1

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Gerencia Regional de Salud, Junta de Castilla y Leόn
Two common echocardiographic variables to diagnose cardiac amyloidosis: the AMYLoidosis Index (AMYLI) score
Authors: Aimo A , Chubuchny V , Vergaro G , Fontana M , Nicol M , Cohen-Solal A , Castiglione V , Spini V , Giannoni A , Taddei C , Pasanisi E , Passino C , Emdin M
Published: November 2020

Background

Early diagnosis of cardiac amyloidosis (CA) is warranted to initiate specific treatment and improve outcome. The amyloid light chain (AL) and inferior wall thickness (IWT) scores have been proposed to assess patients referred by hematologists or with unexplained left ventricular (LV) hypertrophy, respectively. These scores are composed of 4 or 5 variables, respectively, including strain data, and no decisional cut-offs were introduced.

Methods

Based on 2 variables common to the AL and IWT scores, we defined a simple score named AMYLoidosis Index (AMYLI) as the product of relative wall thickness (RWT) and E/e' ratio, and assessed its diagnostic performance. Optimal rule-out cut-offs were searched as those with negative likelihood ratio (LR−) <0.1.

Results

In the derivation cohort (n=251), CA was ultimately diagnosed in 111 patients (44%). The 2.22 score value was selected as rule-out cut-off (LR- 0.0). In the hematology subset, AL CA was finally diagnosed in 32 patients (48%), with 2.36 as rule-out cut-off (LR− 0.0). In the hypertrophy subset, ATTR CA was diagnosed in 79 patients (43%), with 2.22 as best rule-out cut-off (LR− 0.0). In the validation cohort (n=691), where more patients were diagnosed with CA (94% and 68% in the hematology and in the hypertrophy subsets, respectively), the 2.22 rule-out cut-off had a LR− = ∞ (as no patient scoring <2.22 had CA). In the hematology and hypertrophy subsets, the 2.36 and 2.22 cut-offs were effective for ruling-out CA, with both LR− = ∞ (as no patient scoring <2.36 or 2.22, respectively, had CA).

Conclusions

The AMYLI score (RWT* E/e') is simpler than those proposed and similarly accurate. A 2.22 cut-off value excludes CA diagnosis in patients undergoing a diagnostic screening for CA, while a <2.36 and a <2.22 value may be better considered in the subsets with either blood dyscrasia or unexplained hypertrophy, respectively.

Funding Acknowledgement

Type of funding source: None
Clinical features, risk factors, and prognosis of anthracycline-induced cardiotoxicity in patients with malignant lymphoma who received a CHOP like regimen
Authors: Nakayama T , Oshima Y , Kusumoto S , Osaga S , Yamamoto J , Wakami K , Goto T , Sugiura T , Seo Y , Iida S , Ohte N
Published: November 2020

Background

Anthracycline-induced cardiotoxicity is a serious complication in patients with malignant lymphoma (ML) who received chemotherapy, which threatens life prognosis and quality of life of patients. However, incidence and risk factors of cardiotoxicity in patients with ML who undergo intensive chemotherapy which aims complete remission is not clarified. Furthermore, prognosis after cardiotoxicity and that after recovery from cardiotoxicity have not been elucidated.

Method

We screened 443 ML patients who received either rituximab (R)-CHOP or CHOP regimen between January 2008 and December 2017 at Nagoya City University Hospital. Two handled forty-four patients who underwent echocardiography before and after chemotherapy were enrolled and data were analyzed retrospectively. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF) of 10% or greater and an LVEF was below 50%. Partial recovery was defined as a 5% or more of increase in LVEF and an LVEF was ≥50% after cardiotoxicity. Complete recovery was defined as an increase in LVEF became more than 95% of the baseline value. Patient's basic characteristics, chemotherapeutic regimen, laboratory data, echocardiographic data, and prognosis were collected from the medical records by two cardiologists and two hematologists.

Result

At baseline, the median age was 71 years, the median cumulative dose of doxorubicin was 302 mg/m2 and the median LVEF was 69%. During the follow-up period, cardiotoxicity was observed in 52 out of 244 patients (21%), 30 patients (12%) had a symptomatic heart failure, and 5 patients died from cardiovascular cause. Thirty-five patients developed cardiotoxicity during the first year of chemotherapy. Multivariate analysis identified that only the baseline LVEF (HR 0.949, 95% CI 0.919–0.981, p=0.002) was an independent risk factor for cardiotoxicity. In our study, patients who received more than 200 mg/m2 of doxorubicin developed cardiotoxicity frequently. Among 52 patients who experienced cardiotoxicity, partial recovery and full recovery were observed in 18 (35%) and 4 (8%) patients, respectively. Four patients without recovery died due to heart failure and 1 patient with partial recovery died suddenly. Six out of 18 patients with partial recovery developed re-cardiotoxicity.

Conclusion

ML patients who undergo more than 200 mg/m2 of doxorubicin need a watchful follow-up. Only a baseline LVEF was an independent risk factor for cardiotoxicity. one third of patients with partial recovery developed re-cardiotoxicity.

Funding Acknowledgement

Type of funding source: None
Procalcitonin in myocarditis patients: role in aetiology identification and risk stratification
Authors: Peretto G , Villatore A , Sala S , Riccio A , Ripa M , Basso C , Della Bella P
Published: November 2020

Background

Procalcitonin (PCT) is an established predictor of bacterial infections and sepsis. However, PCT involvement in cardiovascular diseases has been scarcely investigated so far. In particular, no studies at all ever addressed the role of PCT in myocarditis patients.

We aimed at evaluating PCT in myocarditis patients, as a potential biomarker of: a) aetiologic diagnosis; b) prognosis.

Methods

A cohort of 130 consecutive patients with a novel diagnosis of myocarditis confirmed by both endomyocardial biopsy and cardiac magnetic resonance were included in the study. Patients with known bacterial infections or bacterial myocarditis were excluded (n=5). PCT concentration was measured on admission in all patients. Prospective follow-up (FU) was performed every 6 months up to 5 years.

Results

Of 125 patients analyzed (mean age 45±15 years, males 62%, mean LVEF 48±15%), 22 (18%) had fulminant myocarditis (FM). The remaining 103 cases had non-fulminant myocarditis (NFM), including infarct-like presentation and non-malignant arrhythmias. Aetiology was viral or virus-negative in 23 and 102 patients, respectively.

The mean PCT value was 0.44±0.18 mcg/ml, with no significant differences between viral and virus-negative myocarditis (0.43±0.19 vs. 0.44±0.18 mcg/ml, p=0.90).

Baseline PCT concentration was significantly higher in FM patients (0.69±0.21 vs. 0.39±0.16 mcg/ml, p=0.07). Consistently, PCT was higher in patients with LVEF <60% (0.51±0.20 vs. 0.30±0.14 mcg/ml, p=0.03) and in those with elevated (>400 pg/mL) NT-proBNP (0.55±0.19 vs. 0.36±0.17 mcg/ml, p=0.03). As for inflammatory biomarkers, patients with high ESR (>20 mm/h) had also higher PCT values (0.56±0.20 vs. 0.37±0.16 mcg/ml, p=0.03). By converse, no association was found between PCT and CRP abnormal values (p>0.05).

At univariate analysis, high PCT (≥0.20 mcg/ml) was predictive of heart failure recurrence (OR 2.77, 95% CI 1.18–6.48, p=0.02) or arrhythmic cardiac arrest (OR 3.22, 95% CI 1.19–8.71, p=0.02) by discharge, with overall hospitalization prolonged by 10±4 days (p<0.05). Furthermore, patients with high PCT were more prone to myocarditis recurrences (13/80 vs. 4/45, p=0.03) by 5-year FU.

Conclusions

In myocarditis patients, elevated PCT values at presentation are not associated with myocarditis aetiology. Nonetheless, PCT suggests a worse short-term clinical outcome, and also a higher risk of myocarditis recurrences at long-term FU.

Funding Acknowledgement

Type of funding source: None
Treatment of virus negative chronic myocarditis: long term follow-up of TIMIC trial
Authors: Chimenti C , Russo M.A , Frustaci A
Published: November 2020

Background

The TIMIC trial demonstrated the short term efficacy of immunosuppression (IMS) in virus-negative inflammatory cardiomyopathy. However long term outcome of patients responsive to this treatment is still unclear.

Purpose

To assess the long term outcome of patients enrolled in the TIMIC trial.

Methods

The 85 (51 M, 34 F, 42.7±14.7 years) patients with endomyocardial biopsy proven virus-negative chronic inflammatory cardiomyopathy, enrolled in the TIMIC trial and treated either with prednisone and azathioprine (prednisone 1mg kg–1 day–1 for 4 weeks followed by 0.33 mg kg–1 day–1 for 5 months and azathioprine 2 mg kg–1 day–1 for 6 months) or placebo for 6 months, were evaluated in a long-term follow-up of up to 18 years (mean 15.2±2.0 SD, range 12–18 ys). Patients treated with placebo at the end of the 6-month enrollment because of the lack of improvement received IMS for further 6 months.

Results

At 6 months' follow-up 89% patients showed a significant improvement of left ventricular ejection fraction compared to baseline (LVEF rising from 27.0±5.7 to 46.2±6.4, % p<0.001).

This improvement was maintained in the long term follow-up (LVEF 51.1±6.4%, p<0.001). Importantly, the 42 patients initially on placebo showed an improvement comparable to the branch on IMS either on short (EF from 27.7% to 46.8±6.2%) and on long term follow up (LVEF from 27.7% to 50.6±5.6%, p<0.001). Nine patients (11%) did not show a significant improvement of LVEF either at short and long term follow-up and among them 4 died and 2 had a cardiac transplantation. Five patients (5.8%) had a relapse of the cardiac inflammatory process that promptly responded to a new TIMIC dose treatment. Four of them (4F, 41.2±9.4 ys age) had concomitant autoimmune diseases and the relapse was within the first 2 years after IMS discontinuation. One patient (M, 56 ys) had a relapse after 10 years following a flu-like syndrome.

Conclusion

Immunosuppressive therapy of virus negative inflammatory cardiomyopathy warrants in susceptible patients a long term recovery of heart function with very low incidence of recurrences, that respond to a new TIMIC protocol dose treatment.

Long term efficacy of TIMIC-IMS therapy

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): AIFA
Baseline clinical features in a large-scale registration survey of patient with hypertrophic cardiomyopathy throughout Japan: J-HCM registry study
Authors: Kubo T , Takano H , Takayama M , Doi Y.L , Minami Y , Ebato M , Inomata T , Katoh T , Okamoto R , Chikamori T , Watanabe E , Furugen A , Maekwa Y , Shimizu W , Kitaoka H
Published: November 2020

Background

Hypertrophic cardiomyopathy (HCM) is a most prevalent primary myocardial disorder with heterogeneous clinical features. However, there have been few studies on clinical features of HCM as a prospective cohort. In 2015, we established a large-scale registration survey of patients with HCM throughout Japan, named J-HCM registry study.

Purpose

The aim of this study was to clarify the clinical features of Japanese patients with HCM.

Methods

J-HCM registry study is a prospective, multicenter investigation, consisting of 24 hospitals. This time, we present the baseline clinical characteristics in this survey.

Results

Total 1484 patients were registered. The ages at registration and at diagnosis were 65±15 and 56±17 years, respectively, and 806 patients (54%) were men. Majority of the patients (95%) was NYHA class I or II. With regard to subtypes of HCM, there were 526 patients (36%) in the HCM with left ventricular (LV) outflow tract obstruction, 126 patients (8%) in the mid-ventricular obstruction, 57 patients (4%) in the end-stage phase characterized by LV ejection fraction <50%, and 197 patients (14%) in apical HCM. At registration, 80 patients (6%) had prior successful recovery from sustained ventricular tachycardia or ventricular fibrillation, 162 patients (11%) suffered from heart failure hospitalization, and 64 patients (4%) had history of embolic event. Regarding invasive treatment, 160 patients (10%) had prior septal reduction therapy and 162 patients (11%) had ICD implantation. According to the 2014 European Society of Cardiology Guidelines on sudden cardiac death (SCD) prevention, the study patients were divided into 3 categories by the HCM Risk-SCD calculator: patients distribution, 4% in the high risk group (≥6% calculated HCM Risk-SCD at 5 years), 7% in the intermediate risk group (4% to <6%), 69% in the low risk group (<4%), and 16% in the patients with extreme characteristics (Figure 1).

Conclusions

In this multicenter registration survey of patients with HCM, the baseline clinical characteristics were almost similar to several retrospective large-scale cohorts in Western countries except older age and less symptomatic state. This study will provide important knowledge regarding management of HCM.

Figure 1

Funding Acknowledgement

Type of funding source: None
Expression of miRNA-21 level in hypertrophic cardiomyopathy patients with chronic heart failure and preserved left ventricular ejection fraction: results of a 6-year follow-up
Authors: Davydova V , Bezhanishvili T.G , Filatova M.E , Andreeva S.E , Streltsova A.A , Poliakova A.A , Pyko S.A , Zaraiskii M.I , Gudkova A.Y.A
Published: November 2020

Introduction

Recently it is found that circulating miRNA-21 is associated with chronic heart failure (CHF) and ischemic heart disease. Its clinical significance in hypertrophic cardiomyopathy (HCM) and CHF with preserved left ventricular ejection fraction (LVEF) (≥50%) has to be investigated.

Purpose

The aim of this study was to analyze the expression of miRNA-21 in the peripheral blood of HCM patients and CHF with preserved LVEF (≥50%).

Materials and methods

From 2014 to 2019 years we examined 180 HCM patients. The study population consisted of 60 patients ≥19 years old (51.5 [36.2; 65.7]) with symptomatic HCM and CHF with preserved LVEF (≥50%). The diagnosis of HCM was established according to the guideline of the European society of cardiology on the diagnosis and treatment of HCM, 2014. The control group included 45 healthy donors without cardiovascular diseases and other severe pathologies, matched by age and sex with the studied group. Total RNA was extracted from plasma of patients. MiRNA-21 and reference RNA U6 cDNA was prepared based on StemLoop-technology. Expression was examined using semiquantitative RT-PCR protocol. Calculation of the relative gene expression level of miRNA-21 was done according to the standard procedure 2-ΔCt. IBM SPSS software package and Microsoft Excel 2010 were used for the statistical analysis of the collected data.

Results

The serum expression level of miRNA-21 in HCM patients (n=60) varied from 0.13 to 477.7 (4.92 [1.77; 13]) and was significantly higher than those in the control group (0.01 - 9.85 (0.84 [0.55; 1.23]), with statistically significant difference (p=0.001). The HCM group was divided according to CHF severity: I-II functional class (NYHA) (n=42) and III-IV functional class (NYHA) (n=18) subgroups. It was found a significant increase of expression microRNA-21 level in both subgroups HCM patients, compared with control group (p=0.001). The expression level of miRNA-21 also differed between HCM patients and CHF III-IV functional class (NYHA) vs those, who had CHF I-II functional class (NYHA) – 1.1–477.7 (13 [3.88; 41]) vs 0.1–119.4 (3.25 [1.41; 6.06]), respectively (p=0.003). In HCM patients and CHF III-IV functional class (NYHA) (n=18) the expression level of miRNA-21 positively correlated with LVEF (r=0.609; p<0.05).

Conclusion

HCM patients with CHF III-IV functional class (NYHA) and preserved LVEF (≥50%) demonstrated high expression level of miRNA-21.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Almazov Federal Medical Research Centre, Saint-Petersburg, Russian Federation, Pavlov University, L'va Tolstogo str. 6-8, Saint Petersburg, Russian Federation
The role of inflammation in recent-onset dilated cardiomyopathy
Authors: Chaloupka A , Krejci J , Poloczkova H , Hude P , Ozabalova E , Godava J , Zampachova V , Svobodova I , Kubanek M , Piherova L , Spinarova L
Published: November 2020

Background

The aetiology of recent-onset dilated cardiomyopathy (RODCM) includes inflammatory, genetic, toxic and metabolic causes. Delineating the role of inflammation on the genetic background could improve risk stratification.

Purpose

We aimed to ascertain the role of inflammation evaluated by serum CRP immunohistochemical and PCR analysis of endomyocardial biopsy (EMB) in conjunction with genetic testing in left ventricular reverse remodelling (LVRR) in 12-month follow-up.

Methods

83 RODCM patients enrolled in this prospective observational study underwent 12-month echocardiographic follow up whole-exome sequencing, and EMB. Presence of cardiotropic viruses was determined by PCR analysis of the EMB samples. Inflammation was defined according to TIMIC immunohistochemical criteria as the presence of >7 CD3+ lymphocytes/mm2 and/or >14 infiltrating leukocytes (LCA+ cells/mm2). LVRR was defined as an absolute increase in LV ejection fraction > +10% and a relative decrease of LV end-diastolic diameter >−10% at 12 months.

Results

LVRR occurred in 28 (34%) of all cases. PCR analysis uncovered cardiotropic viruses in 55 (66%) patients, with highest prevalence of parvovirus B19 (47%). (Figure 1) EMB analysis detected inflammation in 28 (34%) cases and inflammation significantly positively predicted LVRR (P=0.019). Sequencing identified disease-related gene variants (ACMG class 3–5) in 45 (54%) patients. Carriers of non-titin gene variants showed a lowest probability of 12-month LVRR (19%) P=0.041. Combination of genetic findings and inflammation did not improve the prediction of LVRR in 12 months. (Table 1)

Conclusion

Both myocardial inflammation and disease-causing variants can be identified in a large proportion of RODCM cases. Prognostic value of CRP and virus detection is low. Non-titin disease-related variants carriers of are less likely to reach LVRR. In contrast, myocardial inflammation detected by EMB predicts favourable remodelling in 12 months.

Figure 1

Funding Acknowledgement

Type of funding source: None
Impact of genetic reclassification on ARVC diagnosis based on the 2010 task force criteria
Authors: Costa S , Gasperetti A , Akdis D , Suna G , Medeiros Domingo A , Brunckhorst C , Duru F , Saguner A.M
Published: November 2020

Introduction

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited condition, which is associated with potentially life-threatening ventricular arrhythmias in the young. Approximately 60% of patients carry a possibly disease-causing genetic variant.

Purpose

The aim of this study was to investigate the impact of the 2015 American College of Medical Genetics (ACMG) Criteria on ARVC diagnosis based on the 2010 Modified Task Force Criteria (TFC).

Methods

The study included 79 patients from the Swiss ARVC Registry who harbored a genetic variant deemed to be associated with the disease at initial screening, and classified them as definite, borderline or possible ARVC. Every variant found was re-classified on Varsome Genetics, based on the 2015 ACMG Criteria. Clinical information was then assessed at last available follow-up of every patient and ARVC diagnosis was reclassified based on the newest genetic evidence available.

Results

In 42 out of 79 patients (53.2%), genetic variants were reclassified. Out of these, 33 variants (41.8%) were downgraded from pathogenic (P) / likely pathogenic (LP) to either variants of unknown significance (VUS) or benign (B) / likely benign (LB). Three patients (3.8%) were upgraded from VUS / LP to P. Out of the 12 variants initially classified as VUS, 9 (75%) were reclassified as B or LB. Overall, 13 patients (16.5%) were downgraded from their initial diagnosis (11 from definite to borderline and 2 from borderline to possible).

Conclusion

A significant proportion of patients with ARVC diagnosed based on the 2010 TFC were reclassified when the 2015 ACMG Criteria were taken into consideration. These findings may have clinical consequences, particularly for genetic cascade screening of family members of ARVC patients and necessitate reassessment of genetic variants of index patients who were previously diagnosed with ARVC.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): University Hospital Zurich
Filmin-c mutations in arrhythmogenic cardiomyopathy: a peculiar association with left dominat variant and high risk of sudden death
Authors: Bariani R , Celeghin R , Bueno Marinas M , Cason M , Cipiriani A , Rigato I , Pilichou K , Basso C , Perazzolo Marra M , Bauce B
Published: November 2020

Introduction

Arrhythmogenic cardiomyopathy (AC) is characterized by myocyte necrosis and progressive fibro-fatty substitution. Recently, truncated mutations on Filamin C gene have been correlated with AC and a peculiar phenotype characterized by a prominent left ventricular fibrosis and high risk of sudden death.

Purpose

To evaluate clinical and instrumental features of subjects affected by AC in whom genetic study identified presence of truncating and missense mutations on FLNC gene.

Materials and methods

A population of 192 probands affected by AC according to 2010 Task Force Criteria or McKenna's proposed criteria for left dominant AC were evaluated for FLNC variants. In positive probands and families anamnestic and clinical data (ECG, echocardiographic and cardiac magnetic resonance (CMR), twenty-four-hours ECG monitoring) were evaluated.

Results

A total of 19 subjects (9 probands and 10 family members) were identified as carrier of nine different FLNC mutations (5 truncating and 4 missense). In 3 patients (23%) clinical onset was characterized by major arrhythmic episodes and in one (8%) by sudden death. In 6 (46%) ECG was unremarkable and the most common abnormalities were low QRS voltages in peripheral leads (85%), followed by T wave inversion in lateral (15%) and in inferior leads (16%). Twenty-four-hours ECG monitoring revealed a high arrhythmic burden (PVC >500/die) in 6 cases (46%). CMR was performed in all patients. Four of them (31%) showed a LV dilatation, while in 2 cases (15%) a RV dilatation was present. In 8 (61%) a fatty infiltration was detected mainly affecting the left ventricle (6 cases, 46%). Moreover, late enhancement was present in 8 cases (62%), with a LV distribution.

Conclusions

This is the first studied population in which both truncating and missense variants were evaluated as causative of AC, confirming that FLNC gene mutations are rare (4% of probands without known AC causative mutations) and the prevalent clinical expression is a left dominant phenotype with a high degree of electrical instability and recurrence of sudden familial cardiac death.

Funding Acknowledgement

Type of funding source: None
Regression of cardiac amyloid deposits with novel therapeutics: reaching new frontiers in cardiac ATTR amyloidosis
Authors: Chacko L , Martinez-Naharro A , Kotecha T , Martone R , Hutt D , Lane T , Knight D , Moon J , Kellman P , Hawkins P , Gillmore J , Fontana M
Published: November 2020

Background

Cardiac involvement is the main driver of outcome in ATTR amyloidosis. Advances in therapeutics hold potential in transforming the course of the disease but the impact on cardiac amyloid load is unknown. The aim of this study was to evaluate the impact of patisiran, a new double stranded RNA based gene silencing therapy and a stabilizer, diflunisal, on cardiac amyloid load as measured by CMR and T1 mapping, in patients with ATTR amyloidosis.

Methods and results

Thirty-two patients with hereditary cardiac amyloidosis were studied. Sixteen patients received treatment with patisiran, and sixteen control subjects did not receive any disease modifying treatment. Patients were assessed with echocardiogram, CMR, NT-proBNP and six-minute walk time measurements at baseline and at 1 year (Mean interval 11.45±3.08 months in treatment group, mean interval 12.82±5.06 months in the control group). CMR analysis comprised LV volumes, T1 mapping to measure the extracellular volume (ECV) occupied by amyloid, T2 mapping and late gadolinium enhancement imaging. At 1-year follow-up, there was a substantial reduction in cardiac amyloid burden, in keeping with cardiac amyloid regression in 45% of patients on treatment. Overall the treatment group showed a reduction in ECV at 1 year follow up compared to an increase in ECV at 1 year in the control group (−1.37%, 95% CI: −3.43 to 0.68% versus 5.02%, 95% CI: 2.86% to 7.18% respectively, p<0.001). The treatment group also showed an improvement in change in 6MWT at 1 year follow up compared to 6MWT at 1 year in the control group (−8.12 meters, 95% CI: −50.8 to 34.6 meters in the treatment group versus −132.27 meters, 95% CI: −216 to −48.6 meters in the control group, p=0.002). The treatment group showed a reduction in BNP at 1 year follow up compared to an increase in the control group (−567.87, 95% CI: −1288.90 to 153.15 in the treatment group versus 2004, 95% CI: 12.82 to 3995.45 in the control group, p<0.001). There was no significant difference from baseline and 1-year data between the control and treatment groups for the difference in echocardiographic parameters, native T1, T2. There was a significant reduction in the percentage of injected dose by 99Tc-DPD scintigraphy in treated patients at 1 year compared to baseline.

Conclusions

These findings provide the first compelling evidence of substantial cardiac amyloid regression in ATTR amyloidosis, as well as the potential for CMR to be used to track response in treated patients with ATTR cardiac amyloidosis. Combination therapy with transthyretin knock down and stabilizing agents may well be synergistic given enhanced stoichiometry of stabilizers in the face of much reduced plasma transthyretin concentration.

Funding Acknowledgement

Type of funding source: None
Glucocorticoid therapy rather than the inflammatory state is associated with pulmonary embolism and deep vein thrombosis in cardiac sarcoid
Authors: Kolluri N , Elwazir M , Rosenbaum A , Blauwet L , Abou Ezzeddine O , McBane R , Bois J
Published: November 2020

Background

Sarcoidosis is an infiltrative inflammatory condition affecting multiple organs, with cardiac involvement designated as cardiac sarcoidosis (CS). It has been proposed that inflammatory conditions like sarcoid increase the risk of venous thromboembolism (VTE), defined as pulmonary embolism (PE) and deep vein thrombosis (DVT) due to the hypercoagulable environment created by inflammation.

Purpose

Although previous studies have demonstrated an association with sarcoidosis and VTE, these studies failed to account for steroid use (crucial for sarcoid treatment) as an important confounder. Also, no major studies have been done previously assessing the risk of VTE in CS specifically. The objective of this investigation is to determine the association between CS, steroid treatment for CS, and VTE.

Methods

Patients referred to our institution with concern for sarcoid/CS were retrospectively assessed. Specific variables of interest including general baseline characteristics and those specific to CS were analyzed for their association with VTE development.

Results

Using Heart Rhythm Society guidelines, 649 patients were split into three categories: 235 with no sarcoid (NS), 91 with extra-cardiac sarcoid (ECS) only, and 323 with CS. In univariate analysis, 39 (12%) CS patients developed a PE vs 9 (4%) NS patients (OR 3.44, p=0.0003) and 44 (14%) CS patients developed DVT vs 18 (8%) NS patients (OR 1.90, p=0.02). In multivariate regression analysis however, neither CS nor ECS was an independent risk factor for VTE (p>0.05) but steroid use was a strong predictor of VTE (HR 3.12, p=0.007 for PE, HR 6.17, p<0.0001 for DVT). Also, steroid dose was found to be an independent predictor for both PE (p=0.001) and DVT (p=0.007) in a Cox proportionate hazards model (significance appeared at >17.5 mg daily on a receiver operating characteristic curve).

Conclusion

Contrary to previous studies, the current study found that neither sarcoidosis nor CS is an independent risk factor for VTE. Rather, steroid therapy for CS treatment leads to an increased prevalence of VTE, specifically at a dose above 17.5 mg daily. More research is required to clarify this relationship and assess the importance of steroid-sparing immunosuppressive therapy and potentially VTE prophylaxis in CS management.

Steroid use and time to PE/DVT

Funding Acknowledgement

Type of funding source: None
ARVC specific autoantibody identifies cardiac sarcoidosis and correlates with inflammation activity
Authors: Suna G , Kolios A , Chatterjee D , Fatah M , Gasperetti A , Steffel J , Ruschitzka F , Duru F , Hamilton R.M , Saguner A.M
Published: November 2020

Introduction

Cardiac sarcoidosis (CS) is an inflammatory granulomatous disease of unknown origin. CS and arrhythmogenic right ventricular cardiomyopathy (ARVC) are overlapping syndromes. With both, patients are at increased risk of ventricular arrhythmias and sudden cardiac death. However, the diagnosis of CS is challenging, especially in patients with no extracardiac involvement, but correct diagnosis has large therapeutic impact. Recently, a novel diagnostic autoantibody (anti-DSG2 Ab) was identified in ARVC. We sought to identify this antibody in CS patients and correlate its levels with inflammation activity using cardiac positron-emission-tomography (18-FDG-PET).

Methods

Recombinant human desmoglein-2 (DSG2) proteins on western blots were exposed to sera as well as purified IgG of 14 patients with sarcoidosis (all confirmed by histology) and 6 controls (1 ARVC patient (positive control) and 5 healthy control subjects (negative control)). Clinical patient characteristics were correlated to detected antibody intensity levels.

Results

The sarcoidosis cohort comprised 43% (6/14) male patients and the average age was 50±12 years. Anti-DSG2 Abs were identified in 43% (6/14) and were detected faintly (below cut off level) in 21% (3/14) of all sarcoidosis patients. Antibody was also present in the ARVC patient (1/1) and was absent in all control subjects (5/5). Myocardial inflammation was present in 18-FDG PET imaging in all CS patients with positive anti-DSG2 Abs, corresponding to an average SUV (standardized uptake value) of 8.1±4.2. In patients with faint or no antibody, the SUV values were significantly lower with 1.2±2.1 and 3.2±4.0, respectively (P=0.044, one-way ANOVA). The Pearson correlation coefficient (R) was 0.6 (P=0.037) for SUV vs. higher antibody levels assessed by pixel count of the western blot bands for purified IgG.

Conclusions

Anti-DSG2 Abs are not only a specific biomarker for ARVC, but are also found in CS, suggesting a similar pathophysiological mechanism in these overlapping syndromes, both involving cardiac inflammation and myocyte cell death. Moreover, antibody levels correlate with disease activity on cardiac PET imaging. Larger cohorts are necessary to confirm these findings.

Funding Acknowledgement

Type of funding source: None
Myocardial constructive work is impaired in cardiac amyloidosis, eases the differential diagnosis and predicts the prognosis among patients with left ventricular hypertrophy
Authors: Palmiero G , Rubino M , Monda E , Caiazza M , Pafundi P.C , Caso V.M , Pacileo G , Caso P , Limongelli G
Published: November 2020

Background

Myocardial Work (MW) is a novel non-invasive echocardiographic method for myocardial performance assessment. MW is abnormal in patients with many forms of left ventricular hypertrophy [hypertrophic cardiomyopathy (HCM), hypertensive cardiomyopathy (HypCM), aortic stenosis (AS)] while little is known about cardiac amyloidosis (CA).

Purpose

We aimed to evaluate the role of MW in myocardial performance assessment, diagnostic significance and prognostic relevance in CA patients.

Methods

25 patients with CA (10 AL pts and 15 ATTRwt pts) and 75 patients with LVH (25 HCM pts, 25 HypCMP pts, 25 pts mild AS pts) were enrolled. Beside routine measurements, deformation parameters [GLS (Global Longitudinal Strain), EFSR (Ejection Fraction on Strain Ratio), RRSR (Relative Regional Strain Ratio)], and MW parameters [MWI (Myocardial Work Index), GCW (Global Constructive Work), GWW (Global Wasted Work), GWE (Global Work Efficiency)] for LV function evaluation were analysed.

Results

LV and RV function evaluated with classical and novel parameters were significantly impaired in CA group (see table). Among all these parameters, GCW showed the best performance to discriminate CA from other forms of LVH (AUC 0.90; 95% CI: 0.80–0.99; P<0,0001), with a cut-off value <1141 mmHg% showing good sensitivity and specificity (90% and 82%, respectively). At Kaplan-Meier estimation of cardiovascular mortality there were 9 deaths in the CA group and none in LVH group, showed significantly higher mortality at follow-up (p=0,0001). At multivariate analysis GCW (β=1,006; 95% CI: 1,003–1,009; P<0,0001) was the only prognostic parameter associated with cardiovascular mortality.

Discussion

Myocardial performance was reduced in CA group. GCW was able to discriminate CA from other forms of LVH and showed to be an independent prognostic factor. In our pilot study GCW seems a promising novel diagnostic and prognostic factor in CA.

Kaplan-Meier curve

Funding Acknowledgement

Type of funding source: None
Clinical significance of controlling nutritional status score for predicting short-term clinical events in takotsubo syndrome: a multicenter study
Authors: Takahashi K , Sudo M , Ogaku A , Saito Y , Atsumi W , Sonoda K , Nomoto K , Tachibana E , Okumura Y
Published: November 2020

Background

The Controlling Nutritional Status (CONUT) score is well known as a marker of nutritional status. Previous studies have reported that CONUT score could predict a prognosis of acute or chronic heart failure, and infective endocarditis. Takotsubo syndrome (TTS) is said to have a relatively good prognosis, but some patients have a bad turning point in hospital stay. Lower systolic blood pressure on admission, history of diabetes mellitus, and β-blocker use before admission have been reported as predictors of in-hospital cardiac complications. However, the prognostic utility of CONUT score in TTS is unclear. The aim of study was to evaluate duration of hospital stay and short-term clinical events with CONUT score in TTS.

Methods

Seventy-nine TTS patients who were admitted to 3 medical centers in Japan between January 2011 and October 2019 were enrolled. The average age was 71.8±11.5 years old, and the prevalence of female sex was 81%. The CONUT score was calculated based on the serum albumin, total lymphocyte and total cholesterol on admission. We retrospectively investigated the association between the short-term clinical events and CONUT score. The duration of hospital stay was defined as the primely outcome, and all cause death and congestive heart failure in hospital stay as the secondary outcome.

Results

The average CONUT score was 3.7±3.0. A positive correlation was found between the CONUT score and the duration of hospital stay (r=0.56, p<0.01). Twenty (25.3%) patients suffered from clinical events (all cause death and congestive heart failure in hospital). Those patients with clinical events had significantly higher the CONUT score than those without (all cause death, 7.2±2.6 vs. 3.5±2.9, p<0.01, congestive heart failure, 5.3±3.4 vs. 3.3±2.8, p=0.02, composite clinical events, 5.8±3.2 vs. 3.0±2.6, p<0.01). ROC curve analysis revealed that the optimal cut-off value of the CONUT score for the prediction of composite clinical events was 4.0 (AUC: 0.75, sensitivity: 80%, Specificity: 64%). The patients with CONUT score of 4 or more (high COUNT score) were more prevalent in patients who experienced composite clinical events than in those who didn't (80% vs. 35.6%, p<0.01). The patients with a high CONUT score had a longer hospital stay and higher occurrence of composite clinical events than those with CONUT score less than 4 (respectively, 27.2±19.1 days vs. 13.8±8.3 days, p<0.01, 25.3% vs. 9.5%, p<0.01).

Conclusions

The CONUT score in TTS patients was strongly associated with the duration of hospital stay and clinical events in hospital. The CONUT score is a simple indicator that can be calculated with only three factors. Therefore, the CONUT score on admission may be useful for a predictor of short-term clinical events in TTS patients.

Funding Acknowledgement

Type of funding source: None