bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic value of electrocardiograms to identify pericardial effusion in acute malaria: a cross-sectional study
Authors: Kaagaard M D , Matos L O , Wegener A , Holm A E , Gomes L C , Lima K O , Vieira I M , Souza R M , Marinho C F , Biering-Soerensen T , Silvestre O M , Brainin P
Published: October 2021

Background

Patients with acute malaria are at risk of pericarditis and may benefit from timely identification of pericardial effusion. However, diagnostic imaging tools, such as echocardiography, are not always available in malaria endemic regions.

Purpose

The aim of this study is to examine the diagnostic yield of pathology in electrocardiograms (ECG) to identify pericardial effusion in acute malaria.

Methods

We enrolled adult acute malaria patients in community healthcare clinics in a remote area in South America. All patients underwent ECG, echocardiography, and peripheral blood smears. We excluded patients on anti-malarial medication, suspected concomitant infection and pregnant women. All ECGs were examined for the following criteria: (i) PR-depression >0.5mm and/or ST-elevation 0.5–1mm (I, II, aVL, aVF, V2–6) (ii) PR-elevation >0.5mm (only aVR), (iii) ST/T-ratio >0.25 (only V6), (v) low voltage, defined as QRS amplitude <5 mm in limb leads or <10 mm in precordial leads, and (vi) Spodick's sign (all leads). A criterion was positive when present in ≥2 leads. Information on shortness of breath and/or chest pain was also collected. Pericardial effusion was diagnosed by echocardiography and had to be ≥0.5cm in width.

Results

We included 99 non-severe malaria patients (age 40±15 years, 55% men, median parasite density 1517/mm3, [interquartile range 528 to 6,585/mm3]) who suffered from Plasmodium vivax (n=75), falciparum (n=22 falciparum) and mixed vivax/falciparum (n=2). The ECGs showed a mean frequency of 78±16bpm, PR-interval 147±20ms, QRS 88±11ms and QT-interval 376±34ms. A total of 11 patients displayed pericardial effusion (mean width 0.9±0.3cm, n=7 vivax, n=2 falciparum, n=2 mixed). Patients with effusion were older (mean age 39 vs 53 years, P=0.003), but displayed no difference in sex, parasite density or parasite species compared to patients without pericardial effusion (P>0.05). Distribution of ECG findings and symptoms are displayed in figure 1A. PR-depression had a sensitivity and specificity for diagnosing pericardial effusion of 73% and 90%, respectively. The sensitivity and specificity for other ECG findings and clinical symptoms are displayed in Figure 1B.

Conclusion

ECG findings may aid in identifying pericardial effusion in acute malaria, specifically PR depression which had a diagnostic yield of 73% sensitivity and 90% specificity. Based on this, ECG in acute malaria may improve treatment and risk stratification when echocardiography is not an option.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation, Independent Research Fund Denmark ECG findings in malaria patients
Outcomes of trans-catheter versus surgical aortic valve replacement for patients with classic low-flow low-gradient aortic stenosis
Authors: Vandermolen S , Patel K P , Saberwal B , Cooper J , Pugliese F , Khanji M , Mullen M J , Ozkor M , Kennon S , Baumbach A , Awad W
Published: October 2021

Background

Classical low-flow low-gradient aortic stenosis (cLFLG-AS) is frequently encountered within clinical practice [1], and is often associated with high mortality [2]. Whilst aortic valve replacement can improve outcomes, there is a lack of real-world data guiding the decision between trans-catheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) in this specific patient cohort.

Purpose

To compare outcomes between TAVI and SAVR in patients with cLFLG-AS.

Methods

cLFLG-AS was defined by an aortic valve area <1cm2, mean gradient <40mmHg or peak velocity <4m/s and left ventricular ejection fraction <50%. All patients who met cLFLG-AS criteria who underwent TAVI or SAVR at our tertiary referral centre between 2015 and 2020 were included. Inverse probability weighting was used to adjust for differences in baseline characteristics and the non-random assignment of treatment modalities. The primary end-point was all-cause mortality. Secondary end-points were procedure-related permanent pacemaker implantation, renal replacement therapy (RRT) and stroke.

Results

322 patients were included (220 TAVI and 102 SAVR). Baseline characteristics were: male sex 70%, mean gradient 30mmHg (23–35), aortic valve area 0.8cm2 (0.6–0.9). Patients undergoing TAVI were older than the SAVR group (81.3±8.5 vs 70.6±11.1 years, p<0.0001) with higher Logistic Euroscore (19.3 (11.8–32.3) vs 7.1 (3.7–14.1), p<0.0001) (figure 1).

At median follow-up of 2.7 years (1.5–4.1), 99 patients had died; 70 (31.8%) had TAVI and 29 (28.4%) had SAVR. Both unweighted and weighted Kaplan-Meier curve analysis was performed; there was similar survival between SAVR and TAVI (log rank test 0=0.27 and p=0.4 respectively) (figure 2).

Adjusted hazard ratio (HR) for mortality with SAVR was 0.78 unweighted (95% CI 0.5–1.21; p=0.27) and 0.66 weighted (95% CI 0.26–1.64; p=0.37).

In terms of contributory procedural factors, concomitant multiple valve intervention in the SAVR group independently affected mortality (HR 5.47, 95% CI 2.52–11.51, p<0.001).

There was no difference in permanent pacemaker insertion or stroke across the two groups, but rates of RRT were higher in SAVR cohort (13.7% vs 0%, p<0.001).

Conclusions

Despite the TAVI cohort being both older and at higher risk, there was no observed difference in mortality between TAVI and SAVR in the mid-term. Deciding upon intervention choice can therefore be based upon criteria other than the specific presence of a classic low-flow low-gradient state.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Clinical training research fellowship from the British Heart Foundation Baseline characteristics by treatmentKaplan-Meier curves for TAVI vs SAVR
Association of left atrial volume index with outcomes after transcatheter mitral valve repair for secondary mitral regurgitation: results from the EuroSMR registry
Authors: Iliadis C , Kalbacher D , Lurz P , Petrescu A , Orban M , Karam N , Lubos E , Thiele H , Von Bardeleben S , Hausleiter J , Pfister R ,   EuroSMR
Published: October 2021

Background

The benefit of transcatheter edge-to-edge mitral valve repair (TMVr) in heart failure patients with secondary mitral regurgitation (SMR) shows large heterogeneity. A potential explanation might be the burden and chronicity of left-ventricular backward failure which is reflected by left atrial (LA) size.

Purpose

To investigate the role of LA volume index (LAVi) in real-world SMR patients undergoing TMVr.

Methods

SMR patients in a European multicenter registry were evaluated. Outcomes were evaluated according to LAVi at baseline. Main analysis was performed for all-cause mortality; residual mitral regurgitation, improvement of NYHA class and heart failure hospitalization were analyzed for patients available.

Results

823 included patients were divided according to LAVi into quintiles (≤42, 43–52, 53–62, 63–78, ≥79). A higher hazard for mortality occurred in the four upper quintiles compared to the lower quintile (HR [95% CI] 1.61 [1.08–2.4], 1.65 [1.11–2.46], 1.52 [1.02–2.26] and 1.35 [0.89–2.05]). The incidence of all-cause mortality per 100 patient-years was 14.6, 23, 23.9, 21.7 and 19.5, respectively. Consequently, a cut-off of 42ml/m2 was adopted, which was associated with a significantly higher hazard for mortality after a mean of 589 days (HR 1.54 [95%-CI 1.1–2.1], p=0.01). Technical success rate (postprocedural MR ≤2+) was higher in large LAVi group (95% vs. 91%, p=0.045). The endpoints of heart failure hospitalization, improvement of NYHA class were not different among groups. Multivariable Cox regression analysis including age, EF<30%, diabetes mellitus and NTproBNP showed LAVi >42ml/m2 to be an independent predictor of mortality.

Conclusion

LA dilatation defined by LAVi>42 ml/m2 was associated with higher mortality hazard in SMR patients undergoing TMVr after multivariable adjustment. Our findings warrant further study on whether timely TMVr intervention in patients with SMR and small LAVi can modify outcome.

Funding Acknowledgement

Type of funding sources: None.
External validation of the HCM Risk-Kids model for predicting sudden cardiac death in childhood hypertrophic cardiomyopathy
Authors: Norrish G , Qu C , Field E , Cervi E , Elliott P , Ho C , Omar R , Kaski J P ,   International Paediatric Hypertrophic Cardiomyopathy Consortium
Published: October 2021

Background

Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM). The newly developed HCM Risk-Kids model provides clinicians with individualised estimates of risk. The aim of this study was to externally validate the model in a large independent, multi-centre patient cohort.

Methods

A retrospective, longitudinal cohort of patients diagnosed with HCM aged 1–16 years independent of the HCM-Risk-Kids development and internal validation cohort was studied. Data on HCM Risk-Kids predictor variables (unexplained syncope, non-sustained ventricular tachycardia, maximal left ventricular wall-thickness, left atrial diameter and left ventricular outflow tract gradient) were collected from the time of baseline clinical evaluation. The performance of the HCM Risk-Kids model in predicting risk at 5 years was assessed.

Results

The cohort consisted of 421 patients with a median age at baseline evaluation of 12.3 years (IQR 7.3, 14.4). Over a median total follow up 3.48 years (IQR 1.83, 6.62, range 1 month – 20.7 years). Fourteen patients (3.3%) died and 10 (2.4%) underwent cardiac transplantation. Twenty-three patients (5.4%) met the SCD end-point within 5-years, with an overall incidence rate of 2.03 per 100 patient years (95% CI 1.48–2.78). Model validation showed a Harrell's C-index of 0.745 (95% CI 0.52–0.97) and Uno's C-index 0.714 (95% 0.58–0.85) with a calibration slope of 1.15 (95% 0.51–1.80). Figure 1a describes the agreement between predicted and observed 5-year cumulative proportion of SCD or equivalent events for each tertile of predicted risk in one imputed data set. One hundred and twenty-five (29.7%) patients had a predicted 5-year risk of ≥6%. SCD events occurred in 6 patients (2.0%) with a predicted risk <6% and 17 (13.6%) with a predicted risk ≥6. A 5-year predicted risk threshold of ≥6% identified 17 (73.9%) SCD-events with a corresponding C-statistic of 0.702 (95% CI 0.60–0.81) (Figure 1b).

Conclusions

This study reports the first external validation of the HCM Risk-Kids model in a large and geographically diverse patient population. A 5-year predicted risk of ≥6% identified over 70% of events, confirming that HCM Risk-Kids provides a method for individualised risk predictions and shared decision making in children with HCM. Incorporation of the model into routine clinical care will enable independent prospective model validation and assessment of the effect of its use in clinical practice.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart FoundationMedical Research Council Observed vs predicted risk by tertilesObserved vs predicted by threshold
Combination of arrhythmogenic right ventricular dysplasia with left ventricular non-compaction as a special form of cardiomyopathy: clinic, diagnostics, genetic, natural course
Authors: Lutokhina Y A , Blagova O V , Shestak A G , Polyak M E , Bukaeva A A , Zaklyazminskaya E V , Varionchik N V , Sedov V P , Kogan E A , Alexandrova S A , Nedostup A V
Published: October 2021

Background

A few cases of combination of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) with left ventricular noncompaction (LVNC) have been described.

Aims

To study the genetics, diagnostical features and clinical course of the combination of ARVC with LVNC.

Materials and methods

58 patients with ARVC diagnosis (26 men; mean age 39.1±14.2 years; mean follow-up period – 21.5 [6; 60] months) and 125 patients with LVNC (74 men; mean age 46.4±15.1 years; mean follow-up period – 14 [3; 40] months). All patients underwent electrocardiogram (ECG), echocardiography, 24-h ECG monitoring. Heart MRI was performed in 53 (91.4%) patients with ARVC and 60 (48%) with LVNC, heart CT – in 18 (31%) patients with ARVC and 89 (71.2%) with LVNC. For all patients with combination of ARVC and LVNC DNA-diagnostic was performed using both ARVC (PKP2, DSG2, DSP, DSC2, JUP, TMEM43, TGFB3, PLN, LMNA, DES, CTTNA3, EMD, SCN5A, LDB3, CRYAB, FLNC) and LVNC (MYH7, MYBPC3, TAZ, TPM1, LDB3, MYL2, MYL3, ACTC1, TNNT2, TNI3) gene panels.

Results

Combination of ARVC and LVNC was found in 9 patients (15.5% of patients form ARVC cohort and 7.2% from LVNC cohort). These patients were distinguished from patients with isolated ARVC or LVNC by aggressive ventricular arrhythmias (frequent premature ventricular beats, sustained ventricular tachycardia, significantly worse antiarrhythmic therapy effect, appropriate shocks of implanted cardioverter-defibrillators (ICD) in all patients with ICD). Patients with combination of ARVC+LVNC were also distinguished from patients with isolated LVNC by the dilatation of RV, low QRS voltage on ECG, presence of AV block, absence of signs of LV hypertrophy on ECG. LV dilatation with reduction of its ejection fraction distinguished patients with mixed cardiomyopathy from patients with isolated ARVC. Potentially pathogenic variants (IV-V classes of pathogenicity) and variants of unclear clinical significance (III class of pathogenicity) were found in both desmosomal and non-desmosomal genes in 78% of patients, including 3 (33%) in DSP gene.

Conclusions

The combination of ARVC and LVNC can be caused by mutations in both desmosomal and non-desmosomal genes and has typical features: aggressive, resistant ventricular rhythm abnormalities leading to appropriate ICD shocks and a high risk of sudden cardiac death.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Genetic testing of patients was supported by Grant No. 16-15-10421 of the Russian Science Foundation
Twist, left ventricular longitudinal and circumferential strain are early markers of cardiac involvement in Fabry disease
Authors: Menezes Fernandes R , Azevedo O , Cordeiro F , Lourenco M R , Lourenco A
Published: October 2021

Introduction

Fabry disease (FD) is an X-linked progressive and multisystemic disease. Cardiac involvement is common and left ventricular hypertrophy (LVH) is the main cardiac manifestation.

Purpose

To determine the differences in echocardiographic parameters between FD patients without LVH and healthy controls.

Methods

We conducted a prospective study encompassing FD patients followed in a Reference Center of Lysosomal Storage Disorders. All patients performed a complete echocardiographic evaluation, including left ventricular strain analysis by two-dimensional speckle tracking imaging. Demographic, clinical characteristics and echocardiographic parameters were analysed. FD patients without LVH were compared with healthy controls, using Chi-square test for categorical variables and Student's T-test for continuous variables. The significance level was 0,05.

Results

A total of 91 FD patients were included, with a median age of 51 years-old and 62,6% of female predominance. 16,5% of patients were under enzymatic replacement therapy with agalsidase alpha and 7,7% were treated with chaperone therapy (migalastat). 58 patients (64%) did not present LVH. FD patients without LVH were younger (44,2 vs 52,9 years-old, p<0,001), had higher interventricular septum thickness (9,3 vs 8,4 mm, p=0,006) and left ventricular mass index (77,2 vs 68,4 g/m2, p=0,003) than healthy controls. Left ventricular ejection fraction was preserved in both groups (63,3% vs 65,4%; p=0,067). Global longitudinal strain (−19,6% vs −20,9%; p=0,003) and global circumferential strain (−17,9% vs −20,9%; p<0,001) were significantly lower in FD patients without LVH compared to healthy controls. Global radial strain was also lower, although without statistical significance (36,4% vs 41,4%, p=0,058). FD patients without LVH presented a lower base-to-apex circumferential strain gradient (5,7% vs 7,7%; p=0,035), but a higher base-to-apex longitudinal strain gradient (7,5% vs 4,3%; p<0,001), compared to controls. Left ventricular twist was also significantly lower in FD patients without LVH (13,8° vs 21,7°, p<0,001).

Conclusion

Left ventricular strain and twist analysis are useful to identify subclinical myocardial impairment in FD patients without LVH.

Funding Acknowledgement

Type of funding sources: None.
Evaluation of Perugini score and myocardial mass and voltage abnormalities in transthyretine cardiac amyloidosis
Authors: Costa J , Bichon L , Maouche A , Durdon P , Pouy R , Robbins A
Published: October 2021

Background

Transthyretine cardiac amyloidosis (TTR-CA) is an emerging treatable disease in cardiology. Severity of TTR infiltration can be assessed by bone scintigraphy with Perugini score, depending on HPD-Tc99M myocardial intensity uptake. Less is known on how Perugini score interplays with routine cardiac structural parameters, especially cardiac mass and voltage.

Aim

To evaluate correlation between Perugini score and myocardial mass and voltage abnormalities in patients with TTR-CA.

Methods

Patients diagnosed with ATTR-CA and addressed to our center for treatment underwent complete evaluation including electrocardiogram (ECG) and transthoracic echocardiography (TTE). Routine electrical and echographic parameters were obtained such as: Sokolow indice (SV1+RV5) in millivolt (mV), PR delay (ms), QRS width (in ms), left ventricular mass (LVM, in grams) and diastolic interventricular septum (dIVS) thickness (in mm). Patients were classified in three categories according to Perugini score: I (cardiac uptake < chest bones), II (cardiac uptake = chest bones) and III (cardiac uptake > bones). Main end-point were LVM and Voltage/Mass ratio (VMR) variations, depending on Perugini score.

Results

Among the 17 patients included, 14 were male (82.4%) and mean age was 82±8 years old. On ECG, 6 patients (35.3%) had permanent atrial fibrillation (AF). Mean voltage according to Sokolow index, mean PR delay and mean QRS width were respectively 1.5±0.5 mV, 212±54 ms and 113±19 ms. On TTE, mean LVM and mean dIVS width were respectively 333±98 g (188±55 g/m2) and 19±4 mm. Mean voltage/mass ratio (VMR) was 0.48±0.26 uV/g (see table). On bone scintigraphy, 3 patients were scored with Perugini I (17.6%), 4 with Perugini II (23.5%) and 10 with Perugini III (58.8%). According to Pearson test, there was a strong correlation between Perrugini score and LVM (r=+0.56, p=0.03) (graph A), and a strong negative correlation between Perrugini score and VMR (r=−0.70, p=0.003) (graph B). There were a trend for correlation between Perugini score and Voltage according to Sokolow (r=−0.46, p=0.07) and between Perugini score and dIVS width (r=0.49, p=0.07).

Conclusion

In TTR-CA patients, Perugini score appears to strongly correlate with left ventricle mass and voltage. Larger scale studies are needed to confirm these results.

Funding Acknowledgement

Type of funding sources: None. ECG and TEE trends according to PeruginiCardiac mass and voltage with Perugini
Cognitive disorders in takotsubo syndrome: incidence, short and long-term outcome. Results from a prospective multi-center registry
Authors: Mallardi A , Santoro F , Leopizzi A , Vitale E , Iacoviello M , Brunetti N D
Published: October 2021

Background

Takotsubo syndrome (TTS) is an acute and reversible left ventricular dysfunction, whose pathophysiological mechanisms are not completely known. There are evidence suggesting a possible link between neurological disease and TTS. Aim of the study was to evaluate incidence and prognostic value of cognitive neurological disorders among TTS patients.

Methods

379 consecutive patients were enrolled in a prospective multicenter registry. History, clinical features, echocardiographic parameters, in-hospital complications and long-term follow up events of all patients were recorded. Cognitive neurological disorders included Alzheimer disease, old age dementia and cognitive impairment for other causes.

Results

Prevalence of cognitive neurological disorders among TTS patients was 5.5% (num=21). Among this subset of patients 48% (num=10) had Alzheimer syndrome, 24% (num=5) old age dementia and 28% (num=6) cognitive impairment for other causes.

Compared to the control group, these patients were older (81±5 vs 71±12, p=0.01) and predominantly men (24% vs 9%, p=0.01). No differences in term of cardiovascular risk factors and left ventricular ejection fraction at admission and discharge were found among the two groups.

TTS patients with cognitive neurological disorders experienced higher rate of in-hospital complications (62% vs 28% p=0.01), that were mainly driven by higher rate of pulmonary edema (14% vs 9% p=0.01), cardiogenic shock (29% vs 8%, p=0.01), death (24% vs 4% p=0.01), ischemic stroke (10% vs 4% p=0.01) and left ventricular thrombi (10% vs 3%, p=0.01).

At long term follow up patients with cognitive neurological disorders when compared to those without, experienced higher rate of mayor cardiovascular events (48% vs 16%, p=0.01), cardiovascular re-hospitalization (14% vs 10%, p=0.01) and death (43% vs 9%, p=0.01).

Conclusion

TTS patients with cognitive neurological disorders had an increased risk of in and out of hospital mayor cardiac adverse events and mortality at short and long-term follow-up.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Ospedali Riuniti di Foggia-Università di Foggia
Chronic kidney disease in patients with congenital heart disease – a nationwide cohort study
Authors: Gillesen M G , Fedchenko M F , Giang W G K , Dimopoulos K D , Eriksson P E , Dellborg M D , Mandalenakis Z
Published: October 2021

Introduction

Previous studies have shown an association between patients with congenital heart disease (CHD) and chronic kidney disease (CKD). We recently observed an increased prevalence of CKD in children and young adult CHD population, and as nowadays the majority of patients survives into adulthood this might become an increasing complication. However, it is not clear there is an increased risk to develop CKD in CHD patients compared to those without CHD.

Purpose

To investigate the incidence, risk and risk factors for CKD in children and adults with CHD (0–47 years old), compared to age- and sex-matched controls without CHD.

Method

Patients born with CHD between 1970 and 2017 were identified using data from the Swedish health register. Each patient with CHD was matched by birth year and sex to ten controls without CHD from the general population. Follow-up data were collected until 2017.

Results

We identified 71,936 CHD patients (52% male) who were matched to 714,457 controls during mean follow-up of 17.6 years (±12.8). Overall, 379 (0.5%) patients with CHD and 679 (0.1%) controls developed CKD; the risk of CKD was 6,4 times (95% confidence interval (CI): 5.65–7.27, p<0.001) higher in patients with CHD compared to controls. The greatest risk of CKD was in patients with severe non-conotruncal defects (HR 11.31, 95% CI: 7.37–17.36, p<0.001). The incidence of CKD increased exponentially with age but was in patients with and without CHD; however, at age of 47 years the cumulative incidence of CKD was 2.2% and 0.5% in patients with and without CHD respectively. Both absolute and relative risk of CKD was greater in CHD patients in the recent birth cohort (born between 1997–2017) (HR 9.98, 95% CI: 8.05–13.37) (incidence 28.1 per 100,000 person-years) compared to older patients (1970–1996) (HR 5.02 95% CI: 4.28–5.89) (incidence 39.5 per 100,000 person-years). Diabetes mellitus was the only risk factor that associated with the risk of CKD in CHD patients.

Conclusion

In the present nationwide cohort study, we found that patients with CHD have an over 6-fold risk of developing CKD compared to matched controls without CHD. The incidence of CKD increases with age, but also younger CHD patients are at risk, prompting action to establish regular follow-up of renal function in all patients with CHD, and identify individuals at risk as early as possible. Further mapping of risk factors and effects of kidney disease on the CHD population is also required.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): The Swedish state and the Swedish Research Council
Infective endocarditis in adult patients with congenital heart disease: results from the ESC EORP EURO-ENDO registry
Authors: Van Melle J , Roos-Hesselink J , Bansal M , Kamp O , Meshaal M , Pudich J , Reskovic Luksic V , Rodriguez-Alvarez R , Sadeghpour A , Separovic Hanzevacki J , Sow R , Timoteo A T , Laroche C , Lancellotti P , Habib G ,   EURO-ENDO Investigators group
Published: October 2021

Background

Congenital Heart Disease (CHD) predisposes to Infective Endocarditis (IE)

Purpose

To characterize and to determine the prognosis of IE in this specific population.

Methods

The ESC EORP EURO-ENDO study is a prospective international study in patients (n=3111) diagnosed with IE. In this pre-specified ancillary analysis, we aimed to describe adult patients with CHD (n=365, 11·7%) and compare them with patients without CHD (non-CHD, n=2746) in terms of baseline characteristics and 1-year outcome.

Results

CHD patients (73% men, age 44·8±16·6 years) were younger and had less comorbidities. Of the CHD patients, 14% had a dental procedure in the 6 months before hospitalization versus 7% in non-CHD patients (p<0·001) and more often positive blood cultures for Streptococcus viridans (16·4% vs 8·8%, p<0·001). As in non-CHD patients, IE affected most often the left-sided valves. For CHD patients, in-hospital mortality was 9·0% vs 18·1% in non-CHD patients (p<0·001), and also 1-year outcome was more favourable (log-rank for all-cause mortality p<0·0001), even after adjustment for age (Hazard Ratio (HR) 0·61; 95% CI 0·45–0·81). Within the CHD population, multivariable Cox regression revealed the following predictors for mortality: fistula (HR 6·97), cerebral embolus (HR 4·64), renal insufficiency (HR 3·44), Staphylococcus aureus as causative agent (HR 2·06) and failure to undertake surgery when indicated (HR 5·93).

Conclusion

CHD patients with IE have better outcome in terms of all-cause mortality. The observed high incidence of dental procedures prior to IE fuels the discussion about the need for antibiotic prophylaxis.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Since the start of EORP, the following companies have supported the program: Abbott Vascular Int. (2011–2021), Amgen Cardiovascular (2009–2018), AstraZeneca (2014–2021), Bayer AG (2009–2018), Boehringer Ingelheim (2009–2019), Boston Scientific (2009–2012), The Bristol Myers Squibb and Pfizer Alliance (2011–2019), Daiichi Sankyo Europe GmbH (2011–2020), The Alliance Daiichi Sankyo Europe GmbH and Eli Lilly and Company (2014–2017), Edwards (2016–2019), Gedeon Richter Plc. (2014–2016), Menarini Int. Op. (2009–2012), MSD-Merck & Co. (2011–2014), Novartis Pharma AG (2014–2020), ResMed (2014–2016), Sanofi (2009–2011), Servier (2009–2021), Vifor (2019–2022). Survival CHD vs non-CHD patients
A comparison of ECG-based home monitoring devices in adults with congenital heart disease
Authors: Bokma J P , Pengel L K D , Robbers-Visser D , Groenink M , Boekholdt S M , Bouma B J
Published: October 2021

Background

Various devices are available for electrocardiogram (ECG) based home monitoring and could facilitate early detection of arrhythmias in adult congenital heart disease (ACHD). However, the diagnostic accuracy of these devices in ACHD is unknown.

Purpose

We aimed to determine the accuracy of different ECG-based devices compared to the standard 12-lead ECG in ACHD.

Methods

We performed a single-center, prospective, cross-sectional study in consecutive ACHD patients. We determined diagnostic accuracy of the Withings Scanwatch (lead I), Eko DUO (precordial ECG) and Kardia 6L (six leads) compared to the 12-lead ECG on several parameters: 1) automatic atrial fibrillation (AF) detection, 2) QRS-morphology assessment (simplified into normal (<120ms), right bundle branch block (>120ms) or other wide complexes (>120ms)), and 3) conduction times (PR, QRS, QTc time). All 12-lead and device ECGs were evaluated by a single observer.

Results

A total of 176 patients (54% male, age 40±16.6 years, 24% severe ACHD, 84% previous correction, six patients with AF) enrolled in the study. The Withings algorithm classified only 5% of ECGs as inconclusive compared to 31% of Kardia 6L (p<0.001). Both devices had comparable sensitivity and specificity (Withings: 100% and 100% vs. Kardia 6L: 100% and 97%) in ECGs that were classified by the algorithm. On Kardia 6L, QRS morphology was correctly classified more frequently (90%) compared to EKO duo (84%) (p=0.03) and identified the P-wave more frequently (85%) (p<0.001 compared to both). Evaluation of all ECG-based devices underestimated QTc and QRS duration compared to the 12L ECG (p<0.01). Withings (49%) more frequently over- or underestimated QTc-interval by more than 40msec compared to Eko DUO (30%) and Kardia 6L (26%) (p<0.001 for both). Overall, ECG quality of Withings Scanwatch was rated worse compared to Kardia 6L and EKO duo (p<0.001 for both).

Conclusions

This is the first study to examine diagnostic accuracy of different ECG-based devices in ACHD. Overall, Withings Scanwatch may be the most practical choice for continuous AF screening while Kardia 6L could be preferred to accurately capture symptomatic palpitations. These findings can inform both patients and caregivers for optimal choice of home monitoring.

Funding Acknowledgement

Type of funding sources: None.
Hemodynamic effects of balloon pulmonary angioplasty for the treatment of total and subtotal pulmonary artery occlusions in inoperable chronic thromboembolic pulmonary hypertension
Authors: Stepniewski J , Magon W , Przybylski R , Kopec G
Published: October 2021

Background

Balloon pulmonary angioplasty (BPA) has become a therapeutic option for inoperable chronic thromboembolic pulmonary hypertension (CTEH). Despite significant improvement in the technique, treatment of subtotal (STO) and total (TO) pulmonary artery occlusions with BPA may pose risk, but the efficacy is unknown.

Aim

We aimed to study to assess safety and efficacy of BPA in STO/TO.

Methods

We included consecutive patients with inoperable CTEPH, who underwent BPA treatment. To evaluate the efficacy and safety we grouped all BPA sessions into those in which recanalization of at least one STO or TO was performed and into those without. The primary efficacy outcome was improvement in pulmonary vascular resistance (PVR) in BPA sessions with STO/TO recanalization as compared to those without.

Results

We analyzed 169 BPA sessions in 50 CTEPH patients. Out of a total number of 832 lesions subjected for BPA, 168 were classified as STOs or TOs [129 (15,5%) and 39 (4,7%) respectively]. Three (2,3%) STOs and 8 (20,5%) TOs were not recanalized despite repeated attempts. There were 90 BPA sessions with at least one STO/TO recanalization. Racanalization of at least one STO/TO was associated with a trend towards PVR improvement as compared to non-STO/TO BPAs (−69±162 vs −38±135 dyn s cm–5, p=0,19). Recanalization of STO/TO at the level of segmental pulmonary artery as compared to subsegmental-only STO/TO recanalizations or no-STO/TO recanalization was associated with significant PVR improvement (−126±192 vs −38±135 dyn s cm–5, p=0.007). The rate of complications was similar in STO/TO and non-STO/TO BPA sessions (14.4% vs 12.6%, p=0.56).

Conclusions

The use of BPA for the recanalization of subtotal and total PA occlusions is safe and effective. Recanalization of segmental STO/TOs leads to significant improvement in PVR.

Funding Acknowledgement

Type of funding sources: None.
Efficacy and safety of early switch to oral anticoagulation in acute intermediate-risk pulmonary embolism
Authors: Klok F A , Toenges G , Barco S , Konstantinides S V ,   PEITHO-2 investigators
Published: October 2021

Background

Guidelines recommend risk-adjusted management of pulmonary embolism (PE). We investigated whether treatment of acute intermediate-risk PE with parenteral anticoagulation for a short period of 72 hours, followed by switch to a direct oral anticoagulant (dabigatran), is effective and safe.

Methods

We conducted a prospective multicentre single-arm management trial in patients with intermediate-risk PE (EudraCT Identifier 2015–001830–12). Patients received parenteral heparin, switched to dabigatran 72 hours after diagnosis following standardised clinical assessment. The study was terminated early following sample size adaptation after the predefined interim analysis.

Findings

From January 2016 through July 2019, 402 patients were enrolled in 9 European countries. Adherence to protocol was 92.0% (Table 1). The primary outcome, recurrent symptomatic venous thromboembolism or PE-related death within 6 months (Table 2), occurred in 7 patients (1.7%; upper bound of right-sided 95% CI 3.2%; p=0.ehab724.192322 for rejecting H0), with all events in the intermediate-high-risk group (2.5%; upper bound of right-sided 95% CI 4.6%). Median duration of hospitalisation for the index event was 6 days, despite the fact that >70% of the patients had intermediate-high-risk PE. The six-month incidence of major bleeding was 2.7%; the only fatal haemorrhage occurred before switch to dabigatran.

Interpretation

A strategy of early switch from heparin to dabigatran following standardised clinical assessment was effective and safe in intermediate-risk PE. Our results can help to fine-tune guideline recommendations for initial treatment of PE, optimising the use of resources and avoiding prolonged hospitalisation.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Federal Ministry of Education and Research; and Boehringer Ingelheim Table 1. Time between diagnosis of pulmonary embolism and switch to dabigatran (N = 402 patients)Table 2. Efficacy and safety outcomes
The Birmingham Black Country Venous Thromboembolism (BBC-VTE) registry of outcomes of venous thromboembolism patients admitted to hospital
Authors: Sanders A , El-Bouri W K , Lip G Y H ,   Birmingham Black Country Venous Thromboembolism Investigators
Published: October 2021

Background

Venous thromboembolism (VTE) is a condition which causes significant morbidity and mortality in hospitalised patients as well as in the community. These are related to adverse outcomes associated with the first incidence of VTE, such as recurrence, major haemorrhage and mortality. These outcomes are difficult to measure and compare among the different regions of the world not least because of varying prevalence of risk factors, paucity of comparable studies and a differing approach to treatment of VTE (1–3).

Purpose

Our VTE registry aims to estimate the above mentioned outcomes as applicable to a developed world population with a multi-ethnic background. Furthermore, our registry has provided a data set to develop and validate a machine learning algorithm in order to predict outcomes in patients admitted to hospital with VTE. This will have profound implications for clinicians who will be able to make evidence-based decisions about which patients are low risk and so can be discharged early as well as those who are high risk and may need more intensive follow up.

Methods

BBC-VTE registry is a retrospective, multi-centre, observational registry. We identified all patients (N=1554) who were admitted with a final radiologically confirmed diagnosis of pulmonary embolism and/or lower limb deep vein thrombosis at three regional hospitals in the UK during the years 2012–2014. Each patient's electronic record was accessed by clinicians to confirm radiological diagnosis of VTE and also collect data on demographics, physical examination findings and laboratory analysis on admission, past medical history, and treatment plan. Outcomes were also recorded including recurrence of VTE, subsequent major bleeding and all-cause mortality.

A simple multivariate analysis (logistic regression) was used to determine risk factors associated with all-cause mortality. Odds ratios (OR) and 95% CI are reported.

Results

The main factors determining higher all-cause mortality were age, a history of diabetes, admission laboratory analysis (c-reactive protein and neutrophil count), and previous malignancy (OR >1) (see Fig. 1). Conversely, hypercholesterolaemia, discharge oral anticoagulation, immobilization, and post-PE syndrome were all significantly correlated with a reduced risk of mortality (OR <1).

Conclusions

BBC-VTE provides unique data on VTE mortality risks in a multi-ethnic cohort. The strengths of our registry are that we are only including radiologically verified VTE patients unlike many of the epidemiological studies to date which rely on clinical coding. We have also shown that it is possible to risk-stratify patients admitted with VTE using simple clinical variables which has implications for their discharge decisions.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Impact of left heart disease risk factors on risk stratification and treatment response in pulmonary arterial hypertension
Authors: Kearney K , Anderson J , Cordina R , Lavender M , Celermajer D , Collins N , Dwyer N , Keating D , Williams T , Whitford H , Whyte K , Weintraub R , Keogh A , Kotlyar E , Lau E M T
Published: October 2021

Background

Contemporary registries have documented a change in the epidemiology of PAH patients displaying increasing co-morbidities associated with left heart disease (LHD). These patients are often excluded from randomized clinical trials. It is unclear whether the presence of LHD comorbidities may adversely impact the accuracy of risk stratification and response to PAH therapy.

Method

Data was extracted from the Pulmonary Hypertension Society of Australia and New Zealand registry for incident patients with a diagnosis with idiopathic/heritable/toxin-induced (I/H/D)-PAH and connective tissue disease (CTD) associated PAH from 2011 - 2020. Patients without available medication and follow up data were excluded. We used the AMBITION trial exclusion criteria to define the subpopulation with LHD risk factors and haemodynamic phenotype (PAH-rLHD).

Results

489 patients (I/H/D-PAH=251, CTD-PAH=238) were included in our analysis, with 103 (21.0%) fulfilling the definition of PAH-rLHD (34 had ≥3 risk factors for left heart disease (rLHD-hypertension, diabetes, obesity or ischaemic heart disease) and 76 had borderline haemodynamics (mean capillary wedge pressure 13–15 with pulmonary vascular resistance <500 dynes sec/cm5) including 7 who met both criteria). Compared to classical PAH, patients with PAH-rLHD were older at diagnosis (66±13 vs 58±19, p<0.001), had lower pulmonary vascular resistance (PVR: 393±266 vs 708±391, p=0.031) but worse exercise capacity (6MWD: 286±130m vs 327±136m, p=0.005). PAH-rLHD were more likely to be started on initial monotherapy, compared with “classical” PAH (73% vs 56%, p=0.002). In the monotherapy groups, endothelin receptor antagonists (ERA) were used in 73% PAH-rLHD, compared with 66% in classical PAH group. Both groups exhibited similar response to both mono- and combination therapy with commensurate improvements in WHO functional class (mean change 0.3±0.6 vs 0.3±0.8, p=0.443) and 6-minute walk distance (mean change 44±82 vs 48±101, p=0.723). There was no difference in survival between classical PAH and PAH-rLHD (log rank, p=0.29). The REVEAL 2.0 risk score effectively discriminated risk in both populations at baseline and first follow up (classical PAH: baseline C statistic 0.750, follow up 0.774 and PAH-rLHD: baseline C statistic 0.756, follow up 0.791).

Conclusion

Despite lower PVR at diagnosis, PAH-rLHD patients and “classical” PAH demonstrate similar response to first-line therapy with similar long term survival. The REVEAL 2.0 risk score can be effectively applied to the subpopulation of PAH-rLHD in real life clinical practice.

Funding Acknowledgement

Type of funding sources: None.
Atrioventricular plane displacement and regional contribution to stroke volume to predict outcome in pulmonary arterial hypertension
Authors: Lindholm A , Kjellstrom B , Seemann F , Carlsson M , Hesselstrand R , Radegran G , Arheden H , Ostenfeld E ,   Lund Cardiac MR Group
Published: October 2021

Background

Patients with pulmonary arterial hypertension (PAH) exhibit high mortality, partially related to right heart failure. Right ventricular (RV) volumes and ejection fraction (EF) can be measured accurately with cardiac magnetic resonance (CMR), but EF is a crude measure of cardiac function. Additional methods for risk assessment and prognosis are of value. Stroke volume (SV) is generated by longitudinal, lateral and septal myocardial contraction. Longitudinal contribution to SV (SVlong%) generated from the atrioventricular displacement (AVPD) is the major contributor to SV in both the left ventricle (LV) and RV. AVPD in both sides and LVSVlong% are lower in patients with PAH compared to controls. However, it is unknown if altered AVPD or regional contributions to SV are prognostic in patients with PAH. The aim of this study was therefore to evaluate if AVPD, longitudinal, lateral or septal contribution to LVSV and RVSV are associated with death or lung transplantation in patients with PAH.

Purpose

To evaluate if biventricular AVPD, and regional contributions to SV are associated with outcome in patients with PAH.

Methods

Seventy-one patients with PAH and 20 sex and age-matched healthy controls underwent CMR. Endocardial and epicardial borders and RV insertion points were defined in end diastole and end systole in cine short-axis stacks to compute biventricular volumes, SVlat% and SVsept%. Eight atrioventricular points were defined in end diastole and end systole in 2-, 3- and 4-chamber cine long-axis views, for computation of AVPD and SVlong%. Cut-off values for survival analysis were defined as above or below mean ± 2 standard deviations from the healthy controls. Outcome was defined as death or lung-transplantation.

Results

Median follow-up time was 3.6 [IQR 3.7] years. AVPD, SVlong%, SVlat% in both ventricles and SVsept% were altered in PAH compared to controls. Transplantation-free survival was lower with values below cut-off for LV-AVPD (hazard ratio (HR)=2.1, 95% CI: 1.2–3.9, p=0.02) and RV-AVPD (HR=9.8, 95% CI: 4.6–21.1, p=0.005) (fig 1). In cox regression analysis, decreased LV-AVPD and RV-AVPD inferred lower transplantation-free survival (LV: HR=1.16 per mm decrease, p=0.007; RV: HR=1.11 per mm decrease, p=0.01) (table 1). LVEF, RVEF, LV-SVlong%, RV-SVlong%, LV-SVlat%, RV-SVlat% or SVsept% did not affect outcome (table 1).

Conclusions

Decreased left and right AVDP were associated with decreased transplantation-free survival in patients with PAH. There were no associations between ejection fraction, longitudinal, lateral or septal contribution to stroke volume.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Skåne University Hospital, Region of Skåne Southern Healthcare Region of Sweden
Involvement of FAK in aortic dissection: potential role in aortic interstitial cells
Authors: Majima R , Aoki H , Shibata R , Nakao E , Hashimoto Y , Hayashi M , Ohno-Urabe S , Furushyo A , Nishida N , Hirakata S , Fukumoto Y
Published: October 2021

Background

Aortic dissection (AD) is a fatal disease where the intimomedial layer of the aorta suddenly fail. Although it is widely accepted that hemodynamic stress on the aortic wall triggers its destruction that is further promoted by inflammatory response as exemplified by the infiltration of neutrophils and macrophages, molecular mechanism is unknown for the link of aortic wall stress, inflammation and tissue destruction. In general, mechanical stress to the tissue is converted to the cellular response through the cell adhesion molecules and the activation of focal adhesion kinase (Fak). Although it has been reported that Fak is involved in pathogenesis of aortic aneurysm by promoting migration and activation of macrophages, its role in AD is unknown. We hypothesized that Fak may be involved in AD pathogenesis.

Purpose

We investigated the involvement of Fak in AD pathogenesis, focusing on its role in inflammatory cells.

Methods and results

We created a mouse model of AD by continuous infusion of beta-aminopropionitrile, a collagen crosslink inhibitor, and angiotensin II (BAPN + Ang II). Immunostaining for activated Fak revealed that Fak was not activated in normal aorta, but was activated in the infiltrating inflammatory cells and in interstitial cells of the aortic wall after AD development. We examined the role of Fak by oral administration of PND-1186, a specific Fak inhibitor, in mouse AD model. Vehicle-treated group showed 63.6% mortality, whereas PND-1186-treated group showed 20% mortality (P<0.01, n=20 for each group) in 14 days of the observational period. The aortic arch lesion, the most critical part in AD, was improved from 1.96±0.41 mm in vehicle group to 0.66±0.29 mm in PND group (P<0.05). We next examined the cell type-specific role of Fak in AD by creating macrophage and granulocyte-specific deletion of Fak driven by LysM-Cre and floxed Fak system. Unexpectedly, the genetic deletion of Fak in macrophages and granulocytes had no impact on the mortality nor the severity of AD.

Conclusions

These findings proved that Fak plays a critical role in AD progression and death. Because Fak is dispensable for macrophages and granulocytes, other cell types, possibly aortic wall interstitial cells, may be regulated by Fak in AD pathogenesis. Deciphering the role of Fak would provide the fundamental understanding of AD pathogenesis.

Funding Acknowledgement

Type of funding sources: None.