Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death

Aims This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation.Methods and results We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality.Conclusion Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed.Cardiolog

Cardiopulmonary aspects of hereditary haemorrhagic telangiectasia

This thesis addresses several clinical aspects of pulmonary arteriovenous malformations (PAVMs) in patients with hereditary haemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber disease. HHT is characterized by arteriovenous malformations (AVMs) in multiple organs and inherited as an autosomal dominant trait. PAVMs result in a right-to-left shunt which bypasses the pulmonary capillary filter, and are responsible for a high prevalence of brain abscess and ischemic stroke in HHT patients. Therefore, all HHT patients are routinely screened for PAVMs. Results In the first part we compared TTCE as a screening technique for PAVM with chest computed tomography (CT) as the gold standard, in a prospective study of almost 300 patients. The sensitivity of TTCE was 97% and negative predictive value 99%. However, no treatable PAVMs were missed. TTCE was also positive in 59% of patients without a PAVM on chest CT. Therefore, it appears that TTCE detects even small intrapulmonary shunts below the detection limit of CT. In a second study, the use of semi-quantitative grading (minimal, moderate, and large) of pulmonary shunt size was investigated. We showed that in patients with small shunts, no treatable PAVMs were found. This implies that a chest CT can be withheld in this group of patients. In the second part we show that a pulmonary shunt on TTCE is more prevalent and larger in HHT1 relatives (positive TTCE in 85%, of which 54% large shunts), as compared with HHT2 related mutation carriers (positive TTCE in 35%, of which 59% small shunts). Shunt grading is particularly helpful in HHT2 patients, as most patients in this group have small shunts. TTCE appeared to be also positive in 6.3% of persons without HHT. The clinical diagnosis of HHT is based on the presence of at least three of four criteria, of which one is the presence of visceral AVMs. We studied the use of TTCE to assess this criterium. The use of TTCE slightly improved clinical diagnosis in patients with genetically confirmed HHT, but also raised false positive clinical diagnosis from 0 to 6.5% in persons without HHT. In the third part we show that a PAVM on chest CT is independently associated with MA (OR 3.0, 95% CI 1.00–9.20; p=0.05). Using echocardiographic shunt grading, a large shunt increased the risk for MA more than seven-fold after multivariate analysis (OR 7.61; 95% 3.11-18.61; p<0.001). Small and moderate shunts were not associated with MA. Conclusion TTCE can be used as a first-line screening test for PAVM, only followed by chest CT to detect treatable PAVMs when positive for a pulmonary shunt. A graded approach of intrapulmonary shunting should be employed to identify patients with small pulmonary shunts in whom unnecessary additional testing can be prevented. A pulmonary shunt on TTCE should not automatically be regarded as a clinical criterium for HHT because it raises false-positive diagnosis. This relates to the presence of a small intrapulmonary shunts in a part of the general population. A large intrapulmonary shunt, but not shunts of lesser degree, is a strong independent predictor for MA+

Heart failure treatment in patients with and without obesity with an ejection fraction below 50%

BackgroundThe aim of this study was to assess heart failure (HF) treatment in patients with and without obesity in a large contemporary real-world Western European cohort. MethodsPatients with a left ventricular ejection fraction (LVEF) = 30 kg/m(2)) was performed. ResultsSeven thousand six hundred seventy-one patients were included, 1284 (16.7%) had a BMI >= 30 kg/m(2), and 618 (8.1%) had a BMI >= 35 kg/m(2). Median BMI was 26.4 kg/m(2). Patients with obesity were younger and had a higher rate of comorbidities such as diabetes mellitus, hypertension and obstructive sleep apnoea (OSAS). Prescription rates of guideline-directed medical therapy (GDMT) increased significantly with BMI. The differences were most pronounced for mineralocorticoid receptor antagonists (MRAs) and diuretics. Patients with obesity more often received the guideline-recommended target dose. In multivariable logistic regression, obesity was significantly associated with a higher likelihood of receiving >= 100% of the guideline-recommended target dose of beta-blockers (OR 1.34, 95% CI 1.10-1.62), renin-angiotensin system (RAS)-inhibitors (OR 1.34, 95% CI 1.15-1.57) and MRAs (OR 1.40, 95% CI 1.04-1.87). ConclusionsGuideline-recommended HF drugs are more frequently prescribed and at a higher dose in patients with obesity as compared to HF patients without obesity

Age differences in contemporary treatment of patients with chronic heart failure and reduced ejection fraction

Background: Elderly patients are underrepresented in clinical trials but comprise the majority of heart failure patients. Data on age-specific use of heart failure therapy are limited. The European Society of Cardiology heart failure guidelines provide no age-specific treatment recommendations. We investigated practice-based heart failure management in a large registry at heart failure outpatient clinics. Design and methods: We studied 8351 heart failure with reduced ejection fraction patients at 34 Dutch outpatient clinics between 2013 and 2016. The mean age was 72.3 ± 11.8 years and we divided age into three categories: less than 60 years (13.9%); 60–74 years (36.0%); and 75 years and over (50.2%). Results: Elderly heart failure with reduced ejection fraction patients (≥75 years) received significantly fewer beta-blockers (77.8% vs. 84.2%), renin–angiotensin system inhibitors (75.2% vs. 89.7%), mineralocorticoid receptor antagonists (50.6% vs. 59.6%) and ivabradine (2.9% vs. 9.3%), but significantly more diuretics (88.1% vs. 72.6%) compared to patients aged less than 60 years (Pfor all trends < 0.01). Moreover, the prescribed target dosages were significantly lower in elderly patients. Also, implantable cardioverter defibrillator (18.9% vs. 44.1%) and cardiac resynchronisation therapy device (14.6% vs. 16.7%) implantation rates were significantly lower in elderly patients. A similar trend in drug prescription was observed in patients with heart failure with mid-range ejection fraction as in heart failure with reduced ejection fraction. Conclusion: With increasing age, heart failure with reduced ejection fraction patients less often received guideline-recommended medication prescriptions and also in a lower dosage. In addition, a lower percentage of implantable cardioverter defibrillator and cardiac resynchronisation therapy device implantation in elderly patients was observed

Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death

AIMS: This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation. METHODS AND RESULTS: We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality. CONCLUSION: Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed

Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death

Aims This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation.Methods and results We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality.Conclusion Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed