Mariëlle Kloosterman

Refining success of cardiac resynchronization therapy using a simple score predicting the amount of reverse ventricular remodelling : results from the Markers and Response to CRT (MARC) study

Aims Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in systolic heart failure patients with ventricular conduction delay. Variability of individual response to CRT warrants improved patient selection. The Markers and Response to CRT (MARC) study was designed to investigate markers related to response to CRT. Methods and results We prospectively studied the ability of 11 clinical, 11 electrocardiographic, 4 echocardiographic, and 16 blood biomarkers to predict CRT response in 240 patients. Response was measured by the reduction of indexed left ventricular end-systolic volume (LVESVi) at 6 months follow-up. Biomarkers were related to LVESVi change using log-linear regression on continuous scale. Covariates that were significant univariately were included in a multivariable model. The final model was utilized to compose a response score. Age was 67 ± 10 years, 63% were male, 46% had ischaemic aetiology, LV ejection fraction was 26 ± 8%, LVESVi was 75 ± 31 mL/m2, and QRS was 178 ± 23 ms. At 6 months LVESVi was reduced to 58 ± 31 mL/m2 (relative reduction of 22 ± 24%), 130 patients (61%) showed ≥ 15% LVESVi reduction. In univariate analysis 17 parameters were significantly associated with LVESVi change. In the final model age, QRSAREA (using vectorcardiography) and two echocardiographic markers (interventricular mechanical delay and apical rocking) remained significantly associated with the amount of reverse ventricular remodelling. This CAVIAR (CRT-Age-Vectorcardiographic QRSAREA -Interventricular Mechanical delay-Apical Rocking) response score also predicted clinical outcome assessed by heart failure hospitalizations and all-cause mortality. Conclusions The CAVIAR response score predicts the amount of reverse remodelling after CRT and may be used to improve patient selection. Clinical Trials: NCT01519908.

Atrial reverse remodelling is associated with outcome of cardiac resynchronization therapy

AIMS To study the prognostic effect of atrial reverse remodelling on outcome of cardiac resynchronization therapy (CRT). METHODS AND RESULTS Patients receiving a CRT device in the University Medical Centre Groningen were included. Atrial reverse remodelling was defined as a ≥10% reduction in left atrial volume index at 6-month follow-up. Success of CRT was defined as ventricular reverse remodelling with a reduction in left ventricular end-systolic volume of ≥15% at 6-month follow-up. Primary endpoint was all-cause mortality or heart failure hospitalizations. A total of 365 patients (mean age 65.1 ± 11.0 years, 73% men) were included; among them, 221 (61%) were in sinus rhythm and had no prior atrial fibrillation (AF), and 144 patients (39%) had a history of AF. During a mean follow up of 2.0 ± 1.0 years, 49 patients died. Cox regression analysis revealed that patients with no atrial and no ventricular reverse remodelling had the worst outcome (hazard ratio 3.1, 95% confidence interval 1.4-7.1, P = 0.006). Outcome in patients with only atrial reverse remodelling was comparable with outcome in patients with both atrial and ventricular reverse remodelling (hazard ratio 2.0, 95% confidence interval 0.7-5.6, P = 0.21). CONCLUSION Patients without atrial and ventricular reverse remodelling have the worst outcome. Patients with only atrial reverse remodelling have improved left ventricular diastolic filling during follow-up and demonstrate a comparable outcome with patients with both atrial and ventricular reverse remodelling. Assessment of atrial reverse remodelling may provide additional prognostic information in determining CRT outcome.

The importance of myocardial contractile reserve in predicting response to cardiac resynchronization therapy

To perform a meta‐analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization therapy (CRT) in patients with heart failure.

Spontaneous resolution of left bundle branch block and biventricular stimulation lead to reverse remodeling in dyssynchronopathy

Left bundle branch block (LBBB) is considered a marker of underlying structural cardiac disease. To determine whether LBBB is cause or consequence of deterioration of left ventricular (LV) function is difficult as both are often diagnosed concomitantly. We discuss a patient where reversal of LBBB and subsequent normalization of LV function was observed after 2 different therapies, first after start of heart failure medication, and years later after implantation of a cardiac resynchronization device. This indicates that LBBB per se may result in the development of non-ischemic cardiomyopathy and that LBBB resolution can lead to reverse remodeling in dyssynchronopathy.

Atrial Fibrillation During Cardiac Resynchronization Therapy

The landmark trials on cardiac resynchronization therapy (CRT) have focused on patients with sinus rhythm at inclusion. Little data are available on the efficacy of CRT in patients with atrial fibrillation (AF), while AF has a high prevalence (20-40%) among patients receiving CRT. This review focuses on the detrimental effect of AF on CRT response and discusses management of patients with AF during CRT. Uncertainty remains as to which thresholds of AF burden can lead to a reduced response to CRT and every effort should be made in trying to assess and guarantee successful biventricular pacing in patients with AF.

The left atrium: An overlooked prognostic tool

The increasing incidence and prevalence of chronic kidney disease (CKD) is associated with a parallel rise in atrial fibrillation (AF). The main reason for this epidemiological coupling is an increasing elderly population and shared risk factors, such as diabetes mellitus, hypertension and heart failure. However, more and more data are becoming available to suggest that both diseases likely share underlying pathophysiological mechanisms (Figure 1). Cardiovascular events, rather than renal failure itself, are the most common cause of mortality and morbidity in patients with CKD. The presence of both CKD and AF exacerbates vascular-related adverse events (including stroke, systemic thromboembolism, heart failure and myocardial infarction). Unsurprisingly, structural and functional cardiac abnormalities are already present in CKD patients without overt cardiac disease. Diastolic dysfunction has a prevalence of 29% in patients with non-dialysis CKD. This may be one of the triggers of left atrial (LA) enlargement, which is an established predictive marker of AF and cardiovascular events. In this issue of the European Journal of Preventive Cardiology, Nakanishi et al. used real time 3-D echocardiography to study the association between CKD and LA volume and function in 358 patients from a community-based cohort study without overt cardiac disease. CKD (estimated glomerular filtration rate (eGFR)) <60ml/min/1.73 m) was present in 69 patients (19%). These were patients early in the disease process: kidney function was relatively preserved and LA volumes were within the normal range. However, patients with CKD (mean eGFR 50 9ml/min/ 1.73m) had a higher prevalence of diastolic dysfunction and reduced LA emptying fraction (42.7 11.4 versus 47.8 11.5%). Multivariate regression analysis showed that eGFR was associated with LA emptying fraction, independent of age, left ventricular mass index and diastolic dysfunction, but not with LA volume. Whereas LA maximum volume remained unchanged between the groups, early CKD was independently associated with impaired LA function. LA enlargement may eventually develop as renal dysfunction progresses. The authors are to be congratulated on this elegant and timely study. However, the results must be interpreted in light of limitations that are inherent to its design and small study population. Furthermore, patients with CKD were older, more often had hypertension, and received different pharmacological treatment, possibly influencing LA parameters. Additionally, information on aetiology and duration of CKD, and outcome parameters such as AF occurrence, are missing. Nevertheless, the observations are in line with data from Kadappu et al. who showed that patients with CKD have altered LA function and LA enlargement compared with risk factor-matched control subjects and healthy subjects. Indeed, AF often occurs in the setting of CKD. In the Atherosclerosis Risk in Communities study, newonset AF was increasingly prevalent as GFR declined. Patients with GFR of 60–89, 30–59 and 15–29ml/min/ 1.73m had, compared to patients with GFR 90ml/ min/1.73m, hazard ratios (HRs) of 1.3, 1.6 and 3.2, respectively, for developing AF during a follow-up of 10 years. In 8265 individuals included in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, microalbuminuria, as a measure of renal vascular dysfunction, was related to incidence of new-onset AF during a follow-up of almost 10 years, independent of cardiovascular risk factors. Likewise, patients with AF have a higher incidence of CKD. In a UK cohort of 4.3 million adults, linked

Atrial Fibrillation During Cardiac Resynchronization Therapy.

The landmark trials on cardiac resynchronization therapy (CRT) have focused on patients with sinus rhythm at inclusion. Little data are available on the efficacy of CRT in patients with atrial fibrillation (AF), while AF has a high prevalence (20-40%) among patients receiving CRT. This review focuses on the detrimental effect of AF on CRT response and discusses management of patients with AF during CRT. Uncertainty remains as to which thresholds of AF burden can lead to a reduced response to CRT and every effort should be made in trying to assess and guarantee successful biventricular pacing in patients with AF.