Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart

Right heart function is the main determinant of prognosis in pulmonary arterial hypertension (PAH). At present, no treatments are currently available that directly target the right ventricle, as we will demonstrate in this article. Meta-analysis of clinical trials in PAH revealed that current PAH medication seems to have limited cardiac-specific effects when analysed by the pump-function graph. Driven by the hypothesis that "left" and right heart failure might share important underlying pathophysiological mechanisms, we evaluated the clinical potential of left heart failure (LHF) therapies for PAH, based on currently available literature. As in LHF, the sympathetic nervous system and the renin–angiotension–aldosterone system are highly activated in PAH. From LHF we know that intervening in this process, e.g. by angiotensin-converting enzyme inhibition or β-blockade, is beneficial in the long run. Therefore, these medications could be also beneficial in PAH. Furthermore, the incidence of sudden cardiac death in PAH could be reduced by implantable cardioverter-defibrillators. Finally, pilot studies have demonstrated that interventricular dyssynchrony, present at end-stage PAH, responded favourably to cardiac resynchronisation therapy as well. In conclusion, therapies for LHF might be relevant for PAH. However, before they can be implemented in PAH management, safety and efficacy should be evaluated first in well-designed clinical trials

Altered left atrial 4D flow characteristics in patients with paroxysmal atrial fibrillation in the absence of apparent remodeling

The pathophysiology behind thrombus formation in paroxysmal atrial fibrillation (AF) patients is very complex. This can be due to left atrial (LA) flow changes, remodeling, or both. We investigated differences for cardiovascular magnetic resonance (CMR)-derived LA 4D flow and remodeling characteristics between paroxysmal AF patients and patients without cardiac disease. In this proof-of-concept study, the 4D flow data were acquired in 10 patients with paroxysmal AF (age=61 +/- 8 years) and 5 age/gender matched controls (age=56 +/- 1 years) during sinus rhythm. The following LA and LA appendage flow parameters were obtained: flow velocity (mean, peak), stasis defined as the relative volume with velocities<10 cm/s, and kinetic energy (KE). Furthermore, LA global strain values were derived from b-SSFP cine images using dedicated CMR feature-tracking software. Even in sinus rhythm, LA mean and peak flow velocities over the entire cardiac cycle were significantly lower in paroxysmal AF patients compared to controls [(13.12.4 cm/s vs. 16.7 +/- 2.1 cm/s, p=0.01) and (19.3 +/- 4.7 cm/s vs. 26.8 +/- 5.5 cm/s, p=0.02), respectively]. Moreover, paroxysmal AF patients expressed more stasis of blood than controls both in the LA (43.2 +/- 10.8% vs. 27.8 +/- 7.9%, p=0.01) and in the LA appendage (73.3 +/- 5.7% vs. 52.8 +/- 16.2%, p=0.04). With respect to energetics, paroxysmal AF patients demonstrated lower mean and peak KE values (indexed to maximum LA volume) than controls. No significant differences were observed for LA volume, function, and strain parameters between the groups. Global LA flow dynamics in paroxysmal AF patients appear to be impaired including mean/peak flow velocity, stasis fraction, and KE, partly independent of LA remodeling. This pathophysiological flow pattern may be of clinical value to explain the increased incidence of thromboembolic events in paroxysmal AF patients, in the absence of actual AF or LA remodeling.Cardiovascular Aspects of Radiolog

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

Magnetic resonance imaging in patients with cardiac implantable electronic devices

In recent years the prevalence of implantation of acardiac implantable electronic device (CIED) has increased due to expanding implantation indications and prolonged life expectancy. Diagnostic strategies increasingly employ magnetic resonance imaging (MRI) to aid therapeutic strategies. In earlier guidelines, MRI was contra-indicated in patients with CIEDs, mainly due to previous reports of severe complications. With the development of MRI-conditional CIEDs and recent evidence concerning non-MRI-conditional CIEDs, MRIs in CIED patients can be safely performed in many hospitals.However, there are several questions that need to be addressed. Which patients can we scan? How can the scans be performed safely? And last but not least, can cardiac MRI provide diagnostic yield in patients with CIEDs?Current European guidelines are rather outdated and vague about patient selection and practical issues. There are national guidelines on this topic but several issues need extra attention and those are addressed in this point of view. It is important to create an environment with proper patient selection without unnecessary MRI scans in CIED patients, but also without unnecessary fear of complications, preventing access to MRI in patients who can benefit from this powerful diagnostic tool

Stochastic scheduling techniques for integrated optimization of catheterization laboratories and wards

In catheterization laboratories (cath labs), doctors are required to perform invasive cardiovascu-lar procedures under a variety of specific constraints .Patients undergoing a treatment in a cath lab, generally also require preparative and aftercare at one of the hospital's wards, which complicate the scheduling pro-cess significantly .Still, in practice, scheduling of procedures for cath labs is mainly done by hand, which partly can be explained by the fact that many models make simplistic assumptions that ignore the actual practical complexity of the problem, such as the inherent randomness. In this paper, we propose an Integer Linear Programming based technique that integrates optimization for both cath labs and wards, while incorporating randomness within the scheduling process .Since the natural objective function is non-linear, the key insight for applying this method is that the objective function can be linearized under specific assumptions . These models have been tested on a case study of the VU Medical Center, for which the results are shown to be effective, as useful blueprints for the daily schedules are generated according to the preference of the hospital

Feature tracking compared with tissue tagging measurements of segmental strain by cardiovascular magnetic resonance

BACKGROUND: Left ventricular segmental wall motion analysis is important for clinical decision making in cardiac diseases. Strain analysis with myocardial tissue tagging is the non-invasive gold standard for quantitative assessment, however, it is time-consuming. Cardiovascular magnetic resonance myocardial feature-tracking (CMR-FT) can rapidly perform strain analysis, because it can be employed with standard CMR cine-imaging. The aim is to validate segmental peak systolic circumferential strain (peak SCS) and time to peak systolic circumferential strain (T2P-SCS) analysed by CMR-FT against tissue tagging, and determine its intra and inter-observer variability. METHODS: Patients in whom both cine CMR and tissue tagging has been performed were selected. CMR-FT analysis was done using endocardial (CMR-FT(endo)) and mid-wall contours (CMR-FT(mid)). The Intra Class Correlation Coefficient (ICC) and Pearson correlation were calculated. RESULTS: 10 healthy volunteers, 10 left bundle branch block (LBBB) and 10 hypertrophic cardiomyopathy patients were selected. With CMR-FT all 480 segments were analyzable and with tissue tagging 464 segments. Significant differences in mean peak SCS values of the total study group were present between CMR-FT(endo) and tissue tagging (-23.8 ± 9.9% vs -13.4 ± 3.3%, p < 0.001). Differences were smaller between CMR-FT(mid) and tissue tagging (-16.4 ± 6.1% vs -13.4 ± 3.3%, p = 0.001). The ICC of the mean peak SCS of the total study group between CMR-FT(endo) and tissue tagging was low (0.19 (95%-CI-0.10-0.49), p = 0.02). Comparable results were seen between CMR-FT(mid) and tissue tagging. In LBBB patients, mean T2P-SCS values measured with CMR-FT(endo) and CMR-FT(mid) were 418 ± 66 ms, 454 ± 60 ms, which were longer than with tissue tagging, 376 ± 55 ms, both p < 0.05. ICC of the mean T2P-SCS between CMR-FT(endo) and tissue tagging was 0.64 (95%-CI-0.36-0.81), p < 0.001, this was better in the healthy volunteers and LBBB group, whereas the ICC between CMR-FT(mid) and tissue tagging was lower. The intra and inter-observer agreement of segmental peak SCS with CMR-FT(mid) was lower compared with tissue tagging; similar results were seen for segmental T2P-SCS. CONCLUSIONS: The intra and inter-observer agreement of segmental peak SCS and T2P-SCS is substantially lower with CMR-FT(mid) compared with tissue tagging. Therefore, current segmental CMR-FT(mid) techniques are not yet applicable for clinical and research purposes