Ventricular arrhythmias are common in patients with advanced heart failure, with a prevalence of up to 33% in chronic ambulatory patients and it predict increased mortality from HF [9]. pre-operative ventricular arrhythmias were noted in Up to 45% in patients supported with a left ventricular assist device (LVAD) [10].
The aim of the current study was to determine the prevalence of silent VAs in ambulatory clinically stable HFrEF patients and its correlation to the outcome (death, HF hospitalization and sustained VT).
This study revealed that PVCs were detected during ambulatory ECG monitoring in 304 patients (76%), among which, 108 patients (27%) had infrequent PVCs (less than 5% of the total beats) and 196 patients (49%) had frequent PVCs (5% or more of the total beats). Among the frequent PVCs group, 94 patients (47.95%) had a single or multiple runs of NSVT. Sustained VT was not recorded in any of the studied patients during the ambulatory ECG monitoring period.
Regarding the relation of PVC frequency and the underlying substrate, we observed that among the ICM group (the great majority of our study patients), infrequent PVCs were detected in 84 patients (35.6%) while frequent PVCs in 152 patients (64.4%). Among the NICM group, infrequent PVCs were observed in 24 patients (35.3%), while 44 patients (64.7%) had frequent PVCs. PVCs were common finding in HFrEF patients regardless the etiology.
Podrid et al. [11] conducted a systematic review which included 13 studies. The overall number of patients included were 1322 patients. The authors showed that PVCs are particularly frequent in those who had CHF regardless the etiology (i.e., ischemic vs non-ischemic causes). Almost 80% of CHF patients had frequent PVCs whereas more than 40% had runs of NSVT.
In our study, we observed that in patients (Group A) with severely reduced LV systolic function (EF < 30%), frequent PVCs were detected in 28 patients (57.1%). While among patients with LVEF ≥ 30% (Group B), frequent PVCs were detected in 21 patients (42.9%).
Boas et al. [12], examined both the prevalence and prognostic significance of ventricular arrhythmias in 850 non-ischemic systolic HF patients with LVEF ≤ 35% and elevated natriuretic peptides. They performed a 24-h Holter monitor for all patients looking for NSVT, low PVCs burden (< 30 per hour) and high PVCs burden (≥ 30 per hour). In total, 193 patients died, 49 from sudden cardiac death (SCD) and 125 from cardiovascular death (CVD). NSVT, observed in 365 patients, was significantly associated with increased all-cause mortality. High PVC burden, found in 352 patients, was associated with increased all-cause mortality. There was no statistically significant association with SCD for neither NSVT nor PVC. In interaction analyses, neither NSVT (P = 0.56) nor high burden of PVC (P = 0.97) was associated with survival benefit from ICD implantation.
Our study showed a statistically significant association between the occurrence of major cardiovascular events (total mortality, hospitalization by HF and sustained VT) and the PVCs burden on Holter monitoring (P value = 0.008).
Saito [13] et al. examined the factors that predict ventricular arrhythmias (VAs) in the late phase (≥ 7 days) after acute myocardial infarction (AMI). They included 136 consecutive patients with an LVEF of ≤ 40% after AMI. The average LVEF at admission was 32.7 ± 8.2%. During a mean follow-up period of 20.7 months, 14 patients (10%) experienced lethal VAs, including VF (n = 8) and sustained VT (n = 10). Both age and the admission LVEF predicted lethal VAs on univariate analyses. Receiver operating characteristic curve analysis showed a LVEF cut-off value of 23% predicted the primary endpoint (area under the curve: 0.77, P < 0.0001). Furthermore, LVEF at admission independently predicted the primary endpoint (risk ratio = 7.12, P = 0.001) on multivariable analysis.
In contrast, other studies had reported no such relation between VAs and SCD. In one report involving 77 patients with CHF, the presence of NSVT on ambulatory monitoring was more common in those with the greatest degree of LV dysfunction and symptomatic CHF [14]. However, NSVT was not independently associated with SCD.
Teerlink et al. [15] examined the independent predictive value of VAs for SCD and all-cause mortality in PROMISE (Prospective Randomized Milrinone Survival Evaluation) trial. They included 1080 patients (NYHA class III/IV) and the LVEF < 35%. VAs were analyzed and quantified by the use of a baseline ambulatory ECGs. The frequency of NSVT was the most powerful predictor and remained a significant independent predictor when included with other clinical variables in the multivariate models of both sudden death mortality and non–sudden death mortality.
Lip et al. had published an interesting paper on arrhythmias in HF. They reported that VAs were frequently seen as the cause of sudden death or resuscitated sudden death in CHF. Indeed, 50% of all deaths in advanced CHF were sudden and the assumption had been that a significant proportion of these were due to VT/VF. As the severity of CHF increases, the percentage of deaths described as sudden decreases although the absolute risk of VAs and sudden death probably continues to increase [16].
In the current study, a multivariate analysis included the following variables (Age, PR interval, QRS duration, bundle branch pattern, LVEF and PVC burden), revealed that LVEF and the PVCS burden were independent predictors of major adverse cardiovascular events (death, HF hospitalization and sustained VT).
We strongly believe that a lot of research is still needed to understand the predictors of prognosis in heart failure (HF) patients, especially the compensated clinically stable patients, and to better stratify them in order to improve the high morbidity and mortality rates. Our study highlighted the importance of through assessment of such a cohort of asymptomatic HFrEF patients searching for silent arrhythmias.
Limitations
The number of patients enrolled in this study represented a limitation together with the predominance of the male gender and the relatively short follow-up duration.
