Cardiovascular Journal of Africa: Vol 32 No 5 (SEPTEMBER/OCTOBER 2021)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 32, No 5, September/October 2021 AFRICA 251 On the molecular level, there are a few changes that create an environment for spontaneous depolarisation of the ventricular myocytes. These include hypokalaemia, hypomagnesaemia, and excess calcium and catecholamine levels. 7 Several models show an indirect relationship between elevated LV filling pressure and PVC burden. Park et al . 8 showed frequent PVC is associated with left atrial enlargement in patients with normal LVEF. Left atrial (LA) size reflects the severity and chronicity of abnormal LV filling pressure. 9 Takahashi et al . 10 studied 109 patients (48 males, age 60 ± 19 years) with frequent monomorphic PVCs and no structural heart disease. The LV inflow diastolic filling velocity was recorded by transthoracic echocardiography (TTE) at the time of the PVCs in all patients. A total of 38 patients (35%) had PVC-related symptoms (19 with palpitations, 12 with pulse deficit, six with shortness of breath, six with malaise, one with syncope). These patients showed reduced PVC E-wave flow (9.3 ± 6.0 vs 14.6 ± 6.5 cm, p < 0.0001) and reduced PVC stroke volume (20.5 ± 10.8 vs 29.9 ± 17.2 ml, p = 0.0030). E/e ′ is generally the most feasible and among the most reproducible methods for estimation of filling pressure, which has become central in the guidelines for diastolic evaluation. 11 Several prominent validation studies have confirmed the correlation of this ratio with filling pressure, and the prediction of normal and abnormal filling pressure is most reliable when the ratio is less than eight or more than 15. Recently, E/e ′ has been correlated with ambulatory measurement of LA pressure in 60 simultaneous studies, with an area under the receiver operating characteristic (ROC) curve > 0.9127. Our results showed that the mean LVEDV and LVESV were significantly higher in the cases than the controls ( p = 0.019 and 0.023, respectively). Moreover, the mean E/E ′ was significantly higher in the cases than the controls ( p = 0.044). The correlation analysis showed a statistically significant correlation between percentage PVC (PVC%) and LVEDD, LVESV and E/E ′ . In concordance with our findings, Zaborska and colleagues conducted a prospective study on 40 consecutive patients with frequent, idiopathic PVC in order to evaluate the haemodynamics during PVC using echocardiography. The results showed a correlation between LVESV and PVC% ( r = 0.65, p < 0.01). 12 Similarly, Park and colleagues recruited 146 patients with frequent PVCs and normal LVEF to identify early cardiac structural/functional manifestations of frequent PVCs. Patients with PVCs had a statistically significant higher LVEDV and LVESV, whereas the E/E ′ was not significantly different. 8 Researchers in the past few decades have shown great interest in the effect of PVCs on the myocardium. The concept of PVC-induced cardiomyopathy has emerged dramatically since its proposal by Duffee et al . in 1998, when pharmacological suppression of PVCs in patients with presumed idiopathic dilated cardiomyopathy substantially improved LV systolic dysfunction. 13 The current body of evidence shows that PVC is an under- appreciated cause of LV dysfunction. Patients with PVCs may have no underlying structural heart disease and subsequently develop LV dysfunction and dilated cardiomyopathy. Moreover, in cases of those with an already impaired LV function from underlying structural heart disease, worsening of LV function may occur. 14 Although our results show that there was no significant difference between the two groups in the study in terms of LVEF measured by biplane planimetry, there was a statistically significant inverse correlation between PVC% and LVEF by biplane imaging ( r = –0.367, p < 0.001). In agreement with our findings, Niwano and colleagues conducted a prospective study on 231 consecutive patients presenting with frequent PVCs (> 1 000 beats/day) without any detectable heart disease or structural heart disease. The results demonstrated progressive worsening of LV function in patients with frequent PVCs (> 1 000 beats/day) as measured by LVEF over a follow-up period of four to eight years; there was a significant negative correlation between PVC prevalence and LVEF. Additionally, PVC% was considered an independent predictor for future development of LV systolic dysfunction. 9 In addition, Xu and colleagues performed a prospective study on 112 consecutive patients with PVCs to investigate the effect of burden and origin sites on LV function. Patients with frequent PVCs had higher LVEDD and LVESD but lower LVEF than patients with low burden of PVCs. 9 Similarly, Park and colleagues reported that logistic regression showed that PVCs% was an independent predictor of LVEF. 8 Kanei and colleagues included 108 patients with frequent right ventricular outflow tract PVCs on a 24-hour Holter monitor who had had a recent evaluation for LV dysfunction. The logistic regression analysis, using more than 10 000 PVCs, showed that the presence of non-sustained ventricular tachycardia was the only predictor of LV dysfunction. 15 A similar finding was observed by Baman and colleagues in a study that included 174 patients referred for ablation of frequent idiopathic PVCs. The results showed that patients with a decreased LVEF had a higher mean PVC burden compared with those with normal LVEF ( p < 0.0001). In a multivariate analysis, PVC burden was independently associated with reduced LVEF. 16 More recently, Dukes and co-workers studied 1 139 participants randomly assigned to 24-hour Holter monitoring with a normal LVEF over a median follow up of over 13 years. The results showed that patients within the highest quartile of PVC burden had a higher risk of decreased LEFV. Those in the upper quartile versus the lowest quartile of PVC burden had a multivariable adjusted three-fold greater odds of a five-year LVEF decline. 17 On the other hand, the ROC curve in our study showed that, at a cut-off of > 4.2% per day, the PVC% yielded a sensitivity of 67% and specificity of 80% for the detection of reduced S ′ . Despite these significant findings, the exact underlying mechanism of reduced LVEF in PVC is not entirely clear. From a cellular perspective, the mechanisms of PVC-induced LV dysfunction are speculative and based on animal models. It was postulated that the prolongation and marked beat-to-beat variation in action potential duration as well as decreased outward and inward (L-type calcium) currents could result in increased repolarisation heterogeneity. This may be associated with an increased risk of sudden cardiac death due to triggered activity and malignant ventricular arrhythmias. 18 It was also postulated that the contractile dysfunction observed in PVC-induced cardiomyopathy could be explained by an altered calcium- induced calcium release from the sarcoplasmic reticulum. 19 From a clinical perspective, the mechanical ventricular dyssynchrony resulting from the abnormal electrical ventricular activation may be a more straightforward explanation. Normal ventricular function relies on a synchronous activation of the