605 Assessment of intracardiac flow dynamics for the evaluation of patients with cardiac resynchronization therapy

Aims Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure (HF), reduced left ventricular ejection fraction (EF ≤ 35%) and high-grade intraventricular conduction delays. CRT improves cardiac function, symptoms and well-being, and reduces morbidity and mortality in this setting. However, there are patients unresponsive to CRT. Responders show reverse ventricular remodelling, volumes and diameters reduction, and EF improvement. Noninvasive cardiovascular imaging for visualization and quantitation of intracardiac flows and turbulences has not been assessed thoroughly in CRT. This study seeks to evaluate if the quantitative analysis of intracardiac flow dynamics in HF patients treated by CRT might provide additional information for device optimization and clinical response. Methods and results Fifteen HF patients (five females, age 69.6 ± 9.4 years, NYHA class II/III, EF 29.3 ± 4.6%) were enrolled in the study. Eleven had primitive dilated cardiomyopathy and four had post-ischaemic etiology with completed revascularization. Pacemaker-dependent cases were excluded. MyLab™ X8 platform was used for echocardiographic assessment of intracardiac flow dynamics performed on apical three chamber views. All examinations were realized in baseline (active CRT) and after 5 min of biventricular pacing switch off. The hyperDoppler software was used to assess intracardiac vortexes properties. The analyzed parameters were: vortex area, vortex length, vortex depth, and kinetic of energy dissipation (ΔKE). Categorical variables are expressed as numbers and percentages. Quantitative variables are expressed as mean and standard deviation (SD). Shapiro–Wilk test, D’Agostino Pearson test, and visual inspection of Q–Q-plots were executed to evaluate if variables were normally distributed. Quantitative variables were evaluated with paired sample T-test or Wilcoxon test when appropriate. Clinical features, biochemical parameters, electrocardiograms with and without cardiac pacing, and EF before and after CRT implantation were collected. Although no difference was observed in vortex area/depth/length, a significant increase in KE dissipation after switching OFF the CRT devices (from 1.2 ± 0.9 to 3.5 ± 2.3 J, P < 0.03) was remarkably observed. According to EF improvement after CRT, the patients were divided in responders (5% increase in EF, N = 10) and non-responders (N = 5). Moreover, by analysing the extent of QRS dispersion and the variation of KE dissipation in spontaneous rhythm and after silencing the biventricular pacing, a positive ventricular remodelling (QRS 141.3 ± 29.3 vs. 154.4 ± 24.4ms, P = 0.02; KE dissipation 0.92 ± 0.87 J in responders and 1.53 ± 1.76 J in non-responders, P = 0.006) was detected in responders. Conclusions Noninvasive intracardiac flow dynamics in HF patients represents a complementary tool to standard echocardiography, and provides additional parameters for assessing prognosis and outcomes in CRT recipients. The impact of maladaptation in intracardiac flow dynamic on progressive LV remodelling could be useful to evaluate the prognostic meaning of implanted CRT device and to predict the response to device implantation, based on cardiac flow analysis.

555 Torsade-de-pointes electrical storm late after treatment with hydroxychloroquine and azithromycin for COVID-19

A 78-year-old woman was admitted to our hospital due to multiple brief episodes of transient loss of consciousness. She was recently hospitalized elsewhere for SARS-CoV-2 infection and she had been discharged two days before. During the previous hospitalization she had been treated with hydroxychloroquine 400 mg twice daily on Day 1, followed by Hydroxychloroquine 400 mg daily together with azithromycin 500 mg daily for 7 days, leading to symptomatic resolution and two consecutive negative RT-PCR tests at discharge. Her medical history included dilated cardiomyopathy and in 2017 she underwent CRT-D implantation for primary prevention; over the past 3 years, she did not experience any ICD intervention. Her home therapy included amiodarone, bisoprolol, warfarin, and trazodone. Baseline ECG obtained 6 month before admission is shown in Figure 1, Panel A. On admission, her ECG showed sinus bradycardia with biventricular pacing and significant QT prolongation (i.e. 640 ms, Figure 1 B). On day 2 of hospitalization, she reported multiple brief episodes of transient loss of consciousness. An interrogation of her device revealed 27 torsade-de-pointes episodes in a 48-hour period, treated with 11 shocks. All episodes were preceded by a variable period of bigeminal rhythm due to one or two premature ventricular beats coupled to the prolonged QT segment of the preceding basic beat in a ‘short-long-short’ sequence (Figure 2). The patient experienced a torsade-de-pointes TdP during COVID-19 disease. She had multiple concomitant factors for QT prolongation (TISDALE SCORE 13): mainly, female sex, cardiac disease, inflammation, electrolyte imbalances and multiple QT-prolonging drugs. Amiodarone and bisoprolol were subsequently stopped and potassium and magnesium were supplemented, with rapid resolution of torsade-de-pointes. No more episodes of TdP were detected after two weeks of hospitalization. The remote monitoring assessment of her device did not show any further episodes during subsequent follow-up. To our best knowledge, this is the first ICD-documented report of a TdP electrical storm in a COVID-19 patient, treated with HCQ/AZT, who had multiple concomitant factors for QT prolongation. 555 Figure 1

Pacemaker associated reduction of left ventricle systolic function

In recent years, data have been accumulated on the negative effect of right ventricular (RV) stimulation, leading to left ventricular (LV) asynchrony, proarrhythmias and progressive heart failure (HF). On the other hand, biventricular pacing has been shown to affect ventricular asynchrony, reduce HF manifestations, and improve prognosis in patients with LV dysfunction and wide QRS complex. The induced asynchrony from apical right ventricular pacing is unequivocally associated with changes in myocardial perfusion, LV dysfunction, and poorer prognosis for patients over time. This has led researchers for decades to look for an alternative position for electrode placement. The incidence of pacemaker-induced cardiomyopathy (PICM) ranges from 5.9 to 39% in patients with RV pacing, depending on the given definition and the limit for the degree of pacing. Upgrading to biventricular pacing has been shown to reverse the cardiomyopathy. Recently, there has been evidence of a positive effect of His bundle pacing (HBP) in the treatment of PICM even in patients with no improvement after biventricular pacing. The question about the pathogenetic mechanisms of PICM is currently unanswered. The connection between electrical asynchrony and the negative effect on cardiac pump function is clear. There is also evidence of an established relationship between asynchrony and coronary blood flow. The predisposing individual characteristics of the patient in which these negative effects are manifested are not clear. This is an issue that requires further studies.

Very Long-Term Follow-Up in Cardiac Resynchronization Therapy: Wider Paced QRS Equals Worse Prognosis

Background: Different electrocardiogram (ECG) findings are known to be independent predictors of clinical response to cardiac resynchronization therapy (CRT). It remains unknown how these findings influence very long-term prognosis. Methods and Results: A total of 102 consecutive patients (75 males, mean age 65 ± 10 years) referred to our center for CRT implantation had previously been included in this prospective observational study. The same patient group was now re-evaluated for death from all causes over a prolonged median follow-up of 10.3 years (interquartile range 9.4–12.5 years). During follow-up, 55 patients died, and 82% of the clinical non-responders (n = 23) and 44% of the responders (n = 79) were deceased. We screened for univariate associations and found QRS width during biventricular (BIV) pacing (p = 0.02), left ventricular (LV) pacing (p < 0.01), Δ LV paced–right ventricular (RV) paced (p = 0.03), age (p = 0.03), New York Heart Association (NYHA) class (p < 0.01), CHA2DS2-Vasc score (p < 0.01), glomerular filtration rate (p < 0.01), coronary artery disease (p < 0.01), non-ischemic cardiomyopathy (NICM) (p = 0.01), arterial hypertension (p < 0.01), NT-proBNP (p < 0.01), and clinical response to CRT (p < 0.01) to be significantly associated with mortality. In the multivariate analysis, NICM, the lower NYHA class, and smaller QRS width during BIV pacing were independent predictors of better outcomes. Conclusion: Our data show that QRS width duration during biventricular pacing, an ECG parameter easily obtainable during LV lead placement, is an independent predictor of mortality in a long-term follow-up. Our data add further evidence that NICM and lower NYHA class are independent predictors for better outcome after CRT implantation.

Single Centre Experience in Pediatric Pacing

Corresponding author [email protected] ( Hosny Hosny Elsayed Arafa) Background Permanent Pacemakers have a growing use in the pediatric population due to congenital and surgically acquired rhythm disturbances but they present unique problems and implications. Their implantation, follow up, the diversity and complexity of pediatric patients and congenital heart disease make device management a highly individualized art in pediatric pacing. Certain challenges are posed in adult-like somatic growth and active lifestyle susceptibility to infection and generally anticipated long survival. Objective The current study aims to present our institute's experience in pediatric and adolescent pacemaker implantation and long term outcome. Patients and Methods The study included 100 patients who have cardiac devices (permanent pacemaker)that were implanted in AinShams University and visit our patient clinic for regular programming during the period from July 2018 to December 2019. All patients were subjected to history taking, clinical examination, ECG recording then Echocardiography and device programming. Results The study included 100 patients,49 females and 51 males with a mean age of 13.12 ± 5.04. Patients weighted from 8 to 85 kg, measured from 40 to 185 cm in height. According to the mode of pacing, 67 were in the VVIR group while 33 in the DDDR group. According to the indication of pacing, two cases were due to sinus node dysfunction,52 due to congenital complete heart block and 46 due to postoperative CHB. 59 patients underwent cardiac surgery. 53 were admitted to CCU by syncope or presyncope. As Regards the complications,2 cases had superficial infection after 2 weeks relived by antibiotic, 2 patients suffered from pocket hematoma after 2 weeks, 10 cases of lead fracture from 1 to 8 years after implantation due to external trauma, 3 cases of lead dislodgment from 1 to 6 months postprocedure,1 case developed LV dysfunction and upgraded to CRT,1 case had psychological trauma and 3 cases had insulation breaks. The device with the longest longevity duration is Medtronic and Tendril leads had the most common complications. Conclusion Implantation of a pacemaker in children is generally safe. It could be justified to implant the pacemaker to improve the hemodynamic situation in individual patients or to consider biventricular pacing in LV dysfunctiont

Is there an antiarrhythmic benefit from switching to sacubitril/valsartan therapy? A systematic review and meta-analysis

Background Sacubitril/valsartan through reverse structural remodeling and neurohormonal inhibition could play an antiarrhythmic role. Purpose This systematic review and meta-analysis was performed to explore the arrhythmiologic effects of switching patients with heart failure with reduced ejection fraction (HFrEF) from angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) to sacubitril/valsartan. Methods We searched major databases for studies comparing device-detected, incident atrial and ventricular arrhythmias in patients with HFrEF while on ACEi/ARBs versus while on sacubitril/valsartan. For pooling the primary outcome of interest, we calculated the risk difference (RD) with the corresponding 95% confidence interval (CI) in the probability of experiencing each arrhythmic event while on ACEi/ARBs and while on sacubitril/valsartan. A random effects (DerSimonian-Laird) model was adopted. Results We analyzed 4 eligible studies, resulting in 497 patients with a pooled mean age of 67.8±10.36. 64% had ischemic cardiomyopathy while 98% had either an implantable cardioverter defribrillator or a cardiac resynchronization therapy device. Main comorbidities were hypertension (68.7%) and dyslipidemia (59.6%). Almost all (96.3%) patients were treated with b-blockers and 23.7% were also receiving anti-arrhythmic drugs, mainly amiodarone. After switching to sacubitril/valsartan there was a trend towards reduced risk for sustained ventricular tachycardia/fibrillation and non-sustained ventricular tachycardias (RD: −0.04, 95% CI: −0.09–0.02, I2: 65.7% and −0.06, 95% CI: −0.19–0.07, I2: 85%; respectively). Meta-regression analysis showed that patients with ischemic cardiomyopathy experience greater benefit. Incident paroxysmal atrial fibrillation/tachycardia was significantly reduced (RD: −0.09 95% CI: −0.14 to −0.03, I2: 0%), while favorable effects were noticed for the risk of appropriate shock delivery and inadequate biventricular pacing (RD: −0.06, 95% CI: −0.09 to −0.03, I2: 0% and −0.06, 95% CI: −0.11 to 0.00, I2: 35.55%, respectively). All results seem to suffer from publication bias. Conclusion Limited data support that switching to sacubitril/valsartan seems to be associated with reduced risk for both ventricular and atrial arrhythmias. More studies are needed to clarify the potential anti-arrhythmic role of this drug. Whether patients with frequent arrhythmias or at high arrhythmic risk may benefit from early switch is a matter of further investigation. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2