Literature Review – Left Ventricular Activation Time
Defining the left ventricular activation time
Heart failure has exposed majority of the patients to succumbing during cardiac operations. As the heart is divided of four chambers, the coordination of system is essential to the wellbeing of patients or any other individual. According to Hang Zhang et al. (2013), medical practitioners devolve their expertise in controlling the response rate of ventricular lead with a lead in electrical fallacy prompting to delayed resynchronization of the left ventricle. As conceptualized through dyssynchronous mechanical activation of the left ventricle, the case could also emerge from the effects of the Left bundle branch block (LBBB). Usually, the Left bundle branch block is associated with electrical remodelling and progressive dilation especially in patients diagnosed with heart failure. Cardiac function can be improved using the cardiac resynchronization therapy.
Therefore, left ventricular activation time exists in the event of increased angiotensin II with a similar increment in the patient’s aldesterone levels causing simultaneous impulses, vasoconstriction, and alterations of the ventricle’s hemodynamic rate. According to Charlotte et al. (2011), cardiac resynchronization therapy is usually done to synchronize the contraction within the left ventricle, between the left and right ventricles, as well as between the ventricles and the atria. Other than improving the cardiac function, the Cardiac resynchronization therapy is also known to improve the quality of the patient’s life and increase the chances of survival (2).
The resynchronization concept also seems to be applicable to a patient, suffering from heart failure, who is chronically right ventricular paced and show dyssynchronous mechanical activation that is iatrogenic induced. According to (3, p. 445) even though the Cardiac resynchronization therapy improves electrical and left ventricular mechanical synchrony and reverses left ventricular remodelling in a patient who was chronically right ventricular paced prior to the Cardiac resynchronization therapy, its effectiveness in such a patient is not as certain.
This research was conducted to determine the predictive value of baseline left ventricular activation time on the clinical outcome, which is long term, in a population of patients under the cardiac resynchronization therapy. We were also aiming at determining if the baseline left ventricular activation time has the same predictive value in patients who were chronically paced verses those who were not chronically paced before the Cardiac resynchronization therapy. We had the hypotheses that the time to intrinsicoid deflection in a lateral electrocardiogram leads is an electrocardiogram predictor of the left ventricular reverse remodelling after undergoing the Cardiac resynchronization therapy in patients with heart failure.
This research was carried out in compliance with the Declaration of Helsinki. We sought approval of the protocol from the local ethics committee and obtained an informed consent from each of the patients who were studied. The patients who were studied had left ventricular ejection fraction values less than or equal to 0.35, QRS durations that were greater than or equal to 120ms and diagnosed with either the New York Heart Association III or IV symptoms. This was despite the optimal medical therapy that had undergone a successful Cardiac resynchronization therapy implantation within the ninety month period between April of 1999 and October 2006. The analysis included two hundred and nineteen patients with non-ischemic or ischemic cardio-myopathy. There was also a set condition that each of the patients had to have a pre and post implantation electrocardiograms accessible for reviews and were part of the analysis.
An analysis of the left bundle branch block activation sequence, paced activation sequence and their interaction can be used to predict reverse remodelling. Since the extent of long term left ventricle reverse remodelling during mid-term follow up has been associated with long term outcome (9, p. 437), then potential prediction of the long term outcome can be assumed. However, the analysis conducted by (10, p. 244-358) is rather difficult to adopt in a daily clinical routine because of its complexity. This is contrary to the measurement of the maximum left ventricle activation time is a simple and easily assessed parameter. Although the left ventricular activation time is known to predict remodelling after cardiac resynchronization therapy, its effect on the long term clinical outcome is not known.
Furthermore, the relationship between the left ventricular activation time and the left ventricular lead position has never been assessed even though it might be important. The left ventricular activation time was linked with significantly lower risks of transplant or death in unpaced patients. Patients diagnosed with RBBB morphology, and those with right ventricular pacing showed no relationship between the left ventricular activation time and the outcome. This relation was not affected by the QRS duration time or the left ventricular lead position. The number of patients with anterior lead position was seemingly too low; hence more studies should be done to assess the influence of the left ventricular lead position.
Interrelation of the left ventricular activation time and heart failure
According to the contextualized study by Ploux et al. (2013), electrical dyssychrony is indicated by the prolongation of QRS as measured on surface electrocardiogram thus making it the main approach of identifying left ventricular time and heart failure through cardiac resynchronization therapy candidates. Further, the research asserts that the standard criterion for selection of Cardiac resynchronization therapy is fulfilled; at least thirty percent of the patients do not get significant benefits. It is idealized that the differences in the BNP (B-type Natriuretic Peptide) and ANP (A-type Natriuretic Peptide) lead to vasoconstriction of left ventricular blood vessels resulting to cardiac infarction. Since the circumstances emanate from myocardial injury which simultaneously reduces cardiac output, it is indicated the subsequent developments in SNS and RAAS are evident. RAAS (renin angiotensin aldosterone system) prompts increased vasoconstriction and hemodynamic alterations because of angiotensin II and aldosterone respectively.
With an increased preload and afterload, the left ventricular negative is experienced; hence, increased left ventricular activation time leading to heart failure. Since the delayed left ventricular activation time can be obtained from the simple measurement of the electrocardiogram, the baseline electrocardiogram is considered to be a potential predictor of the patient’s response to the Cardiac resynchronization therapy. Though, the parameter has been validated only over a follow-up in unpaced patients which was short term. For this reason, it is not known whether this particular parameter equally compares equally in predictive value in right ventricular paced patients and whether the value predicted relates to the clinical outcome, which is rather long term, irrespective of the QRS duration and the left ventricular lead position (5).
The recommended supine twelve-lead surface electrocardiograms (25mm/s, 10mm/mV) were before and after Cardiac resynchronization therapy implantation were analysed. The analysis was blinded to the outcome results using digital callipers at a magnification of 200% with a specific calibration for 25mm/s paper speed. Paced or intrinsic QRS durations were measured using the widest QRS complex in all leads. QRS shortening (QRSpre – QRSpost >0) may or may not be brought about by Biventricular stimulation. The QRS axis was identified as: right axis deviation (-90 to 800), the normal frontal plane axis (-30 to 900) and the left axis deviation (-30 to -900). We defined the left bundle branch block as a maximum QRS value greater than or equal to 120ms with a QS or rS pattern in lead V1 concurring with the coexisting R wave but no Q wave in either the lead I or V6. The right bundle branch block criterion includes a QRS value that is greater than or equal to 120ms with a wide R prime (Ŕ) in lead V1 and a wide terminal S wave in leads V6 and I.
Eitel et al. (2012) study’s analyses of left ventricular and right ventricular activation times from baseline electrocardiograms were run as per the previous description. Briefly, the period (ms) between the QRS onset and the first notch in the greater than or equal to 2 adjacent leads were measured as Right ventricular activation time. Although the notches in the initial 40ms of the S wave in V2 and V1 leads were excluded. In right ventricular paced patients, the measurements were taken beginning from the right ventricular pacemaker stimulus. The left ventricular activation time was calculated by subtracting the Right Ventricular activation time for each lead from the QRS duration. This calculation enabled us to determine the longest left ventricular activation time. There was a necessity to use linear regression to estimate the longest left ventricular activation time for five patients because it could not be determined.
Inter quartile range, median or mean ± standard deviation were the main modes used to present continuous variables. The evaluation of the differences in continuous data was done using a Mann-Whitney U test. Fisher’s exact test was used to compare categorical data as recommended by (6). Unadjusted event rates were compared using the log rank test statistic. The multivariate and univariate association between outcome and the predictive value was assessed using the Cox models. The multivariate models included the following variables: gender, age, baseline LVEF, QRS duration, NYHA class, aetiology of left ventricular dysfunction, basal atrial fibrillation, medications and anterior lead position. The maximum left ventricular activation time was evaluated as a continuous variable for the assessment of biological plausibility. It was also assessed as dichotomised variable for use in clinical prediction. Previously published data was used as a baseline for choosing a previously defined left ventricular activation time cut-point of ≥125ms.
Important subgroups were established while the sample size was limited. The subgroups were left bundle branch block verses right bundle branch block, prior continuous right ventricular pacing verses intrinsic conduction. The subgroups were set up due to potential for modification effect by these particular variables. The product of left ventricular activation time and chronic right ventricular pacing was an evidence of multiplicative statistical interaction. The Kaplan-Meier method, recommended by (6) was used for presenting clinical outcomes. The eleventh version of stata was used to perform the analyses.
Left ventricular activation time studies
In explaining the interrelation between left ventricular activation and heart failure, Shetty et al. (2011) assumed immediate primary constituents to indicate the probability of the occurrences among participants. The first research emphasises that sixty nine percent of patients diagnosed with ischaemic cardiomyopathy suffer from increased LVAT and heart failure. Accordingly, the mean LVEF measurement was 23.2 ± 7.8%. 31% of the patients (sixty eight patients) had chronic right ventricular paced. Left bundle branch block was revealed in 79% of the patients (119) by a baseline-unpaced QRS. It also revealed the right bundle branch block in fourteen patients and unspecific intra-ventricular delay in conduction in twelve percent of the patients (14 patients). Right ventricular paced patients were paced the whole time (upper quartile 100%, lower quartile 100% and median 100%). These patients turned out to be older than the ones who were unpaced and they had a significantly higher rate of atrial fibrillation (P < 0.001) prior to the surgery. Right ventricular paced patients often had left axis deviation value of p < 0.001, a longer QRS duration of P < 0.001 and a baseline left ventricle activation time of P < 0.002.
According Ploux, et al. (2013), 12% of the patients (fourteen patients) implanted with cardiac resynchronization therapy implants suffer from left ventricular activation time hence heart failure. On the other hand, eighty eight percent of the patients had a cardiac resynchronization therapy defibrillator. LV lead position was classified as anterior, lateral and posterior in 9%, 51% and 41% of patients respectively. 9 % of the unpaced patients had anterior lead position and ten percent of the right ventricular paced patients. Prior to the Cardiac resynchronization therapy implantation, twenty eight percent of the patients had permanent atrial fibrillation.
Munoz et al. (2013) perceives that LVAT and subsequent heart failure cases are noticeable in 36% of the patients diagnosed with permanent atrial fibrillation had SR at follow up presentation. Out of the sixty six patients with atrial fibrillation, only two of them had the atrio-ventricular junction ablation. In general, LVAT prompts heart failure while patients with biventricular paces face greater challenges with a margin exceeding 90% (upper quartile 100%, lower quartile 94% and median 97%) according to the assessment using diagnostics devices and a twenty four hour ambulatory electrocardiogram monitoring. There was a similar high rate of biventricular pacing in patients with atrial fibrillation (upper quartile 100%, lower quartile 94% and median 97%).
According to Eitel et al. (2012), the research declares that a follow up of 56 months witnessed the death of ninety two patients and cardiac transplantation of ten patients. The outcome in right ventricular paced patients and unpaced patients was almost similar with 37% (twenty five patients) versus 44% (sixty seven patients) deaths and 4 (6%) versus 6 (4%) transplants. Similar to the results found by (7, p. 677-690), right ventricular pacing was not linked with any worse outcome post adjustments for gender, age, baseline LVEF, QRS duration, NYHA class, baseline atrial fibrillation, anterior lead position, medications and aetiology of left ventricular dysfunction. Therefore, the majority deaths in most of the groups were cardiovascular (seventy percent of deaths in non-paced groups and sixty eight percent deaths in right ventricular paced groups). The patients with right bundle branch block morphology experienced a higher transplantation or mortality rate, with cardiovascular deaths being cardiovascular. There was no difference in the number of deaths after the exclusion of patients with right bundle branch block morphology.
The findings of the research show that cardiac resynchronization therapy significantly reduces mortality among patients diagnosed with the sinus rhythm, QRS duration ≥ 120ms, NYHA class II-IV symptoms and LVEF ≤ 0.35. (8) Found that the effectiveness of cardiac resynchronization therapy among right ventricular paced patients is less clear. Right ventricular paced patients who underwent the cardiac resynchronization therapy were commonly older and had atrial fibrillation as compared to patients with primary cardiac resynchronization therapy. Chronic right ventricular pacing brings about a longer QRS duration and an extra placement of a left ventricular lead in reduction of QRS duration compared with unpaced patients.
- Bax J, Jesup M, Brugada J, Schalij M. Cardiac Resynchronization Therapy. CRC press; 2007.
- Crawford M. Cardiology. 3rd ed. Philadelphia: Mosby/Elsevier; 2016.
- Eitel C, Wilton SB, Switzer N, Cowan K, Exner DV. Baseline delayed left ventricular activation predicts long-term clinical outcome in cardiac resynchronization therapy recipients. Europace. 2012 Mar 1; 14(3):358-64.
- Mabezaa A. Acute Heart Failure. New York: London: Springer; 2008.
- Munoz FD, Powell BD, Cha YM, Wiste HJ, Redfield MM, Friedman PA, Asirvatham SJ. Delayed intrinsicoid deflection onset in surface ECG lateral leads predicts left ventricular reverse remodeling after cardiac resynchronization therapy. Heart Rhythm. 2013 Jul 31; 10(7):979-87.
- Ploux S, Lumens J, Whinnett Z, Montaudon M, Strom M, Ramanathan C, Derval N, Zemmoura A, Denis A, De Guillebon M, Shah A. Noninvasive electrocardiographic mapping to improve patient selection for cardiac resynchronization therapy: beyond QRS duration and left bundle branch block morphology. Journal of the American College of Cardiology. 2013 Jun 18; 61(24):2435-43.
- Shetty AK, Sohal M, Chen Z, Ginks MR, Bostock J, Amraoui S, Ryu K, Rosenberg SP, Niederer SA, Gill J, Carr-White G. A comparison of left ventricular endocardial, multisite, and multipolar epicardial cardiac resynchronization: an acute haemodynamic and electroanatomical study. Europace. 2014 Jun 1; 16(6):873-9.
- Yu C, Hayes D, Auricchio A. Cardiac Resynchronisation Therapy. 2nd ed. Malden, Mass: Blackwell Futura; 2009.
- Yu C, Hayes D, Auricchio A. Cardiac Resynchronization therapy. Malden, Mass: Blackwell pub; 2006.
- Zhang H, Dai Z, Xiao P, Pan C, Zhang J, Hu Z, Chen S. The Left Ventricular Lead Electrical Delay Predicts Response to Cardiac Resynchronisation Therapy. Heart, Lung and Circulation. 2013 Oct 31; 23(10):936-42.