Enhancing Cardiac Pacing Strategies: A Review of Conduction System Pacing Compared to Right and Biventricular Pacing and their influence on myocardial function.

Traditional right ventricular pacing has been linked to the deterioration of both left ventricular diastolic and systolic function. This worsening often culminates in elevated rates of hospitalization due to heart failure, an increased risk of atrial fibrillation, and increased morbidity. While biventricular pacing has demonstrated clinical and echocardiographic improvements in patients afflicted with heart failure and left bundle branch block, it has also encountered significant challenges, such as a notable portion of non-responders and procedural failures attributed to anatomical complexities. In recent time, the interest has shifted towards conduction system pacing, initially His bundle pacing and more recently left bundle branch area pacing, as promising alternatives to the established methods. In contrast to other approaches, conduction system pacing offers the advantage of fostering more physiological and harmonized ventricular activation by directly stimulating the His-Purkinje network. This direct pacing results in a more synchronized systolic and diastolic function of left ventricle compared to right ventricular pacing and biventricular pacing. Of particular note is conduction system pacing's capacity to yield shorter QRS, conserve left ventricular ejection fraction, and reduced rates of mitral and tricuspid regurgitation when compared to right ventricular pacing. The efficacy of conduction system pacing has also been found to have better clinical and echocardiographic improvement than biventricular pacing in patients requiring cardiac resynchronization. This review will delve into myocardial function in conduction system pacing compared to right ventricular pacing and biventricular pacing.

Inappropriate Extravascular ICD Shock Due to Wet Car Seat.

Inappropriate shocks from an Intracardiac defibrillator are associated with increased mortality and may be caused by external electromagnetic interference. This case illustrates that water is an excellent conductor of electricity and that determined investigation may reveal the cause of inappropriate shocks.

Mechanical Dyssynchrony Combined with Septal Scarring Reliably Identifies Responders to Cardiac Resynchronization Therapy.

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74-0.88) and 0.86 (95%CI: 0.79-0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12-0.67) to 0.20 (95%CI: 0.08-0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine.

Determinants of the time-to-peak left ventricular dP/dt (Td) and QRS duration with different fusion strategies in cardiac resynchronization therapy.

Background: Cardiac resynchronization therapy (CRT) is helpful in selected patients; however, responder rates rarely exceed 70%. Optimization of CRT may therefore benefit a large number of patients. Time-to-peak dP/dt (Td) is a novel marker of myocardial synergy that reflects the degree of myocardial dyssynchrony with the potential to guide and optimize treatment with CRT. Optimal electrical activation is a prerequisite for CRT to be effective. Electrical activation can be altered by changing the electrical wave-front fusion resulting from pacing to optimize resynchronization. We designed this study to understand the acute effects of different electrical wave-front fusion strategies and LV pre-/postexcitation on Td and QRS duration (QRSd). A better understanding of measuring and optimizing resynchronization can help improve the benefits of CRT. Methods: Td and QRSd were measured in 19 patients undergoing a CRT implantation. Two biventricular pacing groups were compared: pacing the left ventricle (LV) with fusion with intrinsic right ventricular activation (FUSION group) and pacing the LV and right ventricle (RV) at short atrioventricular delay (STANDARD group) to avoid fusion with intrinsic RV activation. A quadripolar LV lead enabled pacing from widely separated electrodes; distal (DIST), proximal (PROX) and both electrodes combined (multipoint pacing, MPP). The LV was stimulated relative in time to RV activation (either RV pace-onset or QRS-onset), with the LV stimulated prior to (PRE), simultaneous with (SIM) or after (POST) RV activation. In addition, we analyzed the interactions of the two groups (FUSION/STANDARD) with three different electrode configurations (DIST, PROX, MPP), each paced with three different degrees of LV pre-/postexcitation (PRE, SIM, POST) in a statistical model. Results: We found that FUSION provided shorter Td and QRSd than STANDARD, MPP provided shorter Td and QRSd than DIST and PROX, and SIM provided both the shortest QRSd and Td compared to PRE and POST. The interaction analysis revealed that pacing MPP with fusion with intrinsic RV activation simultaneous with the onset of the QRS complex (MPP*FUSION*SIM) shortened QRSd and Td the most compared to all other modes and configurations. The difference in QRSd and Td from their respective references were significantly correlated (ß = 1, R = 0.9, p < 0.01). Conclusion: Pacing modes and electrode configurations designed to optimize electrical wave-front fusion (intrinsic RV activation, LV multipoint pacing and simultaneous RV and LV activation) shorten QRSd and Td the most. As demonstrated in this study, electrical and mechanical measures of resynchronization are highly correlated. Therefore, Td can potentially serve as a marker for CRT optimization.

Shortening of time-to-peak left ventricular pressure rise (Td) in cardiac resynchronization therapy.

AIMS: We tested the hypothesis that shortening of time-to-peak left ventricular pressure rise (Td) reflect resynchronization in an animal model and that Td measured in patients will be helpful to identify long-term volumetric responders [end-systolic volume (ESV) decrease >15%] in cardiac resynchronization therapy (CRT). METHODS: Td was analysed in an animal study (n = 12) of left bundle-branch block (LBBB) with extensive instrumentation to detect left ventricular myocardial deformation, electrical activation, and pressures during pacing. The sum of electrical delays from the onset of pacing to four intracardiac electrodes formed a synchronicity index (SI). Pacing was performed at baseline, with LBBB, right and left ventricular pacing and finally with biventricular pacing (BIVP). We then studied Td at baseline and with BIVP in a clinical observational study in 45 patients during the implantation of CRT and followed up for up to 88 months. RESULTS: We found a strong relationship between Td and SI in the animals (R = 0.84, P < 0.01). Td and SI increased from narrow QRS at baseline (Td = 95 ± 2 ms, SI = 141 ± 8 ms) to LBBB (Td = 125 ± 2 ms, SI = 247 ± 9 ms, P < 0.01), and shortened with biventricular pacing (BIVP) (Td = 113 ± 2 ms and SI = 192 ± 7 ms, P < 0.01). Prolongation of Td was associated with more wasted deformation during the preejection period (R = 0.77, P < 0.01). Six patients increased ESV by 2.5 ± 18%, while 37 responders (85%) had a mean ESV decrease of 40 ± 15% after more than 6 months of follow-up. Responders presented with a higher Td at baseline than non-responders (163 ± 26 ms vs. 121 ± 19 ms, P < 0.01). Td decreased to 156 ± 16 ms (P = 0.02) with CRT in responders, while in non-responders, Td increased to 148 ± 21 ms (P < 0.01). A decrease in Td with BIVP to values similar or below what was found at baseline accurately identified responders to therapy (AUC 0.98, P < 0.01). Td at baseline and change in Td from baseline was linear related to the decrease in ESV at follow-up. All-cause mortality was high among six non-responders (n = 4), while no patients died in the responder group during follow-up. CONCLUSIONS: Prolongation of Td is associated with cardiac dyssynchrony and more wasted deformation during the preejection period. Shortening of a prolonged Td with CRT in patients accurately identifies volumetric responders to CRT with incremental value on top of current guidelines and practices. Thus, Td carries the potential to become a biomarker to predict long-term volumetric response in CRT candidates.

Lateral Wall Dysfunction Signals Onset of Progressive Heart Failure in Left Bundle Branch Block.

OBJECTIVES: This study sought to investigate if contractile asymmetry between septum and left ventricular (LV) lateral wall drives heart failure development in patients with left bundle branch block (LBBB) and whether the presence of lateral wall dysfunction affects potential for recovery of LV function with cardiac resynchronization therapy (CRT). BACKGROUND: LBBB may induce or aggravate heart failure. Understanding the underlying mechanisms is important to optimize timing of CRT. METHODS: In 76 nonischemic patients with LBBB and 11 controls, we measured strain using speckle-tracking echocardiography and regional work using pressure-strain analysis. Patients with LBBB were stratified according to LV ejection fraction (EF) ≥50% (EFpreserved), 36% to 49% (EFmid), and ≤35% (EFlow). Sixty-four patients underwent CRT and were re-examined after 6 months. RESULTS: Septal work was successively reduced from controls, through EFpreserved, EFmid, and EFlow (all p < 0.005), and showed a strong correlation to left ventricular ejection fraction (LVEF; r = 0.84; p < 0.005). In contrast, LV lateral wall work was numerically increased in EFpreserved and EFmid versus controls, and did not significantly correlate with LVEF in these groups. In EFlow, however, LV lateral wall work was substantially reduced (p < 0.005). There was a moderate overall correlation between LV lateral wall work and LVEF (r = 0.58; p < 0.005). In CRT recipients, LVEF was normalized (≥50%) in 54% of patients with preserved LV lateral wall work, but only in 13% of patients with reduced LV lateral wall work (p < 0.005). CONCLUSIONS: In early stages, LBBB-induced heart failure is associated with impaired septal function but preserved lateral wall function. The advent of LV lateral wall dysfunction may be an optimal time-point for CRT.

Imaging predictors of response to cardiac resynchronization therapy: left ventricular work asymmetry by echocardiography and septal viability by cardiac magnetic resonance.

AIMS: Left ventricular (LV) failure in left bundle branch block is caused by loss of septal function and compensatory hyperfunction of the LV lateral wall (LW) which stimulates adverse remodelling. This study investigates if septal and LW function measured as myocardial work, alone and combined with assessment of septal viability, identifies responders to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: In a prospective multicentre study of 200 CRT recipients, myocardial work was measured by pressure-strain analysis and viability by cardiac magnetic resonance (CMR) imaging (n = 125). CRT response was defined as ≥15% reduction in LV end-systolic volume after 6 months. Before CRT, septal work was markedly lower than LW work (P < 0.0001), and the difference was largest in CRT responders (P < 0.001). Work difference between septum and LW predicted CRT response with area under the curve (AUC) 0.77 (95% CI: 0.70-0.84) and was feasible in 98% of patients. In patients undergoing CMR, combining work difference and septal viability significantly increased AUC to 0.88 (95% CI: 0.81-0.95). This was superior to the predictive power of QRS morphology, QRS duration and the echocardiographic parameters septal flash, apical rocking, and systolic stretch index. Accuracy was similar for the subgroup of patients with QRS 120-150 ms as for the entire study group. Both work difference alone and work difference combined with septal viability predicted long-term survival without heart transplantation with hazard ratio 0.36 (95% CI: 0.18-0.74) and 0.21 (95% CI: 0.072-0.61), respectively. CONCLUSION: Assessment of myocardial work and septal viability identified CRT responders with high accuracy.

Acute redistribution of regional left ventricular work by cardiac resynchronization therapy determines long-term remodelling.

AIMS: Investigating the acute impact of cardiac resynchronization therapy (CRT) on regional myocardial work distribution in the left ventricle (LV) and to which extent it is related to long-term reverse remodelling. METHODS AND RESULTS: One hundred and thirty heart failure patients, referred for CRT implantation, were recruited in our prospective multicentre study. Regional myocardial work was calculated from non-invasive segmental stress-strain loop area before and immediately after CRT. The magnitude of volumetric reverse remodelling was determined from the change in LV end-systolic volume, 11 ± 2 months after implantation. CRT caused acute redistribution of myocardial work across the LV, with an increase in septal work, and decrease in LV lateral wall work (all P < 0.05). Amongst all LV walls, the acute change in work in the septum and lateral wall of the four-chamber view correlated best and significantly with volumetric reverse remodelling (r = 0.62, P < 0.0001), with largest change seen in patients with most volumetric reverse remodelling. In multivariate linear regression analysis, including conventional parameters, such as pre-implant QRS morphology and duration, LV ejection fraction, ischaemic origin of cardiomyopathy, and the redistribution of work across the septal and lateral walls, the latter appeared as the strongest determinant of volumetric reverse remodelling after CRT (model R2 = 0.414, P < 0.0001). CONCLUSION: The acute redistribution of regional myocardial work between the septal and lateral wall of the LV is an important determinant of reverse remodelling after CRT implantation. Our data suggest that the treatment of the loading imbalance should, therefore, be the main aim of CRT.

An image fusion tool for echo-guided left ventricular lead placement in cardiac resynchronization therapy: Performance and workflow integration analysis.

BACKGROUND: The response rate to cardiac resynchronization therapy (CRT) may be improved if echocardiographic-derived parameters are used to guide the left ventricular (LV) lead deployment. Tools to visually integrate deformation imaging and fluoroscopy to take advantage of the combined information are lacking. METHODS: An image fusion tool for echo-guided LV lead placement in CRT was developed. A personalized average 3D cardiac model aided visualization of patient-specific LV function in fluoroscopy. A set of coronary venography-derived landmarks facilitated registration of the 3D model with fluoroscopy into a single multimodality image. The fusion was both performed and analyzed retrospectively in 30 cases. Baseline time-to-peak values from echocardiography speckle-tracking radial strain traces were color-coded onto the fused LV. LV segments with suspected scar tissue were excluded by cardiac magnetic resonance imaging. The postoperative augmented image was used to investigate: (a) registration accuracy and (b) agreement between LV pacing lead location, echo-defined target segments, and CRT response. RESULTS: Registration time (264 ± 25 seconds) and accuracy (4.3 ± 2.3 mm) were found clinically acceptable. A good agreement between pacing location and echo-suggested segments was found in 20 (out of 21) CRT responders. Perioperative integration of the proposed workflow was successfully tested in 2 patients. No additional radiation, compared with the existing workflow, was required. CONCLUSIONS: The fusion tool facilitates understanding of the spatial relationship between the coronary veins and the LV function and may help targeted LV lead delivery.

Cardiac Mechanical Alterations and Genotype Specific Differences in Subjects With Long QT Syndrome.

OBJECTIVES: This study aimed to explore systolic and diastolic function and to investigate genotype-specific differences in subjects with long QT syndrome (LQTS). BACKGROUND: LQTS is an arrhythmogenic cardiac ion channelopathy that traditionally has been considered a purely electrical disease. The most commonly affected ion channels are the slow potassium channel, IKs (KCNQ1 gene/LQT1), and the rapid potassium channel, IKr (KCNH2 gene/LQT2). Recent reports have indicated mechanical abnormalities in patients with LQTS. METHODS: We included 192 subjects with genotyped LQTS (139 LQT1, 53 LQT2). Healthy persons of similar age and sex as patients served as controls (n = 60). Using echocardiography, we assessed systolic function by left ventricular (LV) ejection fraction (EF), global longitudinal strain (GLS), and contraction duration (16 LV segments). Mechanical dispersion was calculated as standard deviation of contraction duration. Time difference between contraction duration and QT interval from electrocardiography (ECG) was defined as electromechanical time difference. We assessed diastolic function by transmitral filling velocities, early diastolic myocardial velocity (e'), and left atrial volume index (LAVI). Heart rate corrected QT interval (QTc) was assessed from 12-lead ECG. RESULTS: Systolic function by GLS was reduced in subjects with LQTS compared with healthy controls (-22.1 ± 2.1% vs. -23.0 ± 2.0%, p = 0.01), and GLS was worse in subjects with LQT2 compared with subjects with LQT1 (p = 0.01). Subjects with LQTS had longer contraction duration (426 ± 41 ms vs. 391 ± 36 ms, p < 0.001) and more dispersed contractions (33 ± 14 ms vs. 21 ± 7 ms, p < 0.001) compared with healthy controls. Diastolic function was also reduced in subjects with LQTS compared with healthy controls; e' was lower (10.7 ± 2.7 cm/s vs. 12.5 ± 2.0 cm/s, p < 0.001), and LAVI was increased (30 ± 8 ml/m(2) vs. 26 ± 5 ml/m(2), p = 0.01), also when adjusted for age and other possible confounders. CONCLUSIONS: Subjects with LQTS had a consistent reduction in both systolic and diastolic function compared with healthy controls. Differences in myocardial function between subjects with LQT1 and subjects with LQT2 may indicate that mechanical alterations in LQTS are genotype specific.

Reference interval for the index of coronary microvascular resistance.

AIMS: The index of microvascular resistance (IMR) is a relatively new tool that is used to assess microvascular function during routinely performed left heart catheterisations. In order to establish a reference interval for IMR, we investigated a subset of arrhythmia patients with structurally normal hearts and no or minimal coronary artery disease. METHODS AND RESULTS: Physiological variables, including IMR, were measured in 20 otherwise healthy patients aged 40-60 years (10 males and 10 females) who had been referred for electrophysiological evaluation of suspected atrioventricular nodal re-entry tachycardia. IMR values were non-normally distributed with a median value of 12.6. We established a reference interval, that would be relevant to 95% of the population, of 7.3 (90% CI: 6.6-8.0) - 27.2 (90% CI: 20.8-33.7), using Box-Cox transformation and the robust Horn method. Spearman's rank correlation analysis revealed no significant relationship between IMR and several different variables. CONCLUSIONS: A reference interval for IMR was established in a population of patients aged 40-60 years with structurally normal hearts, considered to be representative of the general population. IMR was not related to sex, age or any of the other variables tested, suggesting that this reference range can be applied to the general population.

Cardiac resynchronization by repositioning of a ventricular epicardial lead in a patient with hypoplastic left heart syndrome.

Patients with congenital heart disease and univentricular circulation are vulnerable to ventricular dysfunction. In the context of atrioventricular conduction defects, a ventricular pacemaker may be placed, possibly introducing dyssynchronous wall motion and deterioration of ventricular pump function. We describe such a case in which repositioning of the ventricular lead restored synchronicity.

Near-fatal outcome of late cardiac perforation by a pacemaker lead in a young woman with transposition of the great arteries.

We report a case of ventricular perforation by an active-fixation permanent pacemaker lead in a young woman with congenital heart defect and pacemaker because of atrioventricular block. The rarity of the case is based not only upon the late perforation (as opposed to the more common acute perforations) but also on the near-fatal outcome. The patient experienced sharp chest pain and 1 week later passed out with cardiac arrest.

Assessment of response criteria to cardiac resynchronization therapy (CRT) and prediction of response.

AIMS: Approximately 30% of patients treated with cardiac resynchronization therapy (CRT) do not respond. We evaluated response to CRT at six and 12 months, tested a novel response criterion and evaluated different clinical and echocardiographic predictors of response. METHODS AND RESULTS: Eighty one patients were enrolled. A definition of response to CRT was predefined as a combination of 1) a reduction of LV end-systolic volume of ≥10% and 2) either an improvement in NYHA class by ≥1 or an increase in peak oxygen consumption of ≥1 ml/kg/min. Pre-and postoperatively at six and 12 months we also evaluated the most commonly employed definitions of response in our material: NYHA class, quality of life, left ventricular (LV) performance and functional capacity. After six and 12 months of CRT, 42 (52%) and 48 patients (59%) were responders, respectively. Employing different criteria, response ranged from 33-96% and 31-94% at six and 12 months, respectively. In our material a large pre-operative interventricular motion delay (IVMD) was a predictor of response to CRT (p<0.05). CONCLUSIONS: Fifty two percent and 59% were responders to CRT at six months and one year given a predefined novel endpoint. Different response criteria to CRT gave response rates ranging from 33-96% and 31-94% at six and 12 months, respectively. A large IVMD predicts response to CRT at six and 12 months.

[Catecholaminergic polymorphic ventricular tachycardia]. / Katekolaminerg polymorf ventrikkeltakykardi.

BACKGROUND: CPVT (catecholaminergic polymorphic ventricular tachycardia) is a condition characterized by syncopes and cardiac arrest that was first described in 1975. CPVT has later been classified as a genetic disease with a great risk for life-threatening arrhythmias that are mainly caused by mutations in the ryanodine receptor 2 gene. Starting with a case report, we present an overview of CPVT. MATERIAL AND METHODS: The literature reviewed was identified through a non-systematic search in PubMed. RESULTS: Diagnosing CPVT may be difficult, as resting ECG is normal and the syncopes may be misdiagnosed as epilepsy. Information about syncopes related to physical or emotional stress and occurrence of unexplained syncopes or cardiac arrest among family members, is important in the diagnostic evaluation. An exercise stress test often reveals the classical pattern of ventricular arrhythmias at heart rates above 100 beats/min. The diagnosis can be confirmed by genetic testing. By beta-blocker treatment and, if necessary, an ICD (implantable cardioverter defibrillator) the prognosis can be improved. INTERPRETATION: CPVT is a serious disease with a poor prognosis when left untreated. It is a rare but important differential diagnosis in young individuals with syncopes or cardiac arrest. Genetic screening of relatives has made it possible to identify mutation carriers in affected families in order to provide them with preventive therapy.

High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening.

AIM: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease predisposing to life-threatening arrhythmias. We aimed to determine the prevalence of arrhythmias and efficacy of beta-blocker treatment in mutation-positive family members diagnosed by cascade genetic screening. METHODS AND RESULTS: Relatives of six unrelated CPVT patients were tested for the relevant mutation in the ryanodine receptor-2 gene. Mutation carriers underwent an exercise test at inclusion time and 3 months after the initiation of beta-blocker therapy in the highest tolerable dose. The occurrence of ventricular premature beats, couplets, and non-sustained ventricular arrhythmias (nsVT) were recorded in addition to the heart rate at which they occurred. Thirty family members were mutation carriers and were followed for 22 (13-288) months. Previous undiagnosed CPVT-related symptoms were reported by eight subjects. Exercise test induced ventricular arrhythmias in 23 of the 30 mutation carriers. On beta-blocker treatment, exercise-induced arrhythmias occurred at a lower heart rate (117 +/- 17 vs. 135 +/- 34 beats/min, P = 0.02) but at similar workload (P = 0.78). Beta-blocker treatment suppressed the occurrence of exercise-induced nsVT in three of the four patients, while less severe arrhythmias were unchanged. One patient died during follow-up. CONCLUSION: Exercise test revealed a high prevalence of arrhythmias in CPVT mutation carriers diagnosed by cascade genetic screening. beta-Blocker therapy appeared to suppress the most severe exercise-induced arrhythmias, while less severe arrhythmias occurred at a lower heart rate.