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Kevin Vernooy

Publications and source records attributed to Kevin Vernooy.

13 recordsLinked to original sources
PubMed2006

Calculation of effective VV interval facilitates optimization of AV delay and VV interval in cardiac resynchronization therapy.

BACKGROUND: In hearts with left bundle branch block (LBBB), both atrioventricular (AV) delay and interventricular (VV) interval determine left ventricular (LV) pump function in cardiac resynchronization therapy (CRT). The optimal combination of AV delay and VV interval currently is determined by extensive hemodynamic testing. OBJECTIVES: The purpose of this study was to investigate whether the effective VV interval (VV(eff)) can be used to optimize AV delay and VV interval. METHODS: In eight canine hearts with chronic LBBB, LV pacing was performed at various AV delays as well as biventricular pacing at multiple AV delays and VV intervals. LV pump function was assessed from LVdP/dt(max) and stroke volume (conductance catheter). Interventricular asynchrony was calculated from the timing difference between upslope of LV and RV pressure curves. VV(eff) was defined as the time delay between activation of the RV apex and LV lateral wall, irrespective of the source of RV activation (RV pacing or intrinsic conduction). VV(eff) was determined from pacemaker settings and surface ECGs recorded during biventricular pacing at various AV delays (positive values denote LV preexcitation). RESULTS: For all animals, the relationship between VV(eff) and LVdP/dt(max) as well as LV stroke work was parabolic. Maximal improvement in LVdP/dt(max) was similar during LV pacing, simultaneous biventricular pacing, and sequential biventricular pacing and was obtained at similar values of VV(eff). VV(eff) was strongly correlated with interventricular asynchrony (R = 0.97 +/- 0.03). Optimum LVdP/dt(max) occurred at VV(eff) ranging from -24 to 12 ms (mean -6 +/- 13 ms). For each experiment, the optimal VV(eff) was virtually equal to the value halfway between its minimum (during LV pacing at short AV delay) and maximum (during LBBB) value (R = 0.91). CONCLUSION: Use of VV(eff) facilitates determination of the best combination of AV delay and VV interval during biventricular pacing. For each individual heart, VV(eff), resulting in optimum LV pump function, can be estimated using surface ECGs recorded during biventricular pacing.

Animals↗
PubMed2006

Genetic and biophysical basis for bupivacaine-induced ST segment elevation and VT/VF. Anesthesia unmasked Brugada syndrome.

BACKGROUND: Brugada syndrome is an inherited disease associated with sudden cardiac death. The electrocardiographic pattern associated with Brugada syndrome has been linked to the use of sodium channel blockers, including antiarrhythmics, trycyclics and anesthetics. OBJECTIVE: We report a case of bupivacaine-induced Brugada syndrome, in which we investigated the genetic, biophysical and path physiological mechanism involved. METHODS AND RESULTS: The patient developed a Brugada-like electrocardiographic pattern twice under the influence of bupivacaine. The first occurrence was accompanied by ventricular tachycardia (VT) which subsided after withdrawal of the anesthetic. The VT was also observed during co-administration of diltiazem and isosorbide-5-mononitrate, agents thought to facilitate ST segment elevation in the Brugada syndrome. Genetic analysis revealed a missense mutation in the alpha subunit of the cardiac sodium channel, SCN5A. Biophysical analysis by whole-cell patch-clamping revealed a reduction in sodium current as a result of the mutation. The study of bupivacaine in the wedge model revealed use-dependent changes in conduction, heterogeneous loss of the action potential dome in RV epicardium and phase 2 re-entry when the preparations were pretreated with low concentrations of the calcium channel blocker verapamil. CONCLUSION: Our findings indicate that bupivacaine may induce the electrocardiographic and arrhythmic manifestations of the Brugada syndrome in silent carriers of SCN5A mutations. The data have important implications in the management of patients who develop ST segment elevation when under the influence of anesthetics such as bupivacaine.

Anesthesia, General↗
PubMed2006

Pacing-induced dys-synchrony preconditions rabbit myocardium against ischemia/reperfusion injury.

BACKGROUND: Because increased mechanical load induces preconditioning (PC) and dys-synchrony increases loading in late-activated regions, we investigated whether dys-synchrony induced by ventricular pacing (VP) at normal heart rate leads to cardioprotection. METHODS AND RESULTS: Isolated working rabbit hearts were subjected to 35 minutes of global ischemia and 2 hours of reperfusion. Seven hearts underwent VP PC (3 periods of 5 minutes VP at the posterior left ventricular [LV] wall), 7 hearts underwent ischemic preconditioning (IPC) (3 periods of 5 minutes of global ischemia), and 9 hearts served as control (C). LV pressure and sonomicrometry were used to assess global hemodynamics and segment work (SW) and end-diastolic segment length (EDSL) in anterior and posterior LV myocardium. Myocardial release of lactate and expression of proBNP mRNA were determined to gain insight in molecular processes involved in VP PC (*P<0.05). Infarct size (triphenyl tetrazolium chloride staining) was 18.3+/-13.0% in group C, and was uniformly reduced in the VP PC and IPC groups (1.8+/-0.8%*, and 3.5+/-3.1%*, respectively; and not significant between VP PC and IPC). LV posterior wall pacing (VP PC group) increased EDSL (by 6.3+/-5.8%*) and SW (to 335+/-207%*) in the LV anterior wall, whereas posterior wall SW decreased to negative values (-23+/-63%*). LV pacing did not significantly change lactate release and coronary flow but significantly increased proBNP mRNA expression in both anterior and posterior myocardium as compared with controls. CONCLUSIONS: Intermittent dys-synchrony is equally cardioprotective as "classical" IPC. Stretch-mediated signaling is a more likely trigger for VP PC than ischemia. VP PC is potentially applicable in cardiac surgery.

Animals↗
PubMed2006

Ventricular remodeling during long-term right ventricular pacing following His bundle ablation.

To investigate ventricular remodeling during long-term right ventricular (RV) pacing after His bundle ablation (HBA) in patients with atrial arrhythmias, a retrospective analysis was performed on echocardiographic data from 45 patients (mean age 57 +/- 11 years) with atrial arrhythmias who underwent HBA and pacemaker implantation (HBA-PI) to control ventricular rate. Echocardiography was performed 1 year before HBA-PI, and up to 7 +/- 2 years of follow-up was conducted. An inverse linear relation was found between the relative increase of left ventricular (LV) end-diastolic diameter (EDD) during long-term RV pacing and LVEDD before HBA-PI (r = -0.61, p<0.001). Patients were divided into 2 groups: those with LVEDDs smaller than the mean LVEDD of 50 mm (group I, 46 +/- 2 mm, n = 28) and those with LVEDDs >50 mm (group II, 56 +/- 4 mm, n = 17). Before HBA-PI, patients in group I had significantly smaller LV weights (167 +/- 44 vs 238 +/- 56 g) and LV end-systolic diameters (30 +/- 2 vs 42 +/- 7 mm) and higher LV ejection fractions (64 +/- 5% vs 49+/- 12%) than those in group II. In group I, long-term RV pacing increased LVEDD, LV end-systolic diameter, LV weight, and left atrial diameter; increased mitral regurgitation; and decreased the LV ejection fraction and LV fractional shortening. No significant changes were observed during long-term RV pacing in group II. In conclusion, long-term RV pacing after HBA adversely affects LV structure and function in patients with initially normal LV dimensions and function.

Arrhythmias, Cardiac↗
PubMed2006

Electrocardiographic changes predicting sudden death in propofol-related infusion syndrome.

BACKGROUND: The occurrence of metabolic acidosis, rhabdomyolysis, hyperkalemia, and sudden cardiac death after long-term, high-dose propofol infusion has been referred to as propofol infusion syndrome (PRIS). OBJECTIVES: The purpose of this study was to explore the ECG abnormalities observed in a patient with PRIS in order to identify possible pathophysiologic mechanisms of the syndrome. METHODS: ECG changes in the index case were characterized by down-sloping ST-segment elevation in precordial leads V1 to V3 (Brugada-like ECG pattern). We subsequently assessed the relationship between this ECG pattern and the propofol infusion rate, the development of arrhythmias, and the occurrence of sudden death in a previously described cohort of 67 head-injured patients, seven of whom had been identified as having PRIS. RESULTS: Six of the PRIS patients developed the ECG pattern of ST-segment elevation in leads V1 to V3 and died within hours of irrecoverable electrical storm. This ECG pattern was the first aberration recorded hours before the death of these patients. ECGs that were available for 30 of 60 unaffected patients exhibited a normal pattern. None of the 60 patients developed ventricular arrhythmias. CONCLUSION: Our findings indicate that development of an acquired Brugada-like ECG pattern in severely head-injured patients is a sign of cardiac electrical instability that predicts imminent cardiac death. Future studies will determine whether such an ECG pattern also predicts imminent cardiac arrhythmia in other patient populations.

Acidosis↗
PubMed2005

Tailoring cardiac resynchronization therapy using interventricular asynchrony. Validation of a simple model.

This study explores the use of interventricular asynchrony (interVA) for optimizing cardiac resynchronization therapy (CRT), an idea emerging from a simple pathway model of conduction in the ventricles. Measurements were performed in six dogs with chronic left bundle branch block (LBBB) and in 29 patients of the Pacing Therapies for Congestive Heart Failure (PATH-CHF)-I study. In the dogs, intraventricular asynchrony (intraVA) was determined using left ventricular (LV) endocardial activation maps. In dogs and patients, the maximum rate of rise of LV pressure (LV dP/dt(max)) and the pulse pressure (PP) and interVA [time delay between upslope of LV and right ventricular (RV) pressure curves] were measured during LV, RV, and biventricular (BiV) pacing with various atrioventricular (AV) delays. Measurements in the canine hearts supported the pathway model in that optimal resynchronization occurred at approximately 50% reduction of intraVA and at an interVA value halfway that during LBBB and LV pacing. In patients with significant hemodynamic response during pacing (n = 22), intrinsic interVA and interVA at peak improvement (interVA(p)) varied widely between patients (from -83 to -15 ms and from -42 to +31 ms, respectively). However, the model predicted individual interVA(p) accurately (SD of +/-6 ms and +/-12 ms for LV dP/dt(max) and PP, respectively). At equal interVA, LV and BiV pacing produced equal hemodynamic response, but in 11 of 22 responders, BiV pacing reduced interVA insufficiently to reach the maximum hemodynamic response. LV pacing at short AV delay proved to result in better hemodynamics than predicted by the model, indicating that additional factors determine hemodynamics during LV preexcitation. Guided by a simple pathway model, interVA measurements accurately predict optimal hemodynamic performance in individual CRT patients.

Animals↗
PubMed2004

Left bundle branch block induces ventricular remodelling and functional septal hypoperfusion.

AIMS: Left ventricular (LV) dilatation, hypertrophy, and septal perfusion defects are frequently observed in patients with left bundle branch block (LBBB). We investigated whether isolated LBBB causes these abnormalities. METHODS AND RESULTS: In eight dogs, LBBB was induced by radio frequency ablation. Two-dimensional echocardiography showed that 16 weeks of LBBB decreased LV ejection fraction (by 23+/-14%) and increased LV cavity volume (by 25+/-19%) and wall mass (by 17+/-16%). The LV septal-to-lateral wall mass ratio decreased by 6+/-9%, indicating asymmetric hypertrophy. After onset of LBBB, myocardial blood flow (MBF, fluorescent microspheres) and systolic circumferential shortening [CS(sys), magnetic resonance (MR) tagging] decreased in the septum to 83+/-16% and -11+/-20% of baseline, respectively, and increased in LV lateral wall to 118+/-12% and 180+/-90% of baseline, respectively. MBF and CS(sys) values did not change over 16 weeks of LBBB. Changes in external mechanical work paralleled those in CS(sys). Glycogen content was not significantly different between septum and LV lateral wall of LBBB hearts (16 weeks) and control samples, indicating absence of hibernation. CONCLUSIONS: The asynchronous ventricular activation during LBBB leads to redistribution of circumferential shortening and myocardial blood flow and, in the long run, LV remodelling. Septal hypoperfusion during LBBB appears to be primarily determined by reduced septal workload.

Animals↗
PubMed2003

Intra-ventricular resynchronization for optimal left ventricular function during pacing in experimental left bundle branch block.

OBJECTIVES: We sought to investigate to what extent intra-ventricular asynchrony (intraVA) and inter-ventricular asynchrony (interVA) determine left ventricular (LV) function in canine hearts with left bundle branch block (LBBB) during ventricular pacing. BACKGROUND: Pacing therapy improves LV pump function in patients with heart failure and abnormal ventricular conduction supposedly due to resynchronization. However, the relationship between LV pump function and measures of asynchrony is not well established. METHODS: In 15 experiments, LV (various sites) and biventricular (BiV) pacing was performed at atrioventricular (AV) delays of 20 to 140 ms. Measured were the maximum rate of increase (dP/dt(max)) of LV pressure and LV stroke work (SW) (conductance catheter), interVA (time delay between the upslope of LV and RV pressures), and intraVA (from endocardial electrical activation maps). RESULTS: Induction of LBBB increased interVA (-6.4 +/- 8.6 to -28.4 +/- 8.5 ms [RV earlier]) and intraVA (4.9 +/- 2.4 to 18.0 +/- 3.3 ms), whereas LV dP/dt(max) and SW decreased (-13 +/- 18% and -39 +/- 24%, respectively). During LBBB, LV and BiV pacing increased LV dP/dt(max) and SW (mean increases 14% to 21% and 11% to 15%, respectively) without changing diastolic function or preload. Optimal improvement in LV function was obtained consistently when intraVA returned to pre-LBBB values, while interVA remained elevated. Normalization of intraVA required AV delays shorter than the baseline PQ time during LV apex and BiV pacing, thus excluding endogenous LV activation, but AV delays virtually equal to the baseline PQ time (difference 4 +/- 9 ms, p = NS) during pacing at (mid)lateral LV sites to obtain fusion between pacing-induced and endogenous activation. CONCLUSIONS: In LBBB hearts, optimal restoration of LV systolic function by pacing requires intra-ventricular resynchronization. The optimal AV delay to achieve this depends on both the site of pacing and baseline PQ time.

Animals↗
PubMed2003

Absence of reverse electrical remodeling during regression of volume overload hypertrophy in canine ventricles.

OBJECTIVE: Ventricular hypertrophy predisposes for cardiac arrhythmias, presumably due to prolongation of repolarization (electrical remodeling). The temporal relation between the development of hypertrophy and electrical remodeling, as well as their reversibility upon restoration of normal load, however, are poorly understood. This was investigated in the present study using volume overload hypertrophy induced by atrio-ventricular (AV) block and normalization of load by pacing. METHODS: Dogs were subjected to either 16 weeks of AV-block (CAVB group, n=9) or 8 weeks of AV-block followed by 8 weeks of right ventricular (RV) pacing at physiological heart rate (CAVB+PACE group, n=9). RESULTS: Left ventricular (LV) mass (2D-echocardiography) increased after 8 weeks of AV-block to approximately 30% above baseline and returned to 10+/-14% after 8 weeks of pacing. QT-time (surface ECG) also increased after AV-block. However, 8 weeks of pacing did not decrease QT and QTc-time (c=corrected for heart rate), neither during physiological pacing nor during temporary pacing at 100 beats/min. Lack of reverse electrical remodeling was confirmed by the absence of changes in LV and RV action potential duration (monophasic action potentials) at week 8 and 16. CONCLUSIONS: In volume overload hypertrophy due to AV-block, structural and electrical remodeling develop in parallel but restoration of physiological heart rate causes dissociation between reverse structural remodeling and reverse electrical remodeling.

Action Potentials↗
PubMed2003

Relation between abnormal ventricular impulse conduction and heart failure.

Ventricular pacing and left bundle branch block (LBBB) are two of the most common causes of asynchronous electrical activation of the ventricles. The sequence of activation is an important determinant of cardiac pump function. The sequence of activation during LBBB and during pacing at the conventional pacing site, the RV apex, is similar. In this article the literature on the effect of RV pacing and LBBB on regional and global LV pump function, on long-term adaptations (remodeling) and on their possible contribution to the development of heart failure is discussed. Evidence is increasing that asynchronous electrical activation contributes significantly to the development of heart failure.

Animals↗
PubMed2002

Quantification of interventricular asynchrony during LBBB and ventricular pacing.

The quantification of mechanical interventricular asynchrony (IVA) was investigated. In 12 dogs left bundle branch block (LBBB) was induced by radio frequency ablation. Left ventricular (LV) and right ventricular (RV) pressures were recorded before and after induction of LBBB and during LBBB + LV apex pacing at different atrioventricular (AV) delays. Four IVA measures were validated using computer simulations on experimentally obtained pressure signals. The most robust measure for IVA was the time delay between the upslope of the LV and RV pressure signals (DeltaT(up)), estimated by cross correlation. The induction of experimental LBBB decreased DeltaT(up) from -6.9 +/- 7.0 ms (RV before LV) to -33.9 +/- 7.6 ms (P < 0.05) in combination with a significant decrease of LV maximal first derivative of pressure development over time (dP/dt(max)). During LV apex pacing, DeltaT(up) increased with decreasing AV delay up to +20.9 +/- 14.6 ms (P < 0.05). Interventricular resynchronization (DeltaT(up) = 0 ms) significantly improved LV dP/dt(max) by 15.1 +/- 5.9%. QRS duration increased significantly after induction of LBBB but did not change during LV apex pacing. In conclusion, DeltaT(up) is a reliable measure of mechanical IVA, which adds valuable information concerning the nature of asynchronous activation of the ventricles.

Animals↗