Paced Heart Rate Research Articles

The Systolic Index: A Noninvasive Approach for the Assessment of Cardiac Function: Implications for Patients with DDD and CRT Devices

Our objective was to evaluate the systolic index (SI), the ratio between rate-corrected left ventricular ejection time (LVETc), and a preejection period surrogate (PEPsu), to assess cardiac function in patients with DDD and cardiac resynchronization therapy (CRT) pacemakers. LVETc and PEPsu were automatically measured from electrocardiogram and finger photoplethismography. Atrioventricular (AV) and mode switch (CRT to DDD) were used as hemodynamic challenges. Performance of SI, beat-by-beat systolic blood pressure (SBP), and Doppler aortic velocity/time integral (AoVTI) were compared in 36 patients, and SI's detection of CRT to DDD mode switch in nine patients, responders to CRT. AVs were changed from 30 ms to 250 ms (20 ms steps) at constant paced heart rate, alternating with a reference AV (RefAV), to reduce hemodynamic drift. The coefficient of variation (standard deviation/mean) of SI, SBP, and AoVTI during all RefAVs were used as error marker. The percentage detection of hemodynamic changes during AV transitions was a marker of sensitivity. Fifty-five patients (males 62%, age 69.6 ± 17) were studied. SI detected 441 of 544 transitions (81%) versus 361 (66%) of SBP (P = 0.005). Error during RefAVs was smaller for SI (3.4%) as compared to AoVTI (7.8%, P = 0.015) and to SBP (5.7%, P = 0.005). SIs correlated with AoVTI (R from 0.71 to 0.98, all P < 0.001). SI detected all CRT to DDD changes (P < 0.001). The noninvasive SI obtained with a simple, observer-independent hemodynamic assessment procedure has higher accuracy than SBP and AoVTI and better sensitivity than SBP. It detects mechanical resynchronization in CRT and allows programming a suitable AV delay.

Haemodynamic effects of different basic heart rates in ambulatory heart failure patients treated with cardiac resynchronization therapy

The impact of different basic paced heart rates (pHRs) in patients receiving cardiac resynchronization therapy (CRT) remains largely unknown. The aim of the present study was to investigate the haemodynamic effects of different pHRs (60 or 80 b.p.m.), using an implanted haemodynamic monitor (IHM), during a 2-week period in ambulatory CRT patients. Ten CRT patients received an IHM (Chronicle(®), Medtronic Inc.) to continuously record right ventricular systolic (RVSP) and diastolic (RVDP) pressure, as well as estimated pulmonary artery diastolic pressure (ePAD) during a 2-week period at two basic pHR programming (60 and 80 b.p.m.). Cardiac output (CO) was calculated using a validated IHM algorithm. At the end of each period, 6 min walk test (6MWT), quality of life (QoL), and plasma levels of brain natriuretic peptide (BNP) were also assessed. Pacing at 80 b.p.m. significantly reduced the 2-week average of ePAD compared with 60 b.p.m. (23.4 ± 6.2 vs. 25.1 ± 6.5 mmHg, P = 0.03), whereas CO was increased (4.5 ± 1.3 vs. 4.2 ± 1.4 L/min; P = 0.01). Similarly ePAD, RVSP, and RVDP were significantly lower with a pHR of 80 b.p.m. (P < 0.05). The 6MWT, QoL score, and BNP were not affected by the pHR. In CRT patients, a basic pHR of 80 b.p.m. compared with 60 b.p.m. reduces filling pressures and increases CO during a 2-week period of ambulatory living. This suggests that increasing the basic pHR may be considered to achieve short-term haemodynamic improvement. The long-term effects of differential pHR programming remain to be established.

Cardiac ryanodine receptors control heart rate and rhythmicity in adult mice

The molecular mechanisms controlling heart function and rhythmicity are incompletely understood. While it is widely accepted that the type 2 ryanodine receptor (Ryr2) is the major Ca(2+) release channel in excitation-contraction coupling, the role of these channels in setting a consistent beating rate remains controversial. Gain-of-function RYR2 mutations in humans and genetically engineered mouse models are known to cause Ca(2+) leak, arrhythmias, and sudden cardiac death. Embryonic stem-cell derived cardiomyocytes lacking Ryr2 display slower beating rates, but no supporting in vivo evidence has been presented. The aim of the present study was to test the hypothesis that RYR2 loss-of-function would reduce heart rate and rhythmicity in vivo. We generated inducible, tissue-specific Ryr2 knockout mice with acute ∼50% loss of RYR2 protein in the heart but not in other tissues. Echocardiography, working heart perfusion, and in vivo ECG telemetry demonstrated that deletion of Ryr2 was sufficient to cause bradycardia and arrhythmia. Our results also show that cardiac Ryr2 knockout mice exhibit functional and structural hallmarks of heart failure, including sudden cardiac death. These results illustrate that the RYR2 channel plays an essential role in pacing heart rate. Moreover, we find that RYR2 loss-of-function can lead to fatal arrhythmias typically associated with gain-of-function mutations. Given that RYR2 levels can be reduced in pathological conditions, including heart failure and diabetic cardiomyopathy, we predict that RYR2 loss contributes to disease-associated bradycardia, arrhythmia, and sudden death.

Fully Automatable, Reproducible, Noninvasive Simple Plethysmographic Optimization: Proof of Concept and Potential for Implantability

Hemodynamic optimization of cardiac resynchronization therapy (CRT) can be achieved reproducibly and--with bulky, nonimplantable equipment--noninvasively. We explored whether a simple photoplethysmogram signal might be used instead. Twenty patients (age 65 ± 12) with CRT underwent automatic atrioventricular (AV) delay optimization, using a multiple-transitions protocol, at two atrially paced heart rates: just above sinus rate ("slow ApVp," 77 ± 11 beats per minute [bpm]) and 100 bpm ("fast ApVp"). We then retested to assess short-term reproducibility. All 80 optimizations identified an optimum (correctly oriented parabola). At 100 bpm, the simple photoplethysmogram had wider scatter between repeat optimizations than did Finometer: standard deviation of difference (SDD) 22 ms versus 14 ms, respectively, P = 0.028. The simple photoplethysmogram improved in reproducibility when slope (instead of peak) of its signal was used for optimization, becoming as reproducible as Finometer (SDD 14 ms vs 14 ms, P = 0.50). At slow heart rate, reproducibility of simple photoplethysmogram-based optimization worsened from 14 to 22 ms (P = 0.028), and Finometer-based optimization from 14 to 26 ms (P = 0.005). Increasing the number of replicates averaged improved reproducibility. For example, SDD of simple photoplethysmogram optimization (using peak) fell from 62 ms with two replicates to 22 ms with eight replicates (P < 0.0001). At 100 bpm, the eight-replicate protocol takes ∼12 minutes. A 12-minute protocol of simple photoplethysmographic AV optimization can be processed fully automatically. Blinded test-retest reproducibility of the optimum AV is good and improves with more replicates. If benefits to some patients are not to be neutralized by harm to others, endpoint studies should first test check narrowness of "within-patient error bars."

007 Should current modalities of VV optimisation be trusted? An assessment of the internal validity of echocardiographic, electrocardiographic and haemodynamic modalities of optimisation: Abstract 007 Figure 1

Background In atrial fibrillation (AF), VV optimisation of biventricular pacemakers can be examined in isolation. We used this approach to evaluate the internal validity of three VV optimisation methods. Methods 20 patients (16 men, age 75±7) in AF were optimised, at two paced heart rates, by LVOT VTI (flow), non-invasive arterial pressure, and ECG (minimising QRS duration). Each optimisation method was evaluated by: singularity (unique peak of function), reproducibility of optimum, and biological plausibility of the distribution of optima. Results The reproducibility (SD of the difference, SDD) of the optimal VV delay is 10 ms for pressure, vs 8 ms (p=NS) for QRS and 34 ms (p 2 =10.9, p Conclusions Using non-invasive arterial pressure, VV delay optimisation is achievable with good precision, satisfying all 3 criteria of internal validity, and the optimum is unaffected by heart rate. Neither QRS minimisation nor LVOT VTI satisfy all validity criteria and are therefore weaker candidate modalities for VV optimisation.

A systematic approach to designing reliable VV optimization methodology: Assessment of internal validity of echocardiographic, electrocardiographic and haemodynamic optimization of cardiac resynchronization therapy

BackgroundIn atrial fibrillation (AF), VV optimization of biventricular pacemakers can be examined in isolation. We used this approach to evaluate internal validity of three VV optimization methods by three criteria. Methods and resultsTwenty patients (16 men, age 75±7) in AF were optimized, at two paced heart rates, by LVOT VTI (flow), non-invasive arterial pressure, and ECG (minimizing QRS duration). Each optimization method was evaluated for: singularity (unique peak of function), reproducibility of optimum, and biological plausibility of the distribution of optima.The reproducibility (standard deviation of the difference, SDD) of the optimal VV delay was 10ms for pressure, versus 8ms (p=ns) for QRS and 34ms (p<0.01) for flow.Singularity of optimum was 85% for pressure, 63% for ECG and 45% for flow (Chi2=10.9, p<0.005).The distribution of pressure optima was biologically plausible, with 80% LV pre-excited (p=0.007). The distributions of ECG (55% LV pre-excitation) and flow (45% LV pre-excitation) optima were no different to random (p=ns).The pressure-derived optimal VV delay is unaffected by the paced rate: SDD between slow and fast heart rate is 9ms, no different from the reproducibility SDD at both heart rates. ConclusionsUsing non-invasive arterial pressure, VV delay optimization by parabolic fitting is achievable with good precision, satisfying all 3 criteria of internal validity. VV optimum is unaffected by heart rate. Neither QRS minimization nor LVOT VTI satisfy all validity criteria, and therefore seem weaker candidate modalities for VV optimization. AF, unlinking interventricular from atrioventricular delay, uniquely exposes resynchronization concepts to experimental scrutiny.

Shortening of atrioventricular delay at increased atrial paced heart rates improves diastolic filling and functional class in patients with biventricular pacing

BackgroundUse of rate adaptive atrioventricular (AV) delay remains controversial in patients with biventricular (Biv) pacing. We hypothesized that a shortened AV delay would provide optimal diastolic filling by allowing separation of early and late diastolic filling at increased heart rate (HR) in these patients.Methods34 patients (75 ± 11 yrs, 24 M, LVEF 34 ± 12%) with Biv and atrial pacing had optimal AV delay determined at baseline HR by Doppler echocardiography. Atrial pacing rate was then increased in 10 bpm increments to a maximum of 90 bpm. At each atrial pacing HR, optimal AV delay was determined by changing AV delay until best E and A wave separation was seen on mitral inflow pulsed wave (PW) Doppler (defined as increased atrial duration from baseline or prior pacemaker setting with minimal atrial truncation). Left ventricular (LV) systolic ejection time and velocity time integral (VTI) at fixed and optimal AV delay was also tested in 13 patients. Rate adaptive AV delay was then programmed according to the optimal AV delay at the highest HR tested and patients were followed for 1 month to assess change in NYHA class and Quality of Life Score as assessed by Minnesota Living with Heart Failure Questionnaire.Results81 AV delays were evaluated at different atrial pacing rates. Optimal AV delay decreased as atrial paced HR increased (201 ms at 60 bpm, 187 ms at 70 bpm, 146 ms at 80 bpm and 123 ms at 90 bpm (ANOVA F-statistic = 15, p = 0.0010). Diastolic filling time (P < 0.001 vs. fixed AV delay), mitral inflow VTI (p < 0.05 vs fixed AV delay) and systolic ejection time (p < 0.02 vs. fixed AV delay) improved by 14%, 5% and 4% respectively at optimal versus fixed AV delay at the same HR. NYHA improved from 2.6 ± 0.7 at baseline to 1.7 ± 0.8 (p < 0.01) 1 month post optimization. Physical component of Quality of Life Score improved from 32 ± 17 at baseline to 25 ± 12 (p < 0.05) at follow up.ConclusionsIncreased heart rate by atrial pacing in patients with Biv pacing causes compromise in diastolic filling time which can be improved by AV delay shortening. Aggressive AV delay shortening was required at heart rates in physiologic range to achieve optimal diastolic filling and was associated with an increase in LV ejection time during optimization. Functional class improved at 1 month post optimization using aggressive AV delay shortening algorithm derived from echo-guidance at the time of Biv pacemaker optimization.

Higher rates to reduce irregularity: the use of overdrive pacing in atrial fibrillation

For a long time, it was a matter of debate whether fast rate or ventricular irregularity during atrial fibrillation (AF) was primarily responsible for the perception of palpitations, development of cardiomyopathy, and system emboli from the fibrillating atria. Recent studies have shown that ventricular irregularity associated with AF and manifested by random QRS intervals that constitute the diagnostic clue in scalar electrocardiography, can elicit symptoms and cardiomyopathy regardless of the rate. 1,2 Reduction of ventricular irregularity in AF patients in addition to control of fast ventricular rates, therefore, appears sensible to reduce symptoms and minimize the risk of cardiomyopathy. The underlying mechanisms of ventricular irregularity are uncertain and include concealed conduction within the atrioventricular (AV) node secondary to decremental conduction or electrical modulation of AV nodal propagation or pacemaker activity in the AV node. 1 If rate control is preferred to rhythm control, suppression of AV conduction with pharmacologic treatment and ablation of the AV junction are nowadays the established methods according to guidelines. However, the side effects and non-compliance associated with drug treatment or pacemaker dependency after ablation with potentially unfavourable effects of long-term right ventricular apical pacing often undermine the effectiveness of these therapies. These disadvantages urge the search for other therapeutic modalities for a safe and easy reduction of ventricular irregularity in AF. In 1983, Wittkampf and De Jongste 3 showed that continuous pacing in the right ventricle reduced the irregularity of QRS intervals during AF; faster pacing rates produced even more regularity by elimination of a large proportion of longer QRS intervals observed during slower ventricular rates. This phenomenon of rate stabilization is attributed to suppression or delay in AV nodal conduction by retrograde penetration of ventricular stimuli. This concept was incorporated in rate smoothing pacing algorithms that indeed significantly reduced variability of successive QRS intervals in AF patients. Unfortunately, the application of this algorithm was associated with a concomitant increase in mean heart rate by 21‐29%. 3 This drawback limited the widespread use of rate smoothing algorithms in paced patients with paroxysmal or permanent AF. In 1997, we tested a new rate smoothing programme delivered by the former Vitatron company, that uses a dynamic average of successive sensed or paced heart rates as a reference point. 4 The pacing rate followed the average heart rate and started pacing when the average ventricular rate dropped by 2.5 bpm. In addition, the algorithm prevented the occurrence of sudden brady- or tachyarrhythmia by pacing at a decelerating or accelerating rate at 2 bpm. In the acute pacing study, we observed that variability of the RR intervals could be reduced by 73% while the heart rate during pacing did not increase significantly (2%) compared with the preceding period without pacing. 5 In the unpublished randomized, single-blinded cross-over trial of patients with permanent (n ¼ 91) and paroxysmal AF (n ¼ 93), we observed a significant reduction in the variance of RR intervals in both patients categories. 6 However, quality of life, measured

Lowering Of Heart Rate After Exercise Training Is Associated With Adaptations In Skeletal Muscle: Insight From Heart Rate Pacing During Trained And Untrained Muscle Exercise

Lowering Of Heart Rate After Exercise Training Is Associated With Adaptations In Skeletal Muscle: Insight From Heart Rate Pacing During Trained And Untrained Muscle Exercise

Transient repolarization instability following the initiation of cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) may cause changes in ventricular repolarization (VR), particularly in the initial phase of treatment. This study investigated the effect of CRT cessation and re-initiation on parameters of VR duration and heterogeneity at different paced heart rates. Cardiac resynchronization therapy was inactivated for 2 weeks in 16 treatment responders to CRT. QT and JT intervals were measured on the surface electrocardiogram at 60, 70, and 80 bpm (randomized order) and vectorcardiography (VCG) was performed with CRT 'on' (day 0), 'off' (day 0, 1, 7, and 14) and after CRT re-initiation (day 14, 15, 16, and 21). On day 0 ('on') and 14 ('off') echocardiography, the 6 min walking distance and brain natriuretic peptide were assessed. The QT interval at baseline (CRT 'on'), measured at 60, 70, and 80 bpm, was 482 ± 31, 468 ± 37, and 457 ± 39 ms, respectively, and decreased by 5, 5, and 6% during the first week following CRT cessation (all P< 0.05). Immediately after re-initiation on day 14, it increased again by 20 ± 18 (4%; P< 0.05), 34 ± 39 (8%; P< 0.01), and 16 ± 38 ms (4%, ns) followed by a gradual decrease towards previous 'off' levels. Similar changes were observed for the JT interval. Ventricular repolarization duration was significantly shortened by increasing the paced heart rate from 60 to 70 and 80 bpm. Vectorcardiography parameters reflecting VR gradients (ST-vector magnitude, Tarea, and Tavplan) increased significantly (by 31, 45, and 71%) after CRT cessation. A similar but non-significant pattern was observed after CRT re-initiation. The increase in repolarization duration and gradients observed after CRT initiation suggests a transient state of VR instability that can be attenuated by programming of higher paced heart rates during the initial phase of treatment.

Interatrial Conduction Correlates with Optimal Atrioventricular Timing in Cardiac Resynchronization Therapy Devices

Echocardiographic optimization of the atrioventricular delay (AV) may result in improvement in cardiac resynchronization therapy (CRT) outcome. Optimal AV has been shown to correlate with interatrial conduction time (IACT) during right atrial pacing. This study aimed to prospectively validate the correlation at different paced heart rates and examine it during sinus rhythm (Sinus). An electrophysiology catheter was placed in the coronary sinus (CS) during CRT implant (n = 33). IACT was measured during Sinus and atrial pacing at 5 beats per minute (bpm) and 20 bpm above the sinus rate as the interval from atrial sensing or pacing to the beginning of the left atrial activation in the CS electrogram. P-wave duration (PWd) was measured from 12-lead surface electrocardiogram, and the interval from the right atrial to intrinsic right ventricular activation (RA-RV) was measured from device electrograms. Within 3 weeks after the implant patients underwent echocardiographic optimization of the sensed and paced AVs by the mitral inflow method. Optimal sensed and paced AVs were 129 ± 19 ms and 175 ± 24 ms, respectively, and correlated with IACT during Sinus (R = 0.76, P < 0.0001) and atrial pacing (R = 0.75, P < 0.0001), respectively. They also moderately correlated with PWd (R = 0.60, P = 0.0003 during Sinus and R = 0.66, P < 0.0001 during atrial pacing) and RA-RV interval (R = 0.47, P = 0.009 during Sinus and R = 0.66, P < 0.0001 during atrial pacing). The electrical intervals were prolonged by the increased atrial pacing rate. IACT is a critical determinant of the optimal AV for CRT programming. Heart rate-dependent AV shortening may not be appropriate for CRT patients during atrial pacing.

Heart rates in cardiac resynchronization: the art of optimal device programming

This editorial refers to ‘Acute haemodynamic effects of increase in paced heart rate in heart failure patients recorded with an implantable haemodynamic monitor’ by M. Staahlberg et al. , doi:10.1093/europace/euq354. Cardiac resynchronization therapy (CRT) has become the standard therapy for patients with decreased systolic left ventricular (LV) function with the indication extending most recently also the less symptomatic patients.1 Implantation rates in Europe have steadily increased with a clear difference between countries.2 Objective response rates with significant reverse LV remodelling have remained at 50–70% depending on the definition. Reverse remodelling, however, is the pre-requisite for decreasing hard clinical endpoints.3 Optimal delivery of CRT rests on three legs: (i) patient selection, (ii) optimal implantation, and (iii) optimal device programming. Although the first and, to lesser extent, the second point have been extensively studied, optimal device programming remains obscure, mostly due to time-consuming procedures for optimization and complex interdependence of the several parameters.4 Randomized studies are scarce and evidence is only available for optimal atrioventricular (AV) intervals. Heart rates have become critical in heart failure patients with the goal to ‘go as low as possible’.5 If the heart rate per se needs to be low or if this is merely a surrogate for efficient suppression of neurohormonal activation remains controversial even though more data with the selective sinus node inhibitor ivabradine become available.5 Furthermore, it is unclear what optimal heart rates at exercise are. Chronotropic incompetence has been associated with adverse outcome in heart failure patients. …

Impaired Heart Rate Responses and Exercise Capacity in Heart Failure Patients With Paced Baseline Rhythms

Background Conduction system disease and beta-blocker therapy are both common among heart failure (HF) patients and contribute to increasing reliance on paced rhythms. We hypothesized that many HF patients dependent on pacing have suboptimal heart rate responses and associated limitations in exercise capacity. Methods and Results We studied 122 HF patients (left ventricular ejection fractions ≤40%) referred for cardiopulmonary exercise testing, comparing those with pacing at baseline with those with native rhythms. The paced group (PG) had lower resting (71 ± 9 vs 75 ± 15 beats/min; P = .048) and peak heart rates (103 ± 22 vs 127 ± 27 beats/min; P < .0001). Although beta-blockers were prescribed with similar frequency in both groups (90% vs 85%), average dose was higher in the PG. Inotropic reserve (oxygen pulse) was similar in both groups (11.1 ± 3.3 vs 11.1 ± 3.4 mL/beat; P = .94), consistent with equivalent stroke volumes, but chronotropic incompetence was higher (95% vs 71%, P = .001) and peak VO 2 was lower (12.2 ± 3.4 vs 14.2 ± 4.1 mL/kg/min; P = .004) in the PG. Conclusions Chronotropic incompetence and exercise capacity are worse in HF patients depending on paced heart rate responses. This has implications for quality of life as well as advanced therapy choices based on exercise capacity. Reevaluating beta-blocker dosing and optimizing pacemaker programming may therefore benefit the growing population of HF patients with device-dependent rhythms.

Ivabradine improves coronary flow reserve in patients with stable coronary artery disease

ObjectivesAlthough treatment with ivabradine reduces the incidence of hospital admissions for myocardial infarction and coronary revascularisation, there are no data concerning its effect on coronary circulation. The purpose of this study was to assess the effects of ivabradine on coronary flow velocity and flow reserve (CFR) in patients with stable coronary artery disease (CAD). MethodsDuring diagnostic coronary angiography (baseline), twenty-one patients with stable CAD underwent coronary flow velocity measurements (APVcm/s) in a non-culprit vessel, using a Doppler guidewire, at rest (r) and after adenosine administration to achieve maximal hyperaemia (h). During programmed coronary intervention in the culprit vessel, the same measurements were repeated one week after treatment with ivabradine (5mg twice daily), both at the intrinsic heart rate and at a paced heart rate identical to that before treatment. CFR was defined as h-APV/r-APV. ResultsHeart rate was significantly lower after treatment with ivabradine (78±14bpm vs 65±9bpm, p<0.001). Also, a reduction of r-APV (17.0±5.5 vs 19.7±7.6, p=0.003) and augmentation of h-APV (57.9±17.8 vs 53.5±21.4, p=0.009) leading to CFR improvement (3.51±0.81 vs 2.78±0.61, p<0.001) were observed. During pacing, although r-APV reverted to values similar to those before treatment (20.0±6.5 vs 19.7±7.6, p=NS), a sustained improvement in h-APV was observed (59.5±19.7 vs 53.5±21.4, p=0.007) and CFR remained higher than before treatment (3.04±0.66 vs 2.78±0.61, p<0.001). ConclusionsIvabradine treatment significantly improves hyperaemic coronary flow velocity and CFR in patients with stable CAD. These effects remain even after heart rate correction indicating improved microvascular function.

High‐Rate Pacing Reduces Variability of Repolarization and Prevents Repolarization‐Dependent Arrhythmias in Dogs With Chronic AV Block

high-rate pacing may have an inhibitory effect on the initiation of Torsade de Pointes arrhythmias (TdP). However, permanent pacing is only indicated in high-risk patients. We performed a proof of concept study into automatic overdrive pacing for prevention of drug-induced TdP, using short-term variability of repolarization (STV) as a feedback parameter of arrhythmic risk. the minimal signal sampling frequency required for measuring STV was determined through computer simulation. Arrhythmogenic response to dofetilide (25 microg/kg/5 minutes) was tested at two different paced heart rates (60-65 bpm vs 100-110 bpm) in 7 dogs with chronic atrioventricular block, while recording right and left ventricular (LV) monophasic action potential (MAP) and LV electrogram (EGM). Simulations showed a sampling frequency of 500 Hz is sufficient to capture relevant STV values. High-rate pacing prevented dofetilide-induced TdP seen at the low rate (low: 6/7 vs high: 1/7). At the low rate, STV from LV MAP duration increased before occurrence of spontaneous, ectopic activity and TdP (1.7 ± 0.6-3.0 ± 1.8 ms, P < 0.05), but at the high-rate STV did not change significantly (0.9 ± 0.2-1.5 ± 1.4 ms, NS). Regression analysis showed a close relation between STV calculated from LV MAP and from LV EGM (R(2) = 0.71). high-rate pacing increases repolarization reserve in dogs with chronic atrioventricular block, preventing dofetilide-induced TdP. Changes in repolarization reserve are reflected in values of STV.

Acute haemodynamic effects of increase in paced heart rate in heart failure patients recorded with an implantable haemodynamic monitor

The aim of this study was to investigate the acute effects of different biventricularly paced heart rates (pHRs) on right ventricular (RV) haemodynamics in heart failure (HF) patients with an implantable haemodynamic monitor (IHM). At rest, seven pHRs, range 60-120 bpm (steps of 10), were randomly programmed and maintained for 60 s in 10 patients (male, 65±12 years, New York Heart Association II-III). Right ventricular systolic (RVSP) and diastolic pressures, estimated pulmonary artery diastolic (ePAD) pressure, and RV+dP/dt were recorded beat-to-beat using the IHM. Cardiac output (CO) was estimated from the RV pressure waveforms and arterial blood pressure was measured (Portapres®). To compare the haemodynamic effects of increased pHR at rest to that of spontaneous, sinus-driven heart rate (HR) increase, patients also performed a symptom-limited bicycle exercise. At rest, RV+dP/dt increased significantly with elevated pHR (P, main effect, <0.001), whereas filling pressures (ePAD and RVSP) decreased significantly in the range 60-100 bpm (P<0.03 and P<0.003, respectively) but tended to increase or level out at pHRs>00 bpm. At a pHR of 100 bpm, ePAD was 1.4 mmHg lower compared with 60 bpm (P<0.01). Cardiac output increased gradually with elevated pHR at rest (P<0.001). Both total peripheral and estimated pulmonary arterial resistance significantly decreased with increased pHR. During exercise-induced maximum HR increase, RV+dP/dt, ePAD, and CO were all significantly higher compared with the corresponding pHR at rest. During cardiac resynchronization therapy in HF patients, the force frequency relationship is present in the RV, as increasing the pHR in the range 60-100 bpm results in decreased filling pressures and increased CO.

Response to Letter Regarding Article, “Role of Left Ventricular Stiffness in Heart Failure With Normal Ejection Fraction”

We would like to thank Dr Kass for his interest in our study, which investigated hemodynamic characteristics of patients with heart failure and normal ejection fraction (HFNEF).1 An important finding in our study was that with increased paced heart rates the patients in the HFNEF group showed a decrease in end-diastolic volume leading to reduced stroke volume, which limited their ability to increase cardiac output and may explain their exertional limitations. These results were in contrast to those in the control group where end-diastolic volumes and stroke …

Human, Bovine and Porcine Systematic Vascular Input Impedances Are Not Equivalent: Implications for Device Testing and Xenotransplantation in Heart Failure

Advanced therapies for heart failure (HF), such as mechanical circulatory support (MCS) devices and xenotransplantation, are usually tested in bovine and porcine models. This approach assumes a priori that animal (patho)physiology will closely match that of humans. Systemic aortic input impedance (Z(ART)) is an important physiologic determinant of left ventricular (LV) performance. We tested the hypothesis that Z(ART) is lower in bovine and porcine than in humans with normal or failing hearts. High-fidelity aortic pressure and flow waveforms were recorded intra-operatively at native and paced heart rates of 100 beats per minute (bpm) in adult human patients with normal LV function (n = 13) or end-stage HF (n = 15), and normal calves (n = 10) and pigs (n = 18). Fast Fourier transformation was used to calculate Z(ART), and arterial resistance and compliance were estimated using a 4-element Windkessel model. Humans with HF had greater Z(ART) than those with normal LV function, characterized by higher resistance (1.16 +/- 0.12 vs 1.00 +/- 0.10 mm Hg x s/ml, p < 0.05) and lower compliance (1.53 +/- 0.21 vs 1.88 +/- 0.33 ml x mm Hg, p < 0.05). Healthy calves and pigs had significantly lower resistance (calf: 0.63 +/- 0.07 mm Hg x s/ml; pig: 0.90 +/- 0.07 mm Hg x s/ml) and higher compliance (calf: 2.79 +/- 0.37 ml x mm Hg; pig: 2.80 +/- 0.64 ml x mm Hg) when compared to humans (p < 0.05) with normal or failing hearts. Z(ART) is significantly lower in calves and pigs than in humans with or without HF. This finding has important implications for the pre-clinical testing of MCS devices and xenotransplants, which are usually examined in bovine and porcine models, respectively. Specifically, these therapies may respond differently in humans than animals due to non-equivalence of systemic after-load.

Abstract 4310: Chronic Effects of Surgical Ventricular Restoration on Left Ventricular Function: 6 Months Follow-Up by Pressure-Volume Loops

Previous studies have demonstrated beneficial acute effects of surgical ventricular restoration (SVR) on mechanical dyssynchrony and left ventricular (LV) function, and improved mid- and long-term clinical parameters. However, chronic effects on systolic and diastolic LV function are still largely unknown. We studied 9 patients with ischemic dilated cardiomyopathy who underwent SVR. In all patients, invasive hemodynamic measurements by the conductance catheter (pressure-volume loops) were obtained during catheterization before and 6 months after surgery. In addition, NYHA classification, Minnesota Quality of Life (QoL)-score and 6-minute-hall-walk-test (6min-HWT) were assessed. At 6 months follow-up, all patients were alive and clinically significantly improved: NYHA class from 3.3±0.5 to 1.4±0.7, QoL-score from 46±22 to 15±15 and 6min-HWT from 302±123 to 444±78 m (all p&lt;0.01). Hemodynamic data at fixed paced heart rate (80 bpm), showed improved cardiac output (4.8±1.4 to 5.6±1.1 L/min) (p =0.09), stroke work (6.5±1.9 to 7.1±1.4 mmHg.L) (p =0.05) and LV ejection fraction (36±10 to 46±10%) (p &lt;0.001). LV surgical remodeling was sustained at 6 months: end-diastolic volume decreased from 246±70 to 180±48 mL and end-systolic volume from 173±77 to 103±40 mL (both p&lt;0.001). LV mechanical dyssynchrony decreased from 29±6 to 26 ±3% (p&lt;0.001) and ineffective internal LV flow fraction decreased from 58±30 to 42±18% (p&lt;0.005). Early relaxation (tau, −dP/dt MIN ) was unchanged, but diastolic stiffness constant (K ED ) increased from 0.012±0.003 to 0.023±0.007 mL −1 (p&lt;0.001) at 6 months follow-up. SVR leads to maintained LV volume reduction at 6 months follow-up. In addition, we observed improved systolic function and unchanged early diastolic function, but impaired passive diastolic properties. Clinical improvement, supported by decreased NYHA class, improved QoL-score and improved 6-min-HWT may be related to improved systolic function and reduced mechanical dyssynchrony.

Post-thoracentesis trapped lung

A 68-year-old man with a history of diabetes mellitus, advanced ischemic cardiomyopathy and and hemodialysis-dependent renal failure was admitted to the hospital with a one-week history of confusion and weakness. Six months prior to admission, he was noted to have a large left pleural effusion, for which he had refused further workup. The patient denied alcohol use. He smoked three cigarettes /day but had been a heavy smoker previously. On examination, he was afebrile, blood pressure was 85/48 mmHg, paced heart rate 60 beats/minute and respiratory rate 22 breaths/minute. Physical examination revealed decreased breath sounds and crackles over the left chest. Initial chest X-ray showed complete opacification of the left hemithorax and patchy infiltrates on the right lung base [Figure 1A]. Empiric treatment of sepsis was begun with broad spectrum antibiotics and crystalloid volume resuscitation. An ultrasound-guided thoracentesis yielded one liter of serous fluid with a pH of 7.2; total cell count of 450/mm 3, 60% neutrophils; total protein 3 g/dl; glucose 32 mg/dl and LDH 790U/L. Cultures grew pan-sensitive Streptococcus pneumoniae. Acid-fast bacilli, fungal stains and cytology of the pleural fluid were negative. Post-thoracentesis chest X-ray demonstrated a decrease in left pleural effusion and left anterior pneumothorax [Figure 1B]. A chest computed tomographic scan revealed a septated area of ex vacuo pneumothorax with collapsed lung and a left pleural effusion [Figure 2]. The patient refused to undergo thoracotomy with decortication and was treated.