Impact of cardiac resynchronization therapy using hemodynamically optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances.

OBJECTIVES: We sought to investigate the impact of six months of cardiac resynchronization therapy (CRT) on echocardiographic variables of left ventricular (LV) function. BACKGROUND: Cardiac resynchronization therapy has recently been introduced as a new therapeutic modality in patients with advanced heart failure (HF) and conduction abnormalities. However, most studies have only investigated the early hemodynamic effects of CRT. METHODS: Twenty-five patients (12 women and 13 men; 59.8 +/- 5.1 years old) with advanced HF caused by ischemic (n = 7) or idiopathic dilated cardiomyopathy (n = 18) and a prolonged QRS complex were analyzed. All patients underwent early hemodynamic testing with a randomized testing protocol; echocardiographic measurements were compared before implantation and after six months of CRT. RESULTS: Left ventricular end-diastolic and end-systolic diameters (LVEDD and LVESD, respectively) were significantly reduced after six months (LVEDD from 71 +/- 10 to 68 +/- 11 mm, p = 0.027; LVESD from 63 +/- 11 to 58 +/- 11 mm, p = 0.007), as were LV end-diastolic and end-systolic volumes (LVEDV from 253 +/- 83 to 227 +/- 112 ml, p = 0.017; LVESV from 202 +/- 79 to 174 +/- 101 ml, p = 0.009). Ejection fraction was significantly increased (from 22 +/- 7% to 26 +/- 9%, p = 0.03). "Nonresponders," with regard to LV volume reduction, had significantly higher baseline LVEDV, compared with "responders" (351 +/- 52 vs. 234 +/- 74 ml, p = 0.018). Overall, there was only mild mitral regurgitation at baseline, with a minor reduction by semiquantitative analysis. The results of early hemodynamic testing did not predict the volume response. CONCLUSIONS: Cardiac resynchronization therapy may lead to a reduction in LV volumes in patients with advanced HF and conduction disturbances. Volume nonresponders have significantly higher baseline LVEDV.

Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. The Pacing Therapies for Congestive Heart Failure Study Group. The Guidant Congestive Heart Failure Research Group.

BACKGROUND: Previous studies of pacing therapy for dilated congestive heart failure (CHF) have not established the relative importance of pacing site, AV delay, and patient heterogeneity on outcome. These variables were compared by a novel technique that evaluated immediate changes in hemodynamic function during brief periods of atrial-synchronous ventricular pacing. METHODS AND RESULTS: Twenty-seven CHF patients with severe left ventricular (LV) systolic dysfunction and LV conduction disorder were implanted with endocardial pacing leads in the right atrium and right ventricle (RV) and an epicardial lead on the LV and instrumented with micromanometer catheters in the LV, aorta, and RV. Patients in normal sinus rhythm were stimulated in the RV, LV, or both ventricles simultaneously (BV) at preselected AV delays in a repeating 5-paced/15-nonpaced beat sequence. Maximum LV pressure derivative (LV+dP/dt) and aortic pulse pressure (PP) changed immediately at pacing onset, increasing at a patient-specific optimal AV delay in 20 patients with wide surface QRS (180+/-22 ms) and decreasing at short AV delays in 5 patients with narrower QRS (128+/-12 ms) (P<0.0001). Overall, BV and LV pacing increased LV+dP/dt and PP more than RV pacing (P<0.01), whereas LV pacing increased LV+dP/dt more than BV pacing (P<0.01). CONCLUSIONS: In this population, CHF patients with sufficiently wide surface QRS benefit from atrial-synchronous ventricular pacing, LV stimulation is required for maximum acute benefit, and the maximum benefit at any site occurs with a patient-specific AV delay.

Transvenous biventricular pacing for heart failure: can the obstacles be overcome?

Despite increasing evidence of hemodynamic benefit and long-term improvement in clinical status of congestive heart failure (CHF) patients with left ventricular and biventricular pacing, the risks and technical limitations of placing a permanent left ventricular pacing lead have prevented widespread clinical adoption of this therapy. Results of this and other recent investigations suggest it is necessary to target specific sites on the left ventricle to maximize hemodynamic benefit. However, limitations and variations of coronary vein anatomy, as well as patient safety, lead dislodgement, pacing thresholds, lead handling, and ease-of-use issues, present technical challenges for current transvenous permanent pacing lead designs. However, a new transvenous lead system based on an over-the-wire design appears to solve many of these problems and has proved feasible in acute clinical studies.

Effects of dobutamine on isovolumic and ejection phase indices of cardiac contractility in conscious healthy dogs.

The aim of this study was to determine cardiac contractility using indices derived from cardiac catheterisation in conscious healthy dogs during dobutamine infusion. Eight dogs were studied. An ECG was recorded together with left ventricular pressure and volume which were measured using a conductance catheter with an integrated microtip pressure sensor. Eight indices of left ventricular systolic performance were derived from these records. Measurements were realised under basal conditions and during an incremental dobutamine challenge. The maximal rate of rise in ventricular pressure (max dP/dt), max dP/dt divided by the developed pressure and the mean systolic ejection rate were the most sensitive indices to detect dobutamine induced changes in contractility with maximal percentage changes of 122+/-11 per cent, 130+/-7 per cent and 102+/-24 per cent respectively. Ejection fraction increased significantly during dobutamine infusion (maximal percentage change of 43+/-9 per cent) whereas the pre-ejection period (PEP) and the left ventricular ejection time (LVET) decreased significantly (maximal percentage change of -41+/-2 per cent and -28+/-3 per cent respectively). All these six indices were significantly correlated with each other. Conversely, the ratio PEP/LVET and the LVET corrected for heart rate dependency showed a maximal percentage change of only -10+/-1 per cent and -16+/-7 per cent, respectively, during the dobutamine infusion and were not significantly correlated with the other contractility indices. This study demonstrated the feasibility of the conductance method to determine cardiac contractility in conscious healthy dogs submitted to a pharmacological stress testing and provides control values for eight indices of left ventricular contractility during dobutamine infusion at increasing dosages.

Modelling the arterial wall by finite elements.

The mechanical behaviour of the arterial wall was determined theoretically utilizing some parameters of blood flow measured in vivo. Continuous experimental measurements of pressure and diameter were recorded in anesthetized dogs on the thoracic ascending and midabdominal aorta. The pressure was measured by using a catheter, and the diameter firstly, at the same site, by a plethysmograph with mercury gauge and secondly, by a sonomicrometer with ferroelectric ceramic transducers. The unstressed radius and thickness were measured at the end of each experiment in situ. Considering that the viscous component is not important relatively to the nonlinear component of the elasticity and utilizing several equations for Young modulus calculation (thick and thin wall circular cylindrical tube formulas and Bergel's equation) the following values were obtained for this parameter: 0.6 MPa-2 MPa in midabdominal aorta and 2 MPa-6.5 MPa in thoracic ascending aorta. The behaviour of the aorta wall was modelled considering an elastic law and using the finite element program "Lagamine" working in large deformations. The discretized equilibrium equations are non-linear and a unique axi-symmetric, iso-parametric element of 1 cm in length with 8 knots was used for this bi-dimensional problem. The theoretical estimation of radius vessel, utilizing a constant 5 MPa Young modulus and also a variable one, are in good agreement with the experimental results, showing that this finite element model can be applied to study mechanical properties of the arteries in physiological and pathological conditions.

Isolation of the physiological regulation component of the arterial pressure time variation after postural stresses in by a model of the gravitational and arterial kinking effects.

Prompt active postural manoeuvres induce an immediate arterial pressure variation followed by a period of regulation. For the squatting manoeuvre, initial hypertension was explained by a rise of cardiac filling pressure due to "squeezing blood out of the veins of the legs", leading to an increase in stroke output by Frank-Starling mechanism. For a minor part, it was also explained by "kinking" of the femoral arteries. O'Donnel and Mc Ilroy observed an increase in central blood volume and accepted the idea of a rise of cardiac filling. However, they did not observe so consistent circulatory variations when postural changes were realized in a water tank. Therefore, they concluded that kinking of the arteries and veins of the legs could not be very important. Moreover, the immediate pressure variations, most often appearing in the first beat succeeding the postural manoeuvres cannot be easily explained by the previously invoked modifications of cardiac filling pressures. When Hoffman et al lifted dogs until they stood erect, the right ventricular stroke volume usually fell in the first beat after the postural change, but the left ventricular stroke volume did not fall for another 1-3 beats. When the dogs were rapidly lowered to standing on four legs again, a delay of 2-3 beats was also observed. Thus, another interpretation of immediate hypotension must be added. It should especially take into account the natural gravitational fluid mechanics phenomena imposed to the arterial blood. Besides, to allow the investigation of the orthostatic regulation of arterial blood pressure, it would be necessary to separate the cardiovascular regulation component of the arterial pressure time course from the pressure evolution that would naturally appear in the network without physiological contribution. It is the aim of this study.

Identification of three-element windkessel model: comparison of time and frequency domain techniques.

The problem of the parameter identification of the three-element windkessel model is studied. Minimization by least-square technique--LSQ--in time domain and frequential techniques--FFT--are compared. Continuous pressure and flow curves were recorded in the proximal aorta of an open chest dog. Comparison shows very high correlations between the parameter estimations obtained by LSQ and FFT methods. However, systematic differences appear between the calculated values, but do not seem to endanger physiological interpretation of the results.