Catherine Mumford

Electrical and mechanical components of dyssynchrony in heart failure patients with normal QRS duration and left bundle-branch block:impact of left and biventricular pacing

Background—Resynchronization pacing is an effective symptomatic treatment for heart failure patients with prolongation of the QRS duration (QRSd). Dyssynchronous contraction of the left ventricle is also observed with normal QRSd. We set out to determine how electrical activation of the left ventricular (LV) free wall differed between patients with left bundle-branch block (LBBB) and normal QRSd and if synchrony improved during pacing in patients with normal QRSd. Methods and Results—Twenty-two patients were implanted with resynchronization pacemakers, 13 with LBBB (mean QRS, 171 ms) and 9 with normal QRSd <120 ms (mean, 100 ms). LV lead electrograms and surface ECGs in sinus rhythm (unpaced) were recorded. Conventional and tissue Doppler echocardiography were performed without pacing, with LV and biventricular pacing at optimal atrioventricular delay. Lead electrograms from the LV free wall were later in the LBBB patients in absolute terms (155 ms [SD 23] versus 65.5 ms [SD 25]; P =0.05) and also relative to the surface QRS (90.5% [SD 8] versus 65.5% [SD 24]). Improved synchrony of the left and right ventricles (interventricular synchrony) and of the LV myocardial segments (intraventricular synchrony) was observed for patients with LBBB and normal QRSd. Baseline LV synchrony correlated with timing of LV free-wall electrical activation. Improved intraventricular synchrony during pacing also correlated with LV free-wall electrical activation time. Conclusions—Resynchronization of systole can be achieved for patients with normal QRSd and LBBB during biventricular and LV pacing. The timing of LV free-wall electrical activation correlated with the improvement in synchrony.

A new noninvasive measurement system for wave intensity : evaluation of carotid arterial wave intensity and reproducibility

Abstract. Wave intensity (WI) is a new hemodynamic index that provides information about the dynamic behavior of the heart and the vascular system and their interaction. Carotid arterial wave intensity in normal subjects has two positive peaks. The first peak, W1, occurs during early systole, the magnitude of which increases with increases in cardiac contractility. The second peak, W2, which occurs towards the end of ejection, is related to the ability of the left ventricle to actively stop aortic blood flow. Between the two positive peaks, a negative area, NA, is often observed, which signifies reflections from the cerebral circulation. The time interval between the R-wave of ECG and the first peak (R − W1) corresponds to the pre-ejection period, and that between the first and second peaks (W1 − W2) corresponds to ejection time. We developed a new ultrasonic on-line system for obtaining WI and arterial stiffness (β). The purpose of this study was (1) to report normal values of various indices derived from WI and β measured with this system, and (2) to evaluate the intraobserver and interobserver reproducibility of the measurements. The measurement system is composed of a computer, a WI unit, and an ultrasonic machine. The WI unit gives the instantaneous change in diameter of the artery and the instantaneous mean blood velocity through the sampling gate. Using these parameters and blood pressure measured with a cuff-type manometer, the computer gives WI and β. We applied this method to the carotid artery in 135 normal subjects. The mean values of W1, W2, NA, R − W1, and W1 − W2 were 8 940 ± 3 790 mmHg m/s3, 1 840 ± 880 mmHg m/s3, 27 ± 13 mmHg m/s2, 104 ± 14 ms, and 270 ± 19 ms, respectively. These values did not show a significant correlation with age. The mean value of β was 10.4 ± 4.8 and the values significantly correlated with age (men: r = 0.66, P < 0.0001; women: r = 0.81, P < 0.0001). The reproducibility was evaluated by intraobserver intrasession (IA), intraobserver intersession (IE), and interobserver intrasession variability (IO). The reproducibility of R − W1 and W1 − W2 was high: the mean coefficient of variation (mCV) of IA was less than 3%; 95% confidence limits from the mean values (CL) were less than 8% for IE and less than 4% for IO. The reproducibility of W1 and β was good: mCV for IA was less than 10%; CL for IE and IO were less than 17%. W2 and NA showed a higher variability than other indices: mCV for IA was less than 13%, and CL for IE and IO were less than 36%. However, two sessions by the same observer and two sessions by different observers were not biased. Wave intensity measurements with this system are clinically acceptable.

Left ventricular pacing minimizes diastolic ventricular interaction, allowing improved preload-dependent systolic performance

Background—Left ventricular (LV) pacing improves hemodynamics in patients with heart failure. We hypothesized that at least part of this benefit occurs by minimization of external constraint to LV filling from ventricular interaction. Methods and Results—We present median values (interquartile ranges) for 13 heart failure patients with LV pacing systems implanted for New York Heart Association class III/IV limitation. We used the conductance catheter method to measure LV pressure and volume simultaneously. External constraint was measured from the end-diastolic pressure-volume relation recorded during inferior vena caval occlusion, during LV pacing, and while pacing was suspended. External constraint to LV filling was reduced by 3.0 (4.6 to 0.6) mm Hg from 4.8 (0.6 to 7.5) mm Hg (P<0.01) in response to LV pacing; effective filling pressure (LV end-diastolic pressure minus external constraint) increased by 4.0 (2.2 to 5.8) mm Hg from 17.7 (13.3 to 22.6; P<0.01). LV end-diastolic volume increased by 10 (3 to 11) mL from 238 (169 to 295) mL (P=0.01), whereas LV end-systolic volume did not change significantly (−1 [−2 to 3] mL from 180 [124 to 236] mL, P=0.97), which resulted in an increase in stroke volume of 11 (5 to 13) mL from 49 (38 to 59) mL (P<0.01). LV stroke work increased by 720 (550 to 1180) mL · mm Hg from 3400 (2110 to 4480) mL · mm Hg (P=0.01), and maximum dP/dt increased by 120 (2 to 161) mm Hg/s from 635 (521 to 767) mm Hg/s (P=0.03). Conclusions—This study suggests a potentially important mechanism by which LV pacing may produce hemodynamic benefit. LV pacing minimizes external constraint to LV filling, resulting in an increase in effective filling pressure; the consequent increase in LV end-diastolic volume increases stroke volume via the Starling mechanism.

Left ventricular pacing improves haemodynamic variables in patients with heart failure with a normal QRS duration

Objectives: To assess whether patients with congestive heart failure (CHF) and a normal QRS duration can benefit from left ventricular (VDD-LV) pacing. Design: Cardiac resynchronisation is reserved for patients with a broad QRS duration on the premise that systolic resynchronisation is the mechanism of benefit, yet improvement from pacing correlates poorly with QRS duration. In CHF patients with a broad QRS duration, those with a high resting pulmonary capillary wedge pressure (PCWP) > 15 mm Hg benefit. In this acute haemodynamic VDD-LV pacing study, patients with CHF with a normal QRS duration were divided into two groups—patients with a resting PCWP > 15 mm Hg and patients with a resting PCWP < 15 mm Hg—to determine whether benefit is predicted by a high resting PCWP. Patients: 20 patients with CHF, New York Heart Association functional class IIb–IV, all with a normal QRS duration (⩽ 120 ms). Interventions: Temporary pacing wires were positioned to enable VDD-LV pacing and a pulmonary artery catheter was inserted for measurement of PCWP, right atrial pressure, and cardiac output. Results: In patients with a PCWP > 15 mm Hg (n  =  10), cardiac output increased from 3.9 (1.5) to 4.5 (1.65) l/min (p < 0.01), despite a fall in PCWP from 24.7 (7.1) to 21.0 (6.2) mm Hg (p < 0.001). In patients with a PCWP < 15 mm Hg there was no change in PCWP or cardiac output. Combined data showed that PCWP decreased from 17.0 (9.1) to 15.3 (7.7) mm Hg during VDD-LV pacing (p < 0.014) and cardiac output increased non-significantly from 4.7 (1.5) to 4.9 (1.5) (p  =  0.125). Conclusions: Patients with CHF with a normal QRS duration and PCWP > 15 mm Hg derive acute haemodynamic benefit from VDD-LV pacing.

Role of nitric oxide and oxidative stress in baroreceptor dysfunction in patients with chronic heart failure

Abnormalities of autonomic control of the cardiovascular system are seen in chronic heart failure (CHF) and confer a poor prognosis. Nitric oxide appears to be important in the regulation of baroreflex control in health and in disease states. The antioxidant vitamin C increases nitric oxide bioavailability in CHF. We evaluated the effects of vitamin C on baroreceptor sensitivity (BRS) by sequence analysis in 100 CHF patients and 44 control subjects. Groups of 55 CHF patients and 22 controls were randomly allocated to receive a single intravenous injection of vitamin C (2 g) or placebo. In addition, 45 CHF patients were randomly allocated to receive a 4-week course of oral vitamin C (4 g/day) or placebo. An age-related reference range for BRS was developed in 22 healthy controls matched for age and gender to the CHF group. BRS was significantly impaired in the CHF group compared with age-matched older controls and young controls (6.9 +/- 3.1, 12.5 +/- 4.9 and 21.7 +/- 9.1 mmHg/ms respectively; P < 0.001 between groups). Intravenous vitamin C acutely improved BRS in CHF patients by 24% (by 1.8 +/- 4.1 mmHg/ms; P < 0.05), but not in controls. There was no improvement in BRS in CHF patients given chronic oral vitamin C. Thus acute intravenous, but not chronic oral, vitamin C improved BRS in CHF patients. There was no effect of intravenous vitamin C in healthy subjects, suggesting that the mechanism was either by free radical scavenging or due to central effects.

Wave intensity analysis from the common carotid artery: a new noninvasive index of cerebral vasomotor tone

Cerebral vasomotor tone is difficult to assess in patients. Wave intensity analysis has been applied to resolve complex upstream and downstream events within the vascular system. We hypothesized that the backward-traveling wave measured in the common carotid artery was caused by reflection from the cerebrovascular “beach”, and that the magnitude of this reflected wave would be altered by changes in cerebral vasomotor tone. We measured common carotid arterial diameter and velocity of flow to calculate wave intensity in ten healthy male volunteers (age mean 31 ± 3 years). Applying a rebreathing technique, we were able to increase the inspired carbon dioxide concentration to a mean of 5.9% ± 1.7% and to compare baseline wave intensity readings to those recorded during hypercapnia. The magnitude of the reflected wave decreased significantly after CO2 rebreathing, from −43.0 ± 27.1 to −25.0 ± 16.9 mmHg m s−2, P = 0.02. This reduction in regative wave reflections in mid-systole during hypercapnia remained significant when it was analyzed as the reflection coefficient (the magnitude of the reflected wave normalized for the magnitude of the initiating forward wave, which fell from −2.8 ± 1.5 to −1.6 ± 1.4 ms (P = 0.01). Carotid wave reflection was significantly decreased during cerebral vasodilatation induced by increased arterial pCO2. Wave intensity may provide a simple noninvasive means of assessing changes in cerebral vasomotor tone in vivo.

Chronic oral ascorbic acid therapy worsens skeletal muscle metabolism in patients with chronic heart failure.

Chronic heart failure (CHF) is associated with abnormalities of skeletal muscle metabolism. This may be due to impaired oxygen delivery as a result of endothelial dysfunction.

Addition of candesartan to angiotensin converting enzyme inhibitor therapy in patients with chronic heart failure does not reduce levels of oxidative stress.

Angiotensin II exerts a number of harmful effects in patients with chronic heart failure (CHF) and, through an increase in oxidative stress, is thought to be critical in the development of endothelial dysfunction. Angiotensin II may be elevated in CHF despite treatment with angiotensin converting enzyme (ACE) inhibitors, producing a rationale for adjunctive angiotensin receptor blockade. We investigated whether the addition of angiotensin antagonism to ACE inhibition would reduce oxidative stress and improve endothelial function and exercise tolerance in patients with chronic heart failure.