Feasibility and reproducibility of off-line tissue Doppler measurement of regional myocardial function during dobutamine stress echocardiography.

AIMS: Off-line post-processing of colour tissue Doppler from digital loops may allow objective quantification of dobutamine stress echocardiography. We assessed the reproducibility of off-line measurements of regional myocardial velocities. METHODS AND RESULTS: Nine observers analysed 10 studies, each making 2400 observations. Coefficients of variation in basal segments from apical windows, at rest and maximal stress, were 9-14% and 11-18% for peak systolic velocity, 16-18% and 17-19% for time-to-peak systolic velocity, 9-17% and 18-24% for systolic velocity time integral, and 18-23% and 21-27% for systolic acceleration. Coefficients of variation for diastolic velocities in basal segments at rest were 11-40%. Coefficients of variation for peak systolic velocity were 10-24% at rest and 14-28% at peak in mid segments, and 19-53% and 29-69% in apical segments. From parasternal windows coefficients of variation for peak systolic velocity were 14-16% in basal posterior, and 19-29% in mid-anterior segments. High variability makes measurement unreliable in apical and basal anterior septal segments. The feasibility of obtaining traces was tested in 92 subjects, and >90% in all basal and mid segments apart from the anterior septum. CONCLUSION: Quantification of myocardial functional reserve by off-line analysis of colour tissue Doppler acquired during dobutamine stress is feasible and reproducible in 11 segments of the left ventricle. The most reliable measurements are systolic velocities of longitudinal motion in basal segments.

Effects of nitric oxide synthase inhibition on Basal function and the force-frequency relationship in the normal and failing human heart in vivo.

BACKGROUND: Nitric oxide (NO) exerts autocrine/paracrine effects on cardiac function, including alterations of the inotropic state. In vitro studies suggest that NO modulates the myocardial force-frequency relationship. Basal left ventricular (LV) contractility is depressed and the force-frequency relationship is blunted in human heart failure, and it is speculated that an increase in NO production is involved. METHODS AND RESULTS: We compared the effects of intracoronary NO synthase inhibition with N(G)-monomethyl-L-arginine (L-NMMA; 25 micromol/min) on basal LV function and the response to incremental atrial pacing in patients with dilated cardiomyopathy (n=11; mean age, 51 years) and in control subjects with atypical chest pain and normal cardiac function (n=7; mean age, 54 years). In controls, L-NMMA significantly reduced basal LV dP/dt(max) (from 1826 to 1578 mm Hg/s; P<0.002), but had no effect on heart rate, mean aortic pressure, or right atrial pressure. Pacing-induced increases in LV dP/dt(max) were unaltered by L-NMMA. In patients with dilated cardiomyopathy, L-NMMA had no effect on baseline LV dP/dt(max) (from 1313 to 1337 mm Hg/s; P=NS). The blunted pacing-induced rise in LV dP/dt(max) in these patients was unaltered by L-NMMA. CONCLUSION: Endogenous NO has a small baseline positive inotropic effect in the normal human heart, which is lost in heart failure patients. NO does not significantly influence the force-frequency relationship in either the normal or failing human heart in vivo. Because this study was performed in patients with moderate heart failure, whether the findings apply to subjects with more severe heart failure requires further investigation.

Long-term results after aortic valve replacement in patients with congestive heart failure. Homografts vs prosthetic valves.

OBJECTIVES: The aim of this study was to assess the influence of valve substitute (homograft vs prosthetic valve) on the long-term survival and late valve-related complication rates following aortic valve replacement in patients with aortic valve disease and congestive heart failure. BACKGROUND: The effect of choice of valve substitute on outcome after aortic valve replacement in patients with pre-operative heart failure is unknown. The superior haemodynamic profile of homografts may be of particular benefit. METHODS: We retrospectively analysed pre-operative, operative and follow-up data on 518 adults in functional classes III and IV, who, over the 25 years 1969-1993, had their initial aortic valve replacement at Harefield hospital. Follow-up conducted during 1996 to April 1997 and totalling 4439 patient-years was 96.1% complete. Using multivariate analysis, independent risk factors for different complications and mortality were defined. RESULTS: Overall 5-, 10- and 20-year survival was 80+/-2%, 62+/-2% and 30+/-3%, respectively, with no significant difference between valve types. However, homografts (n=381) independently reduced the rate of serious complications and cardiac death, whereas mechanical valves were an independent adverse risk factor for late mortality. The rates of anticoagulant-related bleeding and thromboembolism were increased by mechanical valves, whereas primary tissue failure was the main complication of homografts. CONCLUSIONS: Long-term outcome of homograft aortic valve replacement in patients with congestive heart failure is acceptable, with a reduced rate of serious complications and cardiac death. Further improvements would be expected if the rate of primary tissue failure could be reduced.

Effects of sulphydryl- and non-sulphydryl-containing ACE inhibitors on left ventricular relaxation in the isolated guinea pig heart.

ACE inhibitors exert both acute and chronic beneficial effects on cardiac function (e.g remodelling, diastolic dysfunction). We have previously reported that the ACE inhibitor captopril induces selective left ventricular (LV) relaxant effects in the isolated ejecting guinea pig heart. The aim of the present study was to further investigate the mechanism of the captopril-induced changes in early LV relaxation by comparing the effects of two sulphydryl and two non-sulphydryl containing ACE inhibitors in the same experimental preparation. Isolated ejecting guinea pig hearts were studied under conditions of constant loading and heart rate. LV pressure was monitored by a 2F micromanometer-tipped catheter transducer inserted in the LV cavity. The sulphydryl-containing ACE inhibitors captopril and zofenaprilat enhanced early LV relaxation, whereas the non-sulphydryl-containing ACE inhibitors lisinopril and quinaprilat did not. The effects of captopril and zofenaprilat were attenuated both by the nitric oxide-scavenger haemoglobin and the bradykinin B2-kinin receptor antagonist HOE 140. Neither the oxygen free-radical scavenger superoxide dismutase nor the sulphydryl-containing compound N-acetyl cysteine administered together with lisinopril had any effect on LV relaxation. These data demonstrate that inhibition of intra-cardiac ACE activity may acutely modulate LV relaxation through increased activity of the bradykinin-nitric oxide pathway. The presence of a sulphydryl group on the relevant ACE inhibitor appears to be essential for this LV relaxant effect.

The cardiac endothelium: cardioactive mediators.

Endothelial cells within the heart release a number of substances that modulate myocardial contractile function. These agents include nitric oxide, endothelin, prostanoids, adenylpurines, and other substances that have so far been characterized only in bioassay studies. A notable feature of many of these agents is that they influence contractile behavior predominantly by modifying cardiac myofilament properties rather than altering cytosolic Ca2+ transients. A consequence of this subcellular action is often a disproportionate effect on myocardial relaxation and diastolic tone. The paracrine modulation of cardiac myocyte function by endothelial cell factors is likely to be an important mechanism contributing to the overall regulation of cardiac contractile function, both physiologically and in pathological states.

Enhancement of left ventricular relaxation in the isolated heart by an angiotensin-converting enzyme inhibitor.

BACKGROUND: ACE inhibitors exert both acute and chronic beneficial effects on cardiac function (eg, remodeling, diastolic dysfunction) in experimental studies and in patients. They inhibit the formation of angiotensin II as well as the degradation of endogenous bradykinin. We recently reported that bradykinin induces selective left ventricular (LV) relaxant effects in isolated hearts via the release of nitric oxide. The present study examined the direct effects of interaction between the ACE inhibitor captopril and endogenous bradykinin on cardiac contractile function. METHODS AND RESULTS: Isolated ejecting guinea pig hearts were studied under conditions of constant loading and heart rate. LV pressure was monitored by a 2F micromanometer-tipped catheter. Captopril (1 mumol/L, n = 9) caused a progressive acceleration of LV relaxation without significantly affecting early systolic parameters (eg, LV dP/dtmax) or coronary flow. These effects were inhibited by the nitric oxide scavenger hemoglobin (1 mumol/L, n = 5) or by the B2-kinin receptor antagonist HOE140 (10 nmol/L, n = 5). In the presence of captopril, bradykinin (0.1 nmol/L, n = 6) markedly accelerated LV relaxation (significantly more than captopril alone), whereas bradykinin alone (0.1 nmol/L, n = 6) had no effect. CONCLUSIONS: These data indicate that the ACE inhibitor captopril causes an acute and selective enhancement of LV relaxation independent of changes in coronary flow, probably via an endogenous bradykinin/nitric oxide pathway.

The successful surgical repair of a ruptured interventricular septum following a myocardial infarct in an 89 year old man.

This case report describes the successful repair of an acquired ventricular septal defect following an anterior full thickness myocardial infarct in an 89 year old man. Four months after the infarct the patient was in severe congestive cardiac failure (NYHA Class IV), despite medical treatment, with signs of a ventricular septal defect. This was confirmed by echodoppler and cardiac catheterization. Surgical repair of the ventricular septal defect was performed. He made an uncomplicated recovery and two and a half years later is well and active. We believe he is the oldest patient who has had this operation successfully.