Malcolm I. Burgess

Validation of a Generalized Transfer Function to Noninvasively Derive Central Blood Pressure During Exercise

Exercise brachial blood pressure (BP) predicts mortality, but because of wave reflection, central (ascending aortic) pressure differs from brachial pressure. Exercise central BP may be clinically important, and a noninvasive means to derive it would be useful. The purpose of this study was to test the validity of a noninvasive technique to derive exercise central BP. Ascending aortic pressure waveforms were recorded using a micromanometer-tipped 6F Millar catheter in 30 patients (56±9 years; 21 men) undergoing diagnostic coronary angiography. Simultaneous recordings of the derived central pressure waveform were acquired using servocontrolled radial tonometry at rest and during supine cycling. Pulse wave analysis of the direct and derived pressure signals was performed offline (SphygmoCor 7.01). From rest to exercise, mean arterial pressure and heart rate were increased by 20±10 mm Hg and 15±7 bpm, respectively, and central systolic BP ranged from 77 to 229 mm Hg. There was good agreement and high correlation between invasive and noninvasive techniques with a mean difference (±SD) for central systolic BP of −1.3±3.2 mm Hg at rest and −4.7±3.3 mm Hg at peak exercise (for both r=0.995; P<0.001). Conversely, systolic BP was significantly higher peripherally than centrally at rest (155±33 versus 138±32 mm Hg; mean difference, −16.3±9.4 mm Hg) and during exercise (180±34 versus 164±33 mm Hg; mean difference, −15.5±10.4 mm Hg; for both P<0.001). True myocardial afterload is not reliably estimated by peripheral systolic BP. Radial tonometry and pulse wave analysis is an accurate technique for the noninvasive determination of central BP at rest and during exercise.

Intracardiac thrombus in Behçet's disease : A systematic review

BACKGROUND Intracardiac thrombus formation is a rare but serious complication of Behçets disease. We aimed to review the clinical and pathologic correlates of cardiac thrombus formation in the context of Behçets disease. METHODS AND RESULTS A comprehensive search of the medical literature was conducted using MEDLINE including bibliographies of all selected articles. Although the disease has a unique geographic distribution, being most common in the population of the ancient Silk Route, cases complicated by intracardiac thrombus have mostly originated from the Mediterranean basin and the Middle East. Young men appear to be most at risk, with the right heart the most frequent site of involvement. The first symptoms and signs of the disease frequently precede systemic organ manifestations. In those cases in which intracardiac thrombus occurs, it is apparent in more than half of cases on first recognition of the disease. CONCLUSION A diagnosis of Behçets disease should be considered if a patient presents with a mass in the right-sided cardiac chambers, even in the absence of the characteristic clinical features of the condition. This is particularly applicable if the patient is a young man from the Mediterranean basin or the Middle East.

Automated analysis of myocardial deformation at dobutamine stress echocardiography: an angiographic validation.

OBJECTIVES We investigated the accuracy of automated analysis of myocardial deformation during dobutamine stress echocardiography (DSE). BACKGROUND The time required for segmental measurement of strain rate imaging (SRI) limits its feasibility for quantification of DSE. METHODS Myocardial deformation was assessed at DSE in 197 patients, 76 with and 61 without coronary artery disease (CAD) at angiography, and 60 at low risk of CAD. Automated deformation analysis was based on velocity gradient and segment length methods of measuring longitudinal motion within a region of interest tracked through the cardiac cycle. Results were compared with independent wall motion scoring (WMS). Patients were randomly divided; group A (n = 69) established optimal cutoffs for the parameters and group B (n = 68) tested their accuracy. RESULTS The feasibility of WMS exceeded that of both SRI methods at rest and at peak stress. In group A, the area under the receiver-operating characteristics curve of the peak systolic strain rate was 0.90 by both methods, and the optimal cutoffs for detection of CAD were -1.3 (velocity gradient) and -1.2 s(-1) (segment length). The areas under the receiver-operating characteristics curves for end-systolic strain were less (0.87) by both methods, with respective cutoffs of 9% and 8%. In group B, the velocity and segment length methods had respective sensitivities of 87% and 84% for SR, and 87% and 88% for end-systolic strain. Both significantly exceeded that of WMS in the same group (75%). CONCLUSIONS Automated analysis of myocardial deformation at DSE is feasible and accurate, and may increase the sensitivity of expert conventional reading.

Selecting patients for cardiac resynchronization therapy: the fallacy of echocardiographic dyssynchrony

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure. International guidelines unanimously endorse QRS prolongation to identify candidates for implantation, based on over 4,000 patients randomized in landmark trials. Small, observational, nonrandomized studies with surrogate end points have promoted echocardiography as a superior method of patient selection. Over 30 dyssynchrony parameters have been proposed. Most lack validation in appropriate clinical settings, including demonstration of short- and long-term reproducibility and intra- and interobserver variability. Prospective multicenter trials have proved informative in unexpected ways. In core laboratories, parameters exhibit striking variability, poor reproducibility, and limited predictive power. We are concerned that many centers today are using these techniques to select patients for CRT. Publication density and bias have misinformed clinical decision making. Echocardiographic parameters have no place in denying potentially life-saving treatment or in exposing patients to unnecessary risks and draining health care resources. Such measures should not stray beyond the research environment unless validated in randomized trials with robust clinical end points. The electrocardiogram remains a simple, inexpensive, and reproducible tool that identifies patients likely to benefit from CRT. Patient selection must use the parameter prospectively validated in landmark clinical trials: the QRS duration.

Measurement of left ventricular dyssynchrony in patients with ischaemic cardiomyopathy: a comparison of real-time three-dimensional and tissue Doppler echocardiography

Background: Real-time three-dimensional echocardiography (RT3DE) is an alternative modality to tissue Doppler imaging (TDI) for assessment of intraventricular dyssynchrony but its role is yet to be defined. Objectives: To (1) compare RT3DE and TDI for assessment of intraventricular dyssynchrony; (2) determine whether the two techniques agreed regarding the magnitude of dyssynchrony and identification of the site of maximal mechanical delay; and (3) investigate the reason for disagreement. Patients: 100 patients with ischaemic cardiomyopathy. Setting: Tertiary referral cardiac unit. Main outcome measures: Dispersion in time interval from QRS onset to peak sustained systolic tissue velocity by TDI (SD-TTV) and to minimal systolic volume by RT3DE (SD-T3D) between 12 ventricular segments. Results: RT3DE image quality was adequate for measurement of SD-T3D in 77 (77%) patients. In the whole population, SD-TTV was 40 (20) ms and SD-T3D was 8.3% (3.4%). RT3DE identified a smaller proportion of patients as having significant dyssynchrony than TDI (49 (64%) patients vs 32 (42%) patients; p<0.01). The correlation between SD-TTV and SD-T3D was poor (r = 0.11, p = NS). There was concordance between TDI and RT3DE in identifying the site of maximal mechanical delay in 12 (16%) patients. Validating the two techniques with anatomical M-mode (AMM) as a parameter of radial timing revealed better agreement with RT3DE than with TDI (χ2 = 11.8, p = 0.001). Conclusion: In patients with ischaemic cardiomyopathy, TDI and RT3DE show poor agreement for evaluating the magnitude of intraventricular dyssynchrony and the site of maximal mechanical delay. This may partly relate to their respective assessment of longitudinal versus radial timing.

Relationship between myocardial perfusion and dysfunction in diabetic cardiomyopathy: a study of quantitative contrast echocardiography and strain rate imaging

Objective: To use quantitative myocardial contrast echocardiography (MCE) and strain rate imaging (SRI) to assess the role of microvascular disease in subclinical diabetic cardiomyopathy. Methods: Stress MCE and SRI were performed in 48 patients (22 with type II diabetes mellitus (DM) and 26 controls), all with normal left ventricular systolic function and no obstructive coronary disease by quantitative coronary angiography. Real-time MCE was acquired in three apical views at rest and after combined dipyridamole–exercise stress. Myocardial blood flow (MBF) was quantified in the 10 mid- and apical cardiac segments at rest and after stress. Resting peak systolic strain rate (SR) and peak systolic strain (ε) were calculated in the same 10 myocardial segments. Results: The DM and control groups were matched for age, sex and other risk factors, including hypertension. The DM group had higher body mass index and left ventricular mass index. Quantitative SRI analysis was possible in all patients and quantitative MCE in 46 (96%). The mean ε, SR and MBF reserve were all significantly lower in the DM group than in controls, with diabetes the only independent predictor of each parameter. No correlation was seen between MBF and SR (r  =  −0.01, p  =  0.54) or between MBF and ε (r  =  −0.20, p  =  0.20). Conclusions: Quantitative MCE shows that patients with diabetes but no evidence of obstructive coronary artery disease have impaired MBF reserve, but abnormal transmural flow and subclinical longitudinal myocardial dysfunction are not related.

Clinical significance of Tricuspid valve dysfunction after orthotopic Heart transplantation

OBJECTIVES Tricuspid regurgitation (TR) is common after heart transplantation (OHT), but its clinical relevance is undetermined. This study documents the clinical progress of patients with TR after OHT in relation to the severity of TR. METHODS We studied 238 transplant recipients who had survived for at least 12 months after OHT. Tricuspid regurgitation was graded clinically and by assessing regurgitant jet area. Recipients were divided into those with no TR Group 1 (n = 64), those with sub-clinical TR (TR absent clinically and regurgitant jet area <25%, Group 2 (n = 89), and those with clinical TR (with clinical TR or regurgitant jet area > or =25%, Group 3 (n = 85). RESULTS We found no significant difference among the groups in terms of age, or pre-operative events. At 12 months after OHT, mean right atrial and pulmonary artery pressures were higher in Group 3 than in Group 1 or Group 2 (p = 0.005 and 0.03, respectively). Right ventricular end-diastolic and end-systolic volumes were smaller for recipients in Groups 1 and 2 compared with those in Group 3 (p = 0.01 and 0.02). The annual development of renal impairment was 0.019 (95% confidence interval [CI], 0.014-0.029), 0.026 (95% CI, 0.022-0.62), and 0.613 (95% CI, 0.346-0.756) in Groups 1, 2, and 3, respectively (p = 0.02). At the most recent follow-up, mean New York Heart Association class for Group 1 was 1.4, for Group 2 was 1.7, and for Group 3 was 2.7 (p = 0.04). CONCLUSIONS The integrity of the tricuspid valve has a significant impact on long-term clinical progress of OHT recipients. Recipients with significant TR are more symptomatic and have poorer right-sided heart function compared with those with mild or no TR.

Cardiac transplantation for cardiomyopathy and ischemic heart disease: differences in outcome up to 10 years

BACKGROUND Ischemic heart disease (IHD) and cardiomyopathy (CM) are the most common indications for heart transplantation. The aim of this study was to investigate the difference in clinical outcome between these two groups. METHODS At our institution between 1987 and 1998 transplantation was performed in 133 patients with IHD and 87 with CM. Follow-up was complete for all patients (mean 87 months). RESULTS Mean age at time of surgery was 51 +/- 5 years for IHD versus 39 +/- 9 years for CM recipients (p = 0.02). There was no difference in donor age, donor gender, or pre-operative hemodynamics between the two groups. The operative mortality was 11.2% in IHD recipients and 10.6% in CM recipients (p = 0.9). No differences were observed in intra-cardiac pressures or incidence of renal dysfunction, infection, or malignancy between the two groups. The incidence of peripheral vascular incidents was significantly higher for IHD recipients (13% vs 3%, p = 0.02). At 10 years, the incidence of coronary artery disease was 35% and 9%, respectively (p = 0.02). Mean NYHA status was 2.0 +/- 0.3 and 1.1 +/- 0.2 for IHD and CM recipients, respectively (p = 0.013). The actuarial survival at 1, 5, and 10 years was 77%, 62%, and 39% for IHD recipients compared with 85%, 82%, and 80% for CM recipients (p = 0.7, p < 0.0001 and p < 0.0001, respectively). CONCLUSION After heart transplantation, medium- and long-term outcome is significantly better for CM than IHD recipients. In view of limited donor availability, it is appropriate to explore more vigorously alternative treatments for patients with severe ischemic left ventricular dysfunction.

Heart transplantation for peripartum cardiomyopathy: a report of three cases and a literature review.

Peripartum cardiomyopathy is a devastating medical condition and carries a mortality of up to 60% with medical treatment. The authors describe their experience of successful outcome of three cases with heart transplantation and review the literature. The importance of performance of endomyocardial biopsy for all peripartum cardiomyopathy patients is emphasized. It is recommended that heart transplantation should only be offered to myocarditis negative patients.

Transforming growth factor β and diastolic left ventricular dysfunction after heart transplantation: Echocardiographic and histologic evidence

BACKGROUND The mechanism for chronic left ventricular diastolic dysfunction in the non-rejecting cardiac allograft has not been fully studied. OBJECTIVES The purposes of this study were to analyze the significance and frequency of left ventricular diastolic dysfunction after heart transplantation and to examine the involvement of fibrotic cytokines (transforming growth factor beta [TGF-beta]) in development of clinical and echocardiographic changes in cardiac allograft recipients. METHODS We studied 152 heart transplant recipients who had survived for at least 24 months. We compared histopathologic findings (staining of endomyocardial biopsy specimens using hematoxylin and eosin, and polyclonal antibodies expressed as TGF-beta score), left ventricular function (Doppler echocardiography), and clinical course (New York Heart Association [NYHA] status). We classified patients into Group 1 (n = 41 recipients) with a restrictive filling pattern, mitral deceleration time (MDT) <140 milliseconds, and Group 2 (n = 111 recipients), MDT >or=140 milliseconds. RESULTS The MDT was 122 +/- 7 milliseconds in Group 1 compared with an MDT of 177 +/- 17 milliseconds in Group 2 (p = 0.0003). Group 1 showed significant immunohistochemical staining in endomyocardial biopsy specimens (a mean TGF-beta score of 9.1 +/- 1.2 for Group 1 compared with a mean TGF-beta score of 3.6 +/- 0.8 for Group 2 p = 0.001). The TGF-beta expression correlated inversely with both MDT and isovolumic relaxation time (r = -0.77, p = 0.0004, and r = -0.69, p = 0.004, respectively). Mean NYHA status in Group 1 recipients was 2.2 +/- 1.1 compared with 1.37 +/- 0.6 for Group 2 (p = 0.006). CONCLUSIONS Transforming growth factor beta expression in cardiac allografts is associated with impaired left ventricular diastolic function. The pathogenesis of diastolic dysfunction may be an aberrant repair process after rejection-caused TGF-beta expression in the allograft.