Determination of the optimal echocardiographic scoring system to quantify carcinoid heart disease.

BACKGROUND: Carcinoid heart disease (CHD) is an important complication of metastatic neuroendocrine disease, requiring regular monitoring to enable intervention prior to right heart failure. We aimed to identify the most appropriate echocardiographic scoring systems for the quantitative assessment of CHD. METHODS: In this prospective study conducted between April and October 2012 in two European Neuroendocrine Tumor Society (ENETS) Centres of Excellence, patients with neuroendocrine tumours with liver metastases and/or carcinoid syndrome underwent transthoracic echocardiography and blood sampling for serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and plasma 5-hydroxyindoleacetic acid (5-HIAA). Each patient was assessed according to six echocardiographic scoring systems. The individual scoring systems' feasibility, observer variability, sensitivity, specificity and correlation with the concentration biomarkers were determined. RESULTS: 100 patients were included; 21% had echocardiographic evidence of CHD. All scores discriminated highly between those with/without CHD, with no single score performing significantly better than another. The severity, determined using all of the scoring systems, correlated with the concentration of both biomarkers, but the strongest correlations were seen between the Bhattacharyya score and serum NT-proBNP. CONCLUSION: All scoring systems are comparable in terms of sensitivity and specificity for the detection of CHD. There is a variation in the feasibility of the scoring systems due to varying complexity of the score components. All scores correlate with NT-proBNP and plasma 5-HIAA. The Westberg score appears to be the most optimal scoring system for use in screening of CHD whereas the more complex scoring systems are more suited to the patient with established disease who may require surgical intervention.

The association of a panel of biomarkers with the presence and severity of carcinoid heart disease: a cross-sectional study.

PURPOSE: Metastatic neuroendocrine tumors secrete serotonin and other vasoactive substances that are responsible for carcinoid syndrome and carcinoid heart disease. We sought to evaluate the discriminatory utility of diagnostic biomarkers in determining the presence and severity of carcinoid heart disease in patients with metastatic neuroendocrine tumors. PATIENTS AND METHODS: A cross-sectional study of patients with neuroendocrine tumors with documented liver metastases and/or carcinoid syndrome between April 2009-October 2012 in 5 tertiary referral centers. Serum was analyzed for Chromogranin A, Chromogranin B and N-terminal pro Brain Natriuretic Peptide (NT-proBNP). Plasma was analyzed for Neurokinin A and 5-Hydroxyindoleacetic acid (5HIAA). Echocardiography was used to determine the presence and severity of carcinoid heart disease. Non-parametric receiver operating characteristic curves were constructed for biomarkers, and the area under the curve determined. The severity of cardiac involvement was correlated with the concentration of each biomarker. RESULTS: A total of 187 patients were identified of whom 37 (20%) had carcinoid heart disease. Significantly higher median values of all biomarkers were found in the patients with cardiac involvement. NT-proBNP and plasma 5HIAA had the highest areas under the curve for the prediction of carcinoid heart disease [NT-proBNP 0.82 (95% confidence interval 0.74-0.90, p<0.0001) and 5HIAA 0.85 (95% confidence interval 0.78-0.92, p<0.0001]. NT-proBNP was moderately correlated (r = 0.48, p<0.001) whereas plasma 5HIAA was only weakly correlated (r = 0.34, p<0.001) with the echocardiographic severity score. CONCLUSION: NT-proBNP and plasma 5HIAA are both sensitive and specific biomarkers for the presence of carcinoid heart disease whereas only NT-proBNP is moderately correlated with disease severity.

The optimal use of cardiac imaging in the quantification of carcinoid heart disease.

Carcinoid heart disease is a rare cause of right-sided valvular dysfunction, primarily mediated by serotonin. It is an important complication in patients with carcinoid syndrome and occurs in 20-50% of such patients. Echocardiography is the main technique used for the assessment of carcinoid heart disease, but other imaging modalities are also important, particularly in the quantification of the severity of the disease. We sought to review the role of cardiac imaging in the assessment of carcinoid heart disease.

Endocarditis in a large district general hospital: A study of the microbiological spectrum between 2000 and 2011.

Infective endocarditis is one of three common cardiac infections in the United Kingdom, in addition to myocarditis and pericarditis, with a reported incidence of 1.7 to 6.2 cases per 100,000 patient years. Infective endocarditis can often have serious consequences and a wide variety of organisms may be the causative pathogen. There are little published data regarding the exact spectrum of organisms that cause endocarditis in the United Kingdom and whether organisms such as streptococci still dominate. In the present study, all cases of endocarditis at the authors' institution, representing a typical nontertiary centre, were retrospectively examined and audited to provide a snapshot of the organism spectrum in these patients. The cases of more than 120 patients who were coded as having endocarditis by the institution's clinical coding department during the period between December 2000 and January 2011 were examined. Microbiological tests and clinical case notes of all patients were reviewed. Of the 101 patients diagnosed with and treated for endocarditis, 64 were male, with a mean age of 60.57 years. The most common organisms identified were Streptococcus species (31%), Staphylococcus aureus (27%) and Enterococcus faecalis (21%). The organisms with the highest associated mortality rate were S aureus and the 'other organism' group, which included non-HACEK group (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella species) pathogens such as Candida albicans. Streptococcus species and S aureus remain the main cause of endocarditis in a typical hospital setting in the United Kingdom, although in a smaller proportion of cases than historical data suggests. Overall, mortality remains high, and the clinician should remain vigilant to endocarditis in any patient with a positive blood culture because the number of cases of endocarditis caused by less typical organisms are increasing.

Functional significance of the conus artery as a collateral to an occluded left anterior descending artery demonstrated by stress echocardiography.

Dobutamine stress echocardiography is a sensitive tool used for the detection of ischaemia. However, on occasion, there is a discrepancy between angiographic lesion severity and what would be expected from the abnormalities seen at stress echo. When stress echo underestimates severity it may be the case that collateral vessels play a significant role in preserving myocardial function. We present a case study where collateral flow in an occluded left anterior descending artery (LAD) is demonstrated as coming from the conus branch; and where stress echocardiography shows the relative preservation of function in the affected segments. Although rarely observed in clinical practice, the conus artery has occasionally been noted as a source of collateral blood flow. For the first time in the literature, this case demonstrates that the conus can provide functionally significant collateral blood supply to an occluded LAD.

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-T(TV)) and to minimal systolic volume by RT3DE (SD-T(3D)) between 12 ventricular segments. RESULTS: RT3DE image quality was adequate for measurement of SD-T3D in 77 (77%) patients. In the whole population, SD-T(TV) 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-T(TV) 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 (chi2 = 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.

Role of diastolic dyssynchrony in the delayed relaxation pattern of left ventricular filling.

We investigated the extent to which diastolic dyssynchrony contributes to the delayed relaxation pattern of left ventricular filling and limitation in exercise capacity. In 100 patients with diabetes, preserved left ventricular systolic function, normal filling pressure, and no coronary disease, we measured magnitude of early diastolic tissue lengthening (tissue velocity and strain rate) and diastolic dyssynchrony (SD in QRS to peak early diastolic tissue velocity interval across 4 basal myocardial segments). From transmitral flow patients were divided into those with normal filling (50 patients) and delayed relaxation (50 patients). Myocardial lengthening was reduced and SD in interval from QRS onset to peak early diastolic tissue velocity across all segments was higher in patients with delayed relaxation compared with control patients. Myocardial lengthening was the only predictor of delayed relaxation and correlation with exercise capacity was better for lengthening indices than SD in interval from QRS onset to peak early diastolic tissue velocity across all segments. Therefore, in this group a reduced rate of myocardial lengthening plays a more important role in delayed relaxation than diastolic dyssynchrony.

Prognostic value of intraventricular dyssynchrony according to clinical stage of left ventricular impairment.

Intraventricular dyssynchrony has prognostic implications in patients who have severe functional limitation and decreased ejection fraction. Patients with less advanced cardiac disease often exhibit intraventricular dyssynchrony, but there is little available information about its prognostic relevance in such patients. We investigated the prognostic effect of intraventricular dyssynchrony on outcome in 318 patients with known or suspected coronary artery disease who were classified according to the presence or absence of left ventricular dysfunction and heart failure symptoms. Mortality was considered the primary end point over a median follow-up of 56 months, and a Cox proportional hazards model was used for survival analysis. Despite a low prevalence (8%) of left bundle branch block, there was a high prevalence of intraventricular dyssynchrony even in patients without symptomatic heart failure. The magnitude of intraventricular dyssynchrony correlated poorly with QRS duration (r = 0.25), end-systolic volume index (r = 0.27), and number of scar segments (r = 0.25). There were 58 deaths during follow-up. Ventricular volume, ischemic burden, and magnitude of intraventricular dyssynchrony predicted outcome, but magnitude of intraventricular dyssynchrony was an independent predictor of survival only in patients with asymptomatic left ventricular dysfunction. In conclusion, patients with known or suspected coronary artery disease have a high prevalence of intraventricular dyssynchrony. Although ventricular volume, ischemic burden, and intraventricular dyssynchrony are potentially important prognostic markers, the relative importance of intraventricular dyssynchrony changes with the clinical setting and may be greatest in patients with preclinical disease.

Diastolic stress echocardiography: hemodynamic validation and clinical significance of estimation of ventricular filling pressure with exercise.

OBJECTIVES: Our study attempted to validate a Doppler index of diastolic filling (E/E') during exercise with simultaneously measured left ventricular diastolic pressure (LVDP), investigate its association with exercise capacity, and understand which patients to select for testing. BACKGROUND: The ratio of early diastolic transmitral velocity to early diastolic tissue velocity approximates LVDP at rest, but there is limited validation of exercise E/E' with invasive hemodynamic measurement, and its clinical implications are unclear. METHODS: The ratio of early diastolic transmitral velocity to early diastolic tissue velocity was measured at rest and during supine cycle ergometry in 37 patients undergoing left heart catheterization. In addition to correlation between invasive and estimated LVDP, the accuracy of different cutoffs for identification of elevated LVDP (>15 mm Hg) was determined at both rest and exercise. Doppler index of diastolic filling was also measured at rest and immediately after maximal treadmill exercise in 166 patients to investigate the association between exercise E/E' and exercise capacity (<8 metabolic equivalents [METs]). RESULTS: In patients undergoing invasive measurement, nine (24%) had elevation of LVDP only during exercise. There was a good correlation between E/E' and LVDP at rest (r = 0.67) and during exercise (r = 0.59), and the regressions at rest and exercise corresponded closely. Receiver-operator curve analysis indicated that a cutoff value of 13 for exercise E/E' identified patients with an elevated LVDP during exercise. A post-exercise E/E' >13 was highly specific (90%) for reduced exercise capacity, and even after classification of resting E/E', exercise E/E' permitted classification of patients with exercise capacity <8 METs or > or =8 METs. CONCLUSIONS: The ratio of early diastolic transmitral velocity to early diastolic tissue velocity correlates with invasively measured LVDP during exercise. It can be used to reliably identify patients with elevated LVDP during exercise and reduced exercise capacity.

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.

Can the index of myocardial performance be used to detect acute cellular rejection after heart transplantation?

The index of myocardial performance (IMP), combining systolic and diastolic function, was measured in 50 orthotopic heart transplant recipients to determine if it could be used to detect acute rejection. It was calculated as the sum of the isovolumic contraction time (IVCT) and isovolumic relaxation time (IVRT) divided by the ejection time. Comparison of intrarecipient changes in Doppler intervals between rejection and nonrejection states demonstrated an increase in IVCT and decrease in IVRT during rejection with no significant change in the IMP. Rejection is likely to be best detected by assessing these parameters independently rather than by measuring the IMP.

Transforming growth factor beta 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.

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.

Comparison of echocardiographic markers of right ventricular function in determining prognosis in chronic pulmonary disease.

Right ventricular (RV) dysfunction determines prognosis in patients with chronic pulmonary disease. We examined the relative prognostic potential of measures of systolic, diastolic, and global RV function in 87 patients with chronic pulmonary disease. Systolic function was evaluated by measuring RV dimensions, diastolic function by pulsed wave Doppler of the tricuspid flow profile, and global function by the Tei index. After 15.5 months follow-up, 47 patients had died. Univariate analysis demonstrated that both clinical and echocardiographic variables predicted survival. In the multivariate model both RV end-diastolic diameter index and velocity of late diastolic filling were independent predictors of survival. Receiver operator characteristic analysis demonstrated that a composite model combining these 2 measures provided the most powerful prognostic information. Echocardiographic indices of RV function identify patients with pulmonary disease at high risk and provide incremental prognostic information over and above that supplied by clinical data.