Irene Zeng

Assessments of Right Ventricular Volume and Function Using Three-Dimensional Echocardiography in Older Children and Adults With Congenital Heart Disease: Comparison With Cardiac Magnetic Resonance Imaging

BACKGROUND The utility of three-dimensional echocardiography (3DE) for right ventricular (RV) assessment is uncertain in older children and adults with congenital heart disease (CHD), in whom the right ventricle is often dilated and dysfunction is common. METHODS RV assessments using 3DE were compared with manual tracing and automated border detection (ABD) with magnetic resonance imaging (MRI) as the reference method. Twenty-eight of 54 consecutive patients (52%; median age, 17 years) with CHD had adequate three-dimensional echocardiographic data sets for analysis. RESULTS There were wide ranges of RV size (mean RV end-diastolic volume index, 143 +/- 43 mL/m(2)) and function (mean RV ejection fraction [EF], 48 +/- 10%) on MRI. End-diastolic volume was underestimated on 3DE by 20% (P < .001) and to a greater degree in larger ventricles (P < .001). There was no significant difference in EF measurements between 3DE methods and MRI except for ABD (-2.6 +/- 6, P = .03). The mean analysis time for ABD was 5 minutes, compared with 19 minutes for manual tracing (P < .0001). CONCLUSION Approximately half the patients with CHD had adequate three-dimensional echocardiographic images. Three-dimensional echocardiography accurately estimated EF but underestimated volume, particularly when the right ventricle was dilated. ABD minimally underestimated EF but offered a significant reduction in analysis time.

Longitudinal left ventricular contractile dysfunction after exercise in aortic stenosis

Objective: To determine whether longitudinal left ventricular systolic function measured by Doppler tissue imaging (DTI) after exercise can identify early left ventricular dysfunction in asymptomatic patients with moderate–severe aortic stenosis. Design: Case–control study. Setting: Outpatient cardiology departments. Patients: 20 patients with aortic stenosis, with or without equivocal symptoms, a peak aortic valve velocity ⩾3 m/s, and left ventricular ejection fraction >50% and 15 aged-matched normal controls. Interventions: Echocardiogram performed at rest and immediately after treadmill exercise. Main outcome measures: The peak systolic velocity of the lateral mitral annulus (S’) by DTI at rest and immediately after exercise, exercise capacity, exercise systolic blood pressure and the plasma level of B-type natriuretic peptide (BNP). Results: For patients with aortic stenosis, mean (SD) aortic valve area was 0.95 (0.3) cm2. At rest, S’ was similar for patients with aortic stenosis and controls, respectively (8.5 (1.5) vs 9.1 (1.8) cm/s, p = 0.15). However, after exercise, S’ (12.2 (3.2) vs 17 (2.8) cm/s, p<0.001) and the increase in S’ between rest and exercise (4 (3) vs 7.9 (1.5) cm/s, p<0.001) were lower in patients with aortic stenosis. In patients with aortic stenosis, a smaller increase in S’ after exercise was associated with lower exercise capacity (r = 0.5, p = 0.02), a smaller increase in exercise systolic blood pressure (r = 0.6, p = 0.005) and higher plasma level of BNP (r = 0.66, p = 0.002). Conclusion: In asymptomatic patients with moderate–severe aortic stenosis a lower than normal increase in peak systolic mitral annular velocity after treadmill exercise is a marker of early left ventricular systolic dysfunction.

Optimising echocardiographic screening for rheumatic heart disease in New Zealand: not all valve disease is rheumatic.

AIMS Echocardiography detects a greater prevalence of rheumatic heart disease than heart auscultation. Echocardiographic screening for rheumatic heart disease combined with secondary prophylaxis may potentially prevent severe rheumatic heart disease in high-risk populations. We aimed to determine the prevalence of rheumatic heart disease in children from an urban New Zealand population at high risk for acute rheumatic fever. METHODS AND RESULTS To optimise accurate diagnosis of rheumatic heart disease, we utilised a two-step model. Portable echocardiography was conducted on 1142 predominantly Māori and Pacific children aged 10-13 years. Children with an abnormal screening echocardiogram underwent clinical assessment by a paediatric cardiologist together with hospital-based echocardiography. Rheumatic heart disease was then classified as definite, probable, or possible. Portable echocardiography identified changes suggestive of rheumatic heart disease in 95 (8.3%) of 1142 children, which reduced to 59 (5.2%) after cardiology assessment. The prevalence of definite and probable rheumatic heart disease was 26.0 of 1000, with 95% confidence intervals ranging from 12.6 to 39.4. Portable echocardiography overdiagnosed rheumatic heart disease with physiological valve regurgitation diagnosed in 28 children. A total of 30 children (2.6%) had non-rheumatic cardiac abnormalities, 11 of whom had minor congenital mitral valve anomalies. CONCLUSIONS We found high rates of undetected rheumatic heart disease in this high-risk population. Rheumatic heart disease screening has resource implications with cardiology evaluation required for accurate diagnosis. Echocardiographic screening for rheumatic heart disease may overdiagnose rheumatic heart disease unless congenital mitral valve anomalies and physiological regurgitation are excluded.

The Antiplatelet Effect of Higher Loading and Maintenance Dose Regimens of Clopidogrel: The PRINC (Plavix Response in Coronary Intervention) Trial

OBJECTIVES This study evaluated the antiplatelet effect of a higher loading and maintenance dose regimen of clopidogrel and a possible drug interaction with verapamil. BACKGROUND Clopidogrel loading doses above 600 mg have not resulted in more rapid or complete platelet inhibition. Higher maintenance dosages may be more effective than 75 mg/day. METHODS A double-blind, randomized, placebo-controlled trial was undertaken in 60 patients undergoing percutaneous coronary intervention. All patients received clopidogrel 600 mg at the start of the procedure. Using a 2 x 2 design, patients were allocated to clopidogrel 600 mg given 2 h later or matching placebo, and to verapamil 5 mg intra-arterial or placebo. Platelet function was measured using the VerifyNow P2Y12 analyzer (Accumetrics Ltd., San Diego, California) at 2, 4, and 7 h. Patients were further randomized to receive a clopidogrel 75 or 150 mg once daily, with platelet function assessed after 1 week. RESULTS Two hours after the second dose of clopidogrel or placebo, platelet inhibition was 42 +/- 27% with clopidogrel, compared with 24 +/- 22% with placebo (p = 0.0006). By 5 h after the second dose, platelet inhibition was 49 +/- 30% with clopidogrel, compared with 29 +/- 22% with placebo (p = 0.01). No drug interaction was seen with verapamil. A clopidogrel maintenance dosage of 150 mg daily for 1 week resulted in greater platelet inhibition than 75 mg daily (50 +/- 28% vs. 29 +/- 19%, p = 0.01). CONCLUSIONS In an unselected population undergoing percutaneous coronary intervention a clopidogrel 1,200-mg loading dose, given as two 600-mg doses 2 h apart, results in more rapid and complete platelet inhibition than a single 600-mg dose. A maintenance dosage of 150 mg daily produces greater platelet inhibition than 75 mg daily. (The PRINC trial; ACTRN12606000129583).

Noncardiac Surgery and Bleeding After Percutaneous Coronary Intervention

Background—The decision on whether to implant a drug-eluting or bare-metal stent during percutaneous coronary intervention (PCI) depends in part on the perceived likelihood of the patient developing late stent thrombosis. Noncardiac surgery and bleeding are associated with discontinuation of dual antiplatelet therapy and with increased stent thrombosis. We assessed the incidence of and predictors for subsequent noncardiac surgery and bleeding episodes in patients who had undergone PCI. Methods and Results—Hospital discharge coding data were used to identify all adult patients undergoing public hospital PCI in New Zealand from 1996 to 2001. Hospital admissions during the ensuing 5 years were analyzed for noncardiac surgery and bleeding episodes. Eleven thousand one hundred fifty-one patients (age, 62±11 years; 30% women) underwent PCI, mainly for an acute coronary syndrome (73%). During the 5-year follow-up, 26% of the population underwent at least 1 noncardiac surgical procedure (23% orthopedic, 20% abdominal, 12% urologic, 10% vascular, 35% others) and 8.6% had at least 1 bleeding episode either requiring or occurring during hospitalization. Of those, half were gastrointestinal, and one quarter of bleeding events required blood transfusion. The main clinical predictors of noncardiac surgery were advanced age, previous noncardiac surgery, osteoarthritis, and peripheral vascular disease. A previous bleeding admission and age were the strongest predictors of subsequent bleeding. Conclusions—Noncardiac surgery is required frequently after PCI, whereas bleeding is less common. Before implanting a drug-eluting or bare-metal stent, individual patient risk stratification by the interventional cardiologist should include assessment of whether there is an increased likelihood of needing noncardiac surgery or developing bleeding.

Elevated B-type natriuretic peptide despite normal left ventricular function on rest and exercise stress echocardiography in mitral regurgitation.

AIMS To determine whether elevated B-type natriuretic peptide (BNP) predicts left ventricular (LV) contractile dysfunction on exercise stress echocardiography in patients with severe mitral regurgitation (MR). METHODS AND RESULTS Thirty three patients with moderate-to-severe or severe MR, a LV ejection fraction > or =60% and New York Heart Association Class I or II symptoms, and 12 controls underwent resting and exercise stress echocardiography. In 20 MR patients, BNP was within the normal range (mean +/- SD, 7.7 +/- 2.7 pmol/L), and in 13 MR patients, BNP was >12 pmol/L (19.6 +/- 7.6 pmol/L). LV end-systolic volume index after exercise was lower in controls than patients with MR (P < 0.0001), but similar in MR patients with normal and elevated BNP, respectively (controls 8.5 +/- 3.9, MR 20 +/- 7 vs. 20 +/- 9 cm(2)/m(2), P > 0.05). However, pulmonary artery systolic pressure (PAP) after exercise was higher in MR with high BNP (70 +/- 20 vs. 48 +/- 11 mmHg, <0.0001) and controls (38+/-11 mmHg). A two-fold increase in plasma BNP was associated with an average increase in resting PAP of 7.6 (95% CI 2.9, 12.2) mmHg, an increase in post-exercise PAP of 14.4 (95% CI 9.0, 19.9) mmHg and increase in left atrial area index of 2.1 (95% CI 0.5, 3.8) cm(2)/m(2). However, there was no significant association between the plasma level of BNP and any rest or post-exercise measure of LV systolic function (r < 0.25, P > 0.05 for all). CONCLUSION The plasma level of BNP may be within the normal range in patients with moderate-to-severe or severe MR despite significant increases in LV end-systolic volume. Increase in BNP is associated with pulmonary artery hypertension on exercise and left atrial enlargement even when LV systolic function on exercise stress echocardiography is normal.

B-type natriuretic peptide and left ventricular dysfunction on exercise echocardiography in patients with chronic aortic regurgitation

Objective: To determine whether plasma levels of B-type natriuretic peptide (BNP) predict left ventricular (LV) dysfunction on exercise echocardiography in patients with moderate to severe aortic regurgitation (AR). Design: Case–control study. Setting: Outpatient cardiology departments. Patients: 39 asymptomatic or mildly symptomatic patients with chronic moderate to severe AR and a normal LV ejection fraction (>50%), and 10 normal controls. Main outcome measures: Plasma level of BNP and echocardiographic measures of LV function at rest and immediately after treadmill exercise. Results: LV end systolic volume index (LVESVI) was significantly increased in AR patients with normal BNP (⩽12 pmol/l) compared with controls (mean (SD) 32 (13) vs 17 (7) ml/m2, p = 0.002) but was similar for AR patients with normal and elevated BNP (38 (16), p = 0.14). In AR patients there was no association between plasma BNP and measures of LV function on echocardiography at rest (r<0.30, p>0.05 for all). However, there were modest but statistically significant associations between the plasma level of BNP and severity of AR indicated by a greater AR:LV outflow tract width ratio (r = 0.37, p = 0.02) and lower diastolic blood pressure (r = −0.44, p = 0.004). Increased BNP was also associated with a greater LVESVI (r = 0.33, p = 0.04) and lower LV longitudinal strain rate (r = −0.037, 0.02) on echocardiography after exercise. Conclusions: In moderate to severe AR compensatory LV remodelling can occur with no increase in plasma BNP. Increased BNP is associated with more severe regurgitation and changes consistent with early LV dysfunction on exercise echocardiography.

Pilot Study to Assess the Influence of β-Blockade on Mitral Regurgitant Volume and Left Ventricular Work in Degenerative Mitral Valve Disease

Background— A medical treatment that decreases the likelihood of left ventricular (LV) dysfunction or symptoms would benefit patients with moderate to severe degenerative mitral regurgitation. The aim of this pilot study was to determine the short-term effects of a &bgr;-blocker on mitral regurgitant volume and LV work in these patients. Methods and Results— Twenty-five patients with moderate or severe degenerative mitral regurgitation were randomized in a double-blind crossover study to the &bgr;1-selective adrenergic blocker metoprolol (mean daily dose, 119 mg; range 23.75 to 190 mg) and placebo for 14±3 days. At the end of each treatment period, ascending aortic flow and LV stroke volume were measured by cardiac magnetic resonance imaging, and mitral regurgitant volume was calculated. On &bgr;-blocker, heart rate decreased from 65±10 by 10±7 bpm (mean±SD) and systolic blood pressure decreased from 138±18 by 16±12 mm Hg (P<0.0001 for both). No significant change occurred in LV ejection fraction (from 65±5%; change, −0.6±2.7%; P=0.3) or mitral regurgitant volume (from 59±36 mL; change, 3±13 mL; P=0.3), but forward stroke volume increased from 89±21 by 5±11 mL (P=0.03). Because heart rate was lower on metoprolol, cardiac output decreased from 5.68±1.04 by 0.56±0.78 L/min (P=0.001), but a greater decrease occurred in LV output, from 9.51±2.22 by 1.30±1.08 L/min (P<0.0001). Mitral regurgitant volume per minute decreased from 3.83±2.41 by 0.74±1.00 L/min (P=0.001). The decrease in LV work on &bgr;-blocker (mean, 21%; 95% confidence interval, 15 to 27) was greater (P=0.001) than the decrease in cardiac output (mean, 9%; 95% confidence interval, 3 to 15). Conclusions— In this pilot study, short-term treatment with a &bgr;-blocker did not change mitral regurgitant volume per beat but decreased LV work in patients with moderate to severe degenerative mitral regurgitation. Further research is needed to determine whether longer-term treatment with &bgr;-blockers will decrease progressive LV dysfunction and symptomatic deterioration.

Eosinophilia and Coronary Artery Vasospasm

OBJECTIVE To describe the clinical features, natural history and response to treatment of coronary vasospasm associated with eosinophilia. METHODS Two patients with eosinophilia who had recurrent acute coronary events due to multi-vessel coronary artery spasm are described. The clinical presentation and outcomes of these 2 patients and 17 additional cases of eosinophilia and coronary artery vasospasm identified on a systematic literature review are presented. RESULTS Patients were usually admitted because of repeated episodes of angina at rest and raised plasma markers of myocyte necrosis. Dynamic ST elevation was observed in 15 (83%) patients. Coronary angiography was performed in all patients. Spontaneous (n=7) or provoked (n=8) coronary artery spasm, which was usually multi-focal, was observed in 15 (83%) patients. Symptoms often continued despite high dose vasodilators but responded well to prednisone. Recurrent coronary events were frequent, and included sudden death (n=4), resuscitated cardiac arrest (n=2), myocardial infarction (n=10) and unstable angina (n=11). Recurrent events were more frequent when not taking compared to when taking prednisone (4.2 versus 0.4 events/year, p=0.002, hazard ratio 11, 95% confidence interval 2.4-50). CONCLUSION Published case reports suggest that coronary vasospasm associated with eosinophilia responds poorly to conventional vasodilator treatment and the risk of recurrent coronary events is high. Most patients respond to treatment which suppresses the eosinophilia.

Comparison of Atrial and Brain Natriuretic Peptide for the Assessment of Mitral Stenosis

BACKGROUND Accurate evaluation of the functional consequences of mitral stenosis (MS) can be difficult. The aim of this study was to evaluate the relationship between both atrial (ANP) and brain natriuretic peptides (BNP) and symptoms, exercise capacity and echocardiographic measures of MS severity. METHODS Thirty patients with moderate to severe MS and 14 normal controls underwent clinical assessment, exercise stress echocardiography, measurement of ANP and BNP and two years follow up for clinical events. RESULTS BNP was higher in MS patients than controls (BNP 58 [IQR 34, 93] vs. 16 [14, 25], p < 0.0001). There was considerable overlap in exercise capacity and echocardiographic severity between asymptomatic and symptomatic patients. An increase in BNP was associated with a larger left atrial area index (r = 0.67, p < 0.0001), reduced mitral valve area (r = -0.38, p = 0.05) and higher resting pulmonary artery pressure (r = 0.47, p = 0.008). Increased BNP predicted lower treadmill exercise capacity (AUC = 0.82 [95% confidence interval 0.67, 0.97], p = 0.004), guideline criteria for intervention (AUC = 0.87 [0.74, 0.99], p = 0.006) and adverse events during follow up (AUC = 0.81 [0.64, 0.99], p = 0.03). Associations for ANP in general were similar but slightly weaker, and ANP did not provide additional predictive information to BNP. CONCLUSION BNP may improve risk stratification of patients with MS, particularly when symptoms are equivocal.