- Email: [email protected]
Value of right ventricular strain in predicting functional capacity in patients with mitral stenosis
Letters to the Editor
Another interesting aspect observed in our study was that there is a difference of the detected arrhythmias between Cardiophone and Holter ECG. Cardiophone detected more often PAF/PAFL. On the other hand, Holter ECG detected PAF/PAFL only 11% but about 30% of PAC and PVC. We speculate that this may be due to the higher incidence of palpitation in PAF/PAFL than PSVT patients. (1/18 days vs. 1/27 days in our study) Since the average rental period was 27 ± 32 days, a longer rental period may increase diagnosis of PSVT. About 50% of patients with palpitations presented with confirmed arrhythmia. There were also many cases of patients in sinus rhythm when palpitations occurred. The rate of coincidence with final diagnosis was superior in Cardiophone than that of Holter ECG. The combination of each test may increase the diagnostic value of patients with palpitations We are grateful to Vincent Ventimiglia for his linguistic advice.
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References [1] Kroenke K, Arrington ME, Mangelsdorff AD. The prevalence of symptoms in medical outpatients and the adequacy of therapy. Arch Intern Med 1990;150:1685–9. [2] Pritchett EL. Management of atrial fibrillation. N Engl J Med 1992;326:1264–71. [3] Antman E, Dimarco J, Domanski MJ, et al. Atrial-fibrillation - current understandings and research imperatives. J Am Coll Cardiol 1993;22:1830–4. [4] Shimada M, Akaishi M, Asakura K, et al. Usefulness of the newly developed transtelephonic electrocardiogram and computer-supported response system. J Cardiol 1996;27:211–7. [5] Weber BE, Kapoor WN. Evaluation and outcomes of patients with palpitations. Am J Med 1996;100:138–48. [6] Zimetbaum PJ, Josephson ME. The evolving role of ambulatory arrhythmia monitoring in general clinical practice. Ann Intern Med 1999;130:848–56. [7] Krahn AD, Klein GJ, Skanes AC, Yee R. Insertable loop recorder use for detection of intermittent arrhythmias. Pace 2004;27:657–64. [8] Zimetbaum PJ, Kim KY, Josephson ME, Goldberger AL, Cohen DJ. Diagnostic yield and optimal duration of continuous-loop event monitoring for the diagnosis of palpitations. A cost-effectiveness analysis. Ann Intern Med 1998;128:890–5.
0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.03.182
Value of right ventricular strain in predicting functional capacity in patients with mitral stenosis Marildes L. Castro a, Marcia M. Barbosa b, José Augusto A. Barbosa b, Fernanda Rodrigues de Almeida a, William Antônio de Magalhães Esteves a, Timothy C. Tan c, Maria Carmo P. Nunes a,c,⁎ a b c
Post-Graduate Program in Infectious Diseases and Tropical Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil Ecocenter, Hospital Socor, Belo Horizonte, MG, Brazil Cardiac Ultrasound Lab, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
a r t i c l e
i n f o
Article history: Received 22 January 2013 Accepted 31 March 2013 Available online 4 May 2013 Keywords: Mitral stenosis Right ventricular function Right ventricular strain Functional capacity
Rheumatic heart disease remains a major health problem, particularly in developing countries where it causes significant cardiovascular morbidity and mortality in young people [1]. Mitral stenosis (MS) is the predominant form of valve involvement in rheumatic disease, which usually produces pulmonary hypertension and consequently an increase in right ventricular (RV) afterload [2]. Although the hemodynamic consequences of MS affect the RV as mediated by pulmonary hypertension, the pathophysiologic mechanisms of RV dysfunction are not well defined. Some studies have shown dissociation between pulmonary artery pressures and RV function [3,4]. Several factors may contribute to clinical presentation in MS and symptoms may be inconsistent with the standard measurements of MS severity [5]. Although pulmonary hypertension is considered to be a major determinant of exercise capacity in MS, the value of RV function in predicting effort tolerance is not well established. This study aims to ⁎ Corresponding author at: Departamento de Clínica Médica—UFMG, Av Professor Alfredo Balena, 190, Santa Efigênia, 30130 100 Belo Horizonte, MG, Brazil. Tel.: +55 31 34099746; fax: +55 31 34099437. E-mail address: [email protected] (M.C.P. Nunes).
assess RV function in patients with pure severe rheumatic MS using conventional and emerging echocardiographic techniques, and also to determine if RV strain as parameter of RV function is associated with functional capacity in this setting. Consecutive patients referred for management of rheumatic valve disease, were recruited prospectively from a tertiary referral center for heart valve disease. Exclusion criteria included any comorbid conditions which may independently affect RV function including chronic obstructive pulmonary disease, hemodynamically significant non-mitral valvular disease, and congenital heart disease. Patients with atrial fibrillation were also excluded. Twenty-seven age and gender healthy subjects, with normal standard echocardiograms and good quality images were selected as controls. Doppler echocardiogram with color flow mapping and tissue Doppler imaging was performed in all patients using commercially available hardware and software (Vivid 7; GE Vingmed Ultrasound AS, Horten, Norway). Left ventricular (LV) and RV measurements were made according to the recommendations of the American Society of Echocardiography [6]. The ejection fraction was calculated using the Simpson biplane method. Mitral valve area was obtained by planimetry and concurrently calculated using the pressure half-time method. Peak and mean transmitral diastolic pressure gradients were measured from Doppler profiles recorded in the apical four-chamber view. The continuous-wave Doppler tricuspid regurgitant velocity was used to determine systolic pulmonary artery pressure (SPAP) using the simplified Bernoulli equation. Left atrial volume (LAV) was obtained by the biplane area–length method in the apical 4 and 2-chamber views. End-diastolic area of the RV cavity was measured from the apical four-chamber view. Tricuspid annular plane systolic excursion (TAPSE) was determined in the apical four-chamber view, with the M-mode cursor placed through the lateral tricuspid annulus and the maximal systolic displacement
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Letters to the Editor
Fig. 1. Colored Doppler tissue image of RV shows the strain curve recorded within the basal segment of the RV free wall (A) and two-dimensional strain imaging showing RV longitudinal strain.
measured [7]. RV myocardial performance index was calculated as the ratio between total RV isovolumic time (contraction and relaxation) divided by pulmonary ejection time [8]. Peak systolic (S), early, and late diastolic tissue Doppler velocities were acquired at the tricuspid annulus [8]. Doppler-based strain and strain rate were obtained by placing a 10-mm sample volume in the RV at its basal free wall in the apical 4-chamber view [9] (Fig. 1A). To determine the RV two-dimensional (2D) longitudinal strain, the endocardial border of the RV was traced manually and tracked by the software (GE EchoPAC) offline. The RV free wall and interventricular septum were divided in three segments, basal, mid, and apical, for quantification of regional systolic strain. Global longitudinal RV strain was calculated by averaging strain values measured for all 6 segments [9,10] (Fig. 1B). Measurements were made by a single cardiologist (MMB) in three cardiac cycles, and the average was used for statistical analyses. Intraobserver variability in RV Doppler-based strain and 2D longitudinal strain was calculated in a sample of 20 randomly selected individuals. For the analyses of variability, we calculated an adjusted coefficient of variation, defined as the ratio of the standard deviation and the mean absolute readings and intra-class correlation coefficient for RV Doppler-based strain and RV 2D longitudinal strain. The Kolmogorov–Smirnov analysis was used to classify the normality of the data in order to choose parametric vs. non-parametric tests. The Student's t-test was used for comparisons between groups for variables with normal distribution, and the Mann–Whitney test was used for nonGaussian distribution. Pearson's correlation coefficients were calculated to determine correlations between variables. Logistic regression was used to identify the variables associated with worse functional class (NYHA class III–IV). To explore potential predictors of low functional capacity, univariate and multivariate analyses of clinical and echocardiographic characteristics were performed. A significance level of 5% was considered in all statistical tests. Analyses were performed using the Statistical Package for Social Sciences version 18.0 (SPSS Inc., Chicago, IL, USA). Forty-six patients and 27 healthy individuals were selected. Table 1 displays the clinical and echocardiographic data in both groups. Eighteen patients (39%) were asymptomatic while the remaining 28 patients (61%) had exertional dyspnea. The mean mitral valve area by planimetry was 1.1 ± 0.3 cm2, peak gradient was 19.2 ± 7.9 mm Hg, mean gradient was 11.2 ± 5.8 mm Hg, and pulmonary systolic artery pressure was 46.6 ± 13.9 mm Hg. There was no significant difference in LV diameters and ejection fraction between patients and controls (Table 1). All echocardiographic
measures used to assess RV function, with the exception of RV enddiastolic area, were reduced in cases compared to controls. The mean RV 2D global longitudinal strain (GLS) was significantly lower in patients compared to healthy subjects (− 17.5 ± 3.9% vs. − 21.8 ± 3.4%; p = 0.007). Among the classic echocardiographic markers of hemodynamic severity of MS, including mitral valve area, pressure gradients and systolic pulmonary artery pressure, only pulmonary pressure was correlated with RV 2D longitudinal strain (Fig. 2). When we stratify the patients based on NYHA functional class, patients with MS in functional class III–IV had significantly reduced RV 2D global longitudinal strain compared with patients in class I–II (− 14.7 ± 2.3% vs. 18.7 ± 3.7%; p = 0.004). The determinants of functional capacity assessed by NYHA class are shown in Table 2. By multivariate analysis, peak transvalvular gradient, and RV 2D longitudinal strain were identified as the most significant predictors of poor functional status. Intra-observer variabilities of RV Doppler-based strain and RV 2D global longitudinal strain were 6.3% and 6.5%, respectively. Using intra-class correlation coefficient, the variabilities were 0.89 and 0.92, respectively.
Table 1 Clinical and echocardiographic features of the patients and controls. Variablesa
Patients
Controls
p-value
Age (years) Female (n/%) Body surface area (m2) LV end-diastolic diameter (mm) LV end-systolic diameter (mm) Left ventricular ejection fraction (%) Right atrium (cm2) Left atrium dimension (mm) Left atrium indexed volume (mL/m2) RV end-diastolic area (cm2) RV myocardial performance index Tricuspid annular motion (mm) RV peak systolic velocity (cm/s) RV peak early diastolic velocity (cm/s) RV peak late diastolic velocity (cm/s) RV Doppler-based strainb (−%) RV strain rate (1/s) RV 2D-longitudinal strain (−%) SPAP (mm Hg)
42.1 ± 10.6 42 (93) 1.70 ± 0.2 46.3 ± 4.6 29.5 ± 3.6 66.1 ± 5.7 13.4 ± 4.1 47.2 ± 5.7 51.6 ± 15.6 11.5 ± 4.5 0.37 ± 0.12 22.1 ± 3.8 11.6 ± 2.3 12.5 ± 2.9 15.1 ± 5.2 25.2 ± 6.2 1.4 [1.2/2.0] 17.5 ± 3.9 46.6 ± 13.3
38.4 ± 8.5 23 (85) 1.66 ± 0.2 46.2 ± 3.8 28.9 ± 3.9 67.4 ± 6.1 11.1 ± 4.4 32.4 ± 4.2 22.8 ± 6.3 10.8 ± 3.5 0.22 ± 0.19 24.1 ± 2.4 14.2 ± 1.8 15.6 ± 2.9 12.5 ± 3.4 29.1 ± 6.4 1.7 [1.3/2.2] 21.8 ± 3.4 30.1 ± 2.3
0.126 0.259 0.374 0.912 0.557 0.362 0.093 b 0.001 b 0.001 0.679 0.006 0.072 b 0.001 b 0.001 0.021 0.015 0.069 0.007 b 0.001
LV = left ventricular; RV = right ventricular; SPAP = systolic pulmonary artery pressure. a Data are expressed as the mean value ± SD, median (inter-quartile range) or number (percentage) of patients. b Doppler based strain.
Letters to the Editor
Fig. 2. Correlation between RV 2D longitudinal strain and systolic pulmonary artery pressure.
This study compared several echocardiographic measures of RV function in patients with severe MS aimed to correlate RV function with functional capacity. Our results demonstrated that RV function, as measured by both conventional and more novel echocardiographic measures, was reduced in patients with MS compared to controls. RV strain was the only echocardiographic parameter that correlated with pulmonary artery pressure. Additionally, our results showed that RV strain remained an independent determinant of functional capacity, after adjusting for pulmonary artery pressure and transmitral gradient. Previous studies have assessed RV function in MS, but these studies have been small studies with several limitations and reported conflicting results. The study by Mittal et al. [4] did not find any relationship between parameters of RV function and pulmonary artery pressure in 22 patients with MS. The authors attributed the impairment of RV systolic function to myocardial involvement of the rheumatic process. The study by Ozdemir et al. [11] demonstrated that patients with MS had reduced RV 2D longitudinal strain. However, this study only included patients with mildto-moderate MS with a mean mitral valve area of 1.9 ± 0.6 cm2 who only had mildly increased pulmonary artery pressures. Similarly, the study by Tanboga et al. [12] which only included patients with non-severe MS, also found lower RV 2D longitudinal strain in MS patients compared to controls, but did not find any correlation between the RV strain and pulmonary pressures. On the contrary, the study by Wroblewski et al. [3] showed normal RV size and function in a small cohort of patients (8 patients) with MS and moderate pulmonary hypertension but this study was limited by the small sample size and the methodology used to assess RV ejection fraction. In our study we evaluated RV function using both conventional and more novel echocardiographic parameters in patients with severe MS. Table 2 Determinants factors of functional capacity in mitral stenosis patients. Covariates
Odds ratio
(95% CI)
p value
Univariate analysis SPAP (mm Hg) Transmitral peak gradient (mm Hg) MV area (cm2) RV longitudinal 2D strain (−%) RV Doppler based strain (−%) RV peak systolic velocity (cm/s) Tricuspid annular motion (mm)
1.070 1.110 0.158 0.613 0.830 0.806 0.789
1.016–1.127 1.008–1.223 0.013–1.920 0.418–0.898 0.705–0.978 0.607–1.071 0.613–1.015
0.010 0.034 0.148 0.012 0.026 0.137 0.066
Multivariate analysis Transmitral peak gradient (mm Hg) RV longitudinal 2D strain (−%)
1.275 0.542
1.005–1.618 0.293–0.987
0.045 0.046
LV = left ventricular; RV = right ventricular; SPAP = systolic pulmonary artery pressure.
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The use of these new echocardiographic methods, including myocardial deformation indices, may be able to provide more accurate and quantitative measures of RV function. Our results demonstrated a weak correlation between RV strain and pulmonary artery pressure, which implies that RV function can be affected by other mechanisms besides RV afterload, such as by direct myocardial involvement of rheumatic processes. RV dysfunction has been reported in all cases of rheumatic MS regardless of pulmonary artery pressure [13] and that right heart disease may progress independent of the MS [14]. Overall, the echocardiographic parameters of RV function as assessed using Tissue Doppler imaging, Doppler-based strain, and 2D longitudinal strain were reduced in the MS patients compared to controls at rest, even though the collective mean values of these echocardiographic measures remained within the normal range. In the context of MS, the RV appears to activate mechanisms of adaptation that enable it to maintain a normal function at rest. However, during exercise the patients who had low RV strain had greater intolerance to exercise compared with those with normal RV strain, independent of the severity of MS. Although very promising, quantification of myocardial deformation indices in this context appears promising, there are still limitations [15]. RV strain values are influenced by loading conditions, RV size and stroke volume. Feasibility of strain measurement may also pose a problem given the thin RV wall. Additionally normal values for different age ranges, body size, and gender have yet to be established. Therefore, tissue Doppler imaging and speckle tracking at this point may not be suitable for widespread use in the clinical setting. In conclusion, this study demonstrated that echocardiographic variables to assess RV function were reduced in patients with MS compared to controls. RV longitudinal strain was associated independently with functional class, after adjusting for pulmonary artery pressure and transmitral gradient. Measurement of RV strain might provide important information about the exercise tolerance of patients with MS. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
References [1] Marijon E, Mirabel M, Celermajer DS, Jouven X. Rheumatic heart disease. Lancet 2012;379:953–64. [2] Remenyi B, Wilson N, Steer A, et al. World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease—an evidence-based guideline. Nat Rev Cardiol 2012;9:297–309. [3] Wroblewski E, James F, Spann JF, Bove AA. Right ventricular performance in mitral stenosis. Am J Cardiol 1981;47:51–5. [4] Mittal SR, Goozar RS. Echocardiographic evaluation of right ventricular systolic functions in pure mitral stenosis. Int J Cardiovasc Imaging 2001;17:13–8. [5] Hugenholtz PG, Ryan TJ, Stein SW, Abelmann WH. The spectrum of pure mitral stenosis. Hemodynamic studies in relation to clinical disability. Am J Cardiol 1962;10:773–84. [6] Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440–63. [7] Saxena N, Rajagopalan N, Edelman K, Lopez-Candales A. Tricuspid annular systolic velocity: a useful measurement in determining right ventricular systolic function regardless of pulmonary artery pressures. Echocardiography 2006;23:750–5. [8] Lindqvist P, Calcutteea A, Henein M. Echocardiography in the assessment of right heart function. Eur J Echocardiogr 2008;9:225–34. [9] Horton KD, Meece RW, Hill JC. Assessment of the right ventricle by echocardiography: a primer for cardiac sonographers. J Am Soc Echocardiogr 2009;22:776–92 [quiz 861–2]. [10] Amundsen BH, Helle-Valle T, Edvardsen T, et al. Noninvasive myocardial strain measurement by speckle tracking echocardiography: validation against sonomicrometry and tagged magnetic resonance imaging. J Am Coll Cardiol 2006;47:789–93. [11] Ozdemir AO, Kaya CT, Ozdol C, et al. Two-dimensional longitudinal strain and strain rate imaging for assessing the right ventricular function in patients with mitral stenosis. Echocardiography 2010;27:525–33.
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[12] Tanboga IH, Kurt M, Bilen E, et al. Assessment of right ventricular mechanics in patients with mitral stenosis by two-dimensional deformation imaging. Echocardiography 2012;29:956–61. [13] Pande S, Agarwal SK, Dhir U, Chaudhary A, Kumar S, Agarwal V. Pulmonary arterial hypertension in rheumatic mitral stenosis: does it affect right ventricular function and outcome after mitral valve replacement? Interact Cardiovasc Thorac Surg 2009;9:421–5.
[14] Sagie A, Freitas N, Padial LR, et al. Doppler echocardiographic assessment of long-term progression of mitral stenosis in 103 patients: valve area and right heart disease. J Am Coll Cardiol 1996;28:472–9. [15] Valsangiacomo Buechel ER, Mertens LL. Imaging the right heart: the use of integrated multimodality imaging. Eur Heart J 2012;33:949–60.
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Drug-eluting balloons for coronary artery disease: an updated meta-analysis of randomized controlled trials☆ Joey S.W. Kwong, Cheuk-Man Yu ⁎ Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, S.H. Ho Cardiovascular Disease and Stroke Centre, Heart Education And Research Training (HEART) Centre and Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong
a r t i c l e
i n f o
Article history: Received 23 January 2013 Accepted 31 March 2013 Available online 2 May 2013 Keywords: Drug-eluting balloon Coronary artery disease Systematic review Meta-analysis
Drug-eluting balloons (DEB) continue to present as a promising percutaneous intervention for the treatment of coronary artery disease (CAD) [1]. Since we performed our meta-analysis of five randomized trials enrolling 349 patients [2], several other studies evaluating DEB in CAD have been completed [3,4]. Therefore, we incorporated the new evidence into an updated meta-analysis to extend the current knowledge on the efficacy and safety of DEB in patients with CAD. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched in December 2012 for eligible randomized controlled trials (RCTs) evaluating DEB in adult patients (≥18 years) with CAD using the search terms “coated balloon” or “eluting balloon.” Studies were selected independently by the two authors, and disagreements were resolved by discussion. The primary clinical outcomes were (i) target lesion revascularization (TLR), (ii) major adverse cardiac events (MACE), (iii) mortality, (iv) myocardial infarction (MI), and (v) stent thrombosis. Secondary outcomes were in-stent and in-segment measurements of late lumen loss, minimal lumen diameter, and binary restenosis. A Mantel–Haenszel randomeffects model was used to calculate odd ratios (ORs) with their 95% confidence intervals (CIs) for dichotomous data; continuous data were analyzed using an inverse variance random-effects model, and mean differences (MDs) with 95% CIs were calculated. Main analyses were conducted using data of the longest follow-up period, and sensitivity analysis exploring the impact of follow-up duration was also pursued. To detect the effect of the inclusion of small studies, a
☆ The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ⁎ Corresponding author. Tel.: +852 2632 3127; fax: +852 2645 1699. E-mail address: [email protected] (C.-M. Yu).
sensitivity analysis with the fixed-effect model was also performed. Results were considered to be statistically significant at P b 0.05. Statistical heterogeneity was assessed using the chi-squared test and I2 statistic; I2 values of ≥25%, ≥50%, and ≥75% were categorized as low, moderate, and high heterogeneity, respectively (P b 0.10 for statistical significance). Statistical analysis was performed using the Review Manager 5.2 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). Of the 5042 titles and abstracts retrieved from our literature search, 42 full-text articles were obtained for further assessment, with one additional record identified from personal library. A total of seven studies enrolling 861 participants were eventually included in our meta-analysis, of whom 383 were randomized to DEB, 227 to DES, and 251 to POBA (Table 1) [3–8]. Only one study enrolled participants with de novo lesions (stable or unstable angina); the remaining six studies recruited patients with in-stent restenosis (ISR). Two studies compared DEB vs. DES, four compared DEB vs. POBA, and one study utilized a three-arm approach investigating DEB, DES, and POBA. All the balloon systems used in the included studies were coated with paclitaxel (SeQuent® Please, 4 trials; Paccocath®, 2 trials, Dior®, 1 trial), and all the DES comparison groups used the paclitaxel-eluting Taxus® Liberté® device. Angiographic observations were obtained at 6 to 8 months, with clinical follow-up ranging from 6 months to 5 years. Compared to DES, DEB showed no significant effects in any of the clinical outcomes amongst the overall CAD populations (TLR: OR = 1.38, 95% CI = 0.41–4.72, P = 0.60; MACE: OR = 1.18, 95% CI = 0.43–3.22 P = 0.75; mortality: OR = 0.58, 95% CI = 0.20–1.63, P = 0.30; MI: OR = 0.97, 95% CI = 0.26–3.65, P = 0.97; stent thrombosis: OR = 0.96, 95% CI = 0.06–15.44, P = 0.97) or participants with ISR (TLR: OR = 0.89, 95% CI = 0.17–4.52, P =0.88; MACE: OR = 0.80, 95% CI = 0.26–2.46, P = 0.69; mortality: OR = 0.53, 95% CI = 0.17–1.60, P = 0.26; MI: OR = 0.77, 95% CI = 0.18–3.26, P = 0.72; stent thrombosis: OR = 0.96, 95% CI = 0.06–15.44, P = 0.97). In-stent angiographic observations were reported in only one (PEPCAD II) of the two studies comparing DEB to DES in participants with ISR, and thus meta-analyses were inconclusive. For in-segment measures, no significant differences were observed in the meta-analyses of LLL (MD = − 0.26, 95% CI = − 0.45 to − 0.07, P = 0.48), MLD (MD = 0.01, 95% CI = − 0.14 to 0.15, P = 0.94) or binary restenosis (OR = 0.63, 95% CI = 0.17–2.42, P = 0.50). Participants in the five DEB vs. POBA arms all had ISR. Compared to POBA, treatment of DEB was associated with a significant reduction of TLR
Another interesting aspect observed in our study was that there is a difference of the detected arrhythmias between Cardiophone and Holter ECG. Cardiophone detected more often PAF/PAFL. On the other hand, Holter ECG detected PAF/PAFL only 11% but about 30% of PAC and PVC. We speculate that this may be due to the higher incidence of palpitation in PAF/PAFL than PSVT patients. (1/18 days vs. 1/27 days in our study) Since the average rental period was 27 ± 32 days, a longer rental period may increase diagnosis of PSVT. About 50% of patients with palpitations presented with confirmed arrhythmia. There were also many cases of patients in sinus rhythm when palpitations occurred. The rate of coincidence with final diagnosis was superior in Cardiophone than that of Holter ECG. The combination of each test may increase the diagnostic value of patients with palpitations We are grateful to Vincent Ventimiglia for his linguistic advice.
2927
References [1] Kroenke K, Arrington ME, Mangelsdorff AD. The prevalence of symptoms in medical outpatients and the adequacy of therapy. Arch Intern Med 1990;150:1685–9. [2] Pritchett EL. Management of atrial fibrillation. N Engl J Med 1992;326:1264–71. [3] Antman E, Dimarco J, Domanski MJ, et al. Atrial-fibrillation - current understandings and research imperatives. J Am Coll Cardiol 1993;22:1830–4. [4] Shimada M, Akaishi M, Asakura K, et al. Usefulness of the newly developed transtelephonic electrocardiogram and computer-supported response system. J Cardiol 1996;27:211–7. [5] Weber BE, Kapoor WN. Evaluation and outcomes of patients with palpitations. Am J Med 1996;100:138–48. [6] Zimetbaum PJ, Josephson ME. The evolving role of ambulatory arrhythmia monitoring in general clinical practice. Ann Intern Med 1999;130:848–56. [7] Krahn AD, Klein GJ, Skanes AC, Yee R. Insertable loop recorder use for detection of intermittent arrhythmias. Pace 2004;27:657–64. [8] Zimetbaum PJ, Kim KY, Josephson ME, Goldberger AL, Cohen DJ. Diagnostic yield and optimal duration of continuous-loop event monitoring for the diagnosis of palpitations. A cost-effectiveness analysis. Ann Intern Med 1998;128:890–5.
0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.03.182
Value of right ventricular strain in predicting functional capacity in patients with mitral stenosis Marildes L. Castro a, Marcia M. Barbosa b, José Augusto A. Barbosa b, Fernanda Rodrigues de Almeida a, William Antônio de Magalhães Esteves a, Timothy C. Tan c, Maria Carmo P. Nunes a,c,⁎ a b c
Post-Graduate Program in Infectious Diseases and Tropical Medicine, School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil Ecocenter, Hospital Socor, Belo Horizonte, MG, Brazil Cardiac Ultrasound Lab, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
a r t i c l e
i n f o
Article history: Received 22 January 2013 Accepted 31 March 2013 Available online 4 May 2013 Keywords: Mitral stenosis Right ventricular function Right ventricular strain Functional capacity
Rheumatic heart disease remains a major health problem, particularly in developing countries where it causes significant cardiovascular morbidity and mortality in young people [1]. Mitral stenosis (MS) is the predominant form of valve involvement in rheumatic disease, which usually produces pulmonary hypertension and consequently an increase in right ventricular (RV) afterload [2]. Although the hemodynamic consequences of MS affect the RV as mediated by pulmonary hypertension, the pathophysiologic mechanisms of RV dysfunction are not well defined. Some studies have shown dissociation between pulmonary artery pressures and RV function [3,4]. Several factors may contribute to clinical presentation in MS and symptoms may be inconsistent with the standard measurements of MS severity [5]. Although pulmonary hypertension is considered to be a major determinant of exercise capacity in MS, the value of RV function in predicting effort tolerance is not well established. This study aims to ⁎ Corresponding author at: Departamento de Clínica Médica—UFMG, Av Professor Alfredo Balena, 190, Santa Efigênia, 30130 100 Belo Horizonte, MG, Brazil. Tel.: +55 31 34099746; fax: +55 31 34099437. E-mail address: [email protected] (M.C.P. Nunes).
assess RV function in patients with pure severe rheumatic MS using conventional and emerging echocardiographic techniques, and also to determine if RV strain as parameter of RV function is associated with functional capacity in this setting. Consecutive patients referred for management of rheumatic valve disease, were recruited prospectively from a tertiary referral center for heart valve disease. Exclusion criteria included any comorbid conditions which may independently affect RV function including chronic obstructive pulmonary disease, hemodynamically significant non-mitral valvular disease, and congenital heart disease. Patients with atrial fibrillation were also excluded. Twenty-seven age and gender healthy subjects, with normal standard echocardiograms and good quality images were selected as controls. Doppler echocardiogram with color flow mapping and tissue Doppler imaging was performed in all patients using commercially available hardware and software (Vivid 7; GE Vingmed Ultrasound AS, Horten, Norway). Left ventricular (LV) and RV measurements were made according to the recommendations of the American Society of Echocardiography [6]. The ejection fraction was calculated using the Simpson biplane method. Mitral valve area was obtained by planimetry and concurrently calculated using the pressure half-time method. Peak and mean transmitral diastolic pressure gradients were measured from Doppler profiles recorded in the apical four-chamber view. The continuous-wave Doppler tricuspid regurgitant velocity was used to determine systolic pulmonary artery pressure (SPAP) using the simplified Bernoulli equation. Left atrial volume (LAV) was obtained by the biplane area–length method in the apical 4 and 2-chamber views. End-diastolic area of the RV cavity was measured from the apical four-chamber view. Tricuspid annular plane systolic excursion (TAPSE) was determined in the apical four-chamber view, with the M-mode cursor placed through the lateral tricuspid annulus and the maximal systolic displacement
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Letters to the Editor
Fig. 1. Colored Doppler tissue image of RV shows the strain curve recorded within the basal segment of the RV free wall (A) and two-dimensional strain imaging showing RV longitudinal strain.
measured [7]. RV myocardial performance index was calculated as the ratio between total RV isovolumic time (contraction and relaxation) divided by pulmonary ejection time [8]. Peak systolic (S), early, and late diastolic tissue Doppler velocities were acquired at the tricuspid annulus [8]. Doppler-based strain and strain rate were obtained by placing a 10-mm sample volume in the RV at its basal free wall in the apical 4-chamber view [9] (Fig. 1A). To determine the RV two-dimensional (2D) longitudinal strain, the endocardial border of the RV was traced manually and tracked by the software (GE EchoPAC) offline. The RV free wall and interventricular septum were divided in three segments, basal, mid, and apical, for quantification of regional systolic strain. Global longitudinal RV strain was calculated by averaging strain values measured for all 6 segments [9,10] (Fig. 1B). Measurements were made by a single cardiologist (MMB) in three cardiac cycles, and the average was used for statistical analyses. Intraobserver variability in RV Doppler-based strain and 2D longitudinal strain was calculated in a sample of 20 randomly selected individuals. For the analyses of variability, we calculated an adjusted coefficient of variation, defined as the ratio of the standard deviation and the mean absolute readings and intra-class correlation coefficient for RV Doppler-based strain and RV 2D longitudinal strain. The Kolmogorov–Smirnov analysis was used to classify the normality of the data in order to choose parametric vs. non-parametric tests. The Student's t-test was used for comparisons between groups for variables with normal distribution, and the Mann–Whitney test was used for nonGaussian distribution. Pearson's correlation coefficients were calculated to determine correlations between variables. Logistic regression was used to identify the variables associated with worse functional class (NYHA class III–IV). To explore potential predictors of low functional capacity, univariate and multivariate analyses of clinical and echocardiographic characteristics were performed. A significance level of 5% was considered in all statistical tests. Analyses were performed using the Statistical Package for Social Sciences version 18.0 (SPSS Inc., Chicago, IL, USA). Forty-six patients and 27 healthy individuals were selected. Table 1 displays the clinical and echocardiographic data in both groups. Eighteen patients (39%) were asymptomatic while the remaining 28 patients (61%) had exertional dyspnea. The mean mitral valve area by planimetry was 1.1 ± 0.3 cm2, peak gradient was 19.2 ± 7.9 mm Hg, mean gradient was 11.2 ± 5.8 mm Hg, and pulmonary systolic artery pressure was 46.6 ± 13.9 mm Hg. There was no significant difference in LV diameters and ejection fraction between patients and controls (Table 1). All echocardiographic
measures used to assess RV function, with the exception of RV enddiastolic area, were reduced in cases compared to controls. The mean RV 2D global longitudinal strain (GLS) was significantly lower in patients compared to healthy subjects (− 17.5 ± 3.9% vs. − 21.8 ± 3.4%; p = 0.007). Among the classic echocardiographic markers of hemodynamic severity of MS, including mitral valve area, pressure gradients and systolic pulmonary artery pressure, only pulmonary pressure was correlated with RV 2D longitudinal strain (Fig. 2). When we stratify the patients based on NYHA functional class, patients with MS in functional class III–IV had significantly reduced RV 2D global longitudinal strain compared with patients in class I–II (− 14.7 ± 2.3% vs. 18.7 ± 3.7%; p = 0.004). The determinants of functional capacity assessed by NYHA class are shown in Table 2. By multivariate analysis, peak transvalvular gradient, and RV 2D longitudinal strain were identified as the most significant predictors of poor functional status. Intra-observer variabilities of RV Doppler-based strain and RV 2D global longitudinal strain were 6.3% and 6.5%, respectively. Using intra-class correlation coefficient, the variabilities were 0.89 and 0.92, respectively.
Table 1 Clinical and echocardiographic features of the patients and controls. Variablesa
Patients
Controls
p-value
Age (years) Female (n/%) Body surface area (m2) LV end-diastolic diameter (mm) LV end-systolic diameter (mm) Left ventricular ejection fraction (%) Right atrium (cm2) Left atrium dimension (mm) Left atrium indexed volume (mL/m2) RV end-diastolic area (cm2) RV myocardial performance index Tricuspid annular motion (mm) RV peak systolic velocity (cm/s) RV peak early diastolic velocity (cm/s) RV peak late diastolic velocity (cm/s) RV Doppler-based strainb (−%) RV strain rate (1/s) RV 2D-longitudinal strain (−%) SPAP (mm Hg)
42.1 ± 10.6 42 (93) 1.70 ± 0.2 46.3 ± 4.6 29.5 ± 3.6 66.1 ± 5.7 13.4 ± 4.1 47.2 ± 5.7 51.6 ± 15.6 11.5 ± 4.5 0.37 ± 0.12 22.1 ± 3.8 11.6 ± 2.3 12.5 ± 2.9 15.1 ± 5.2 25.2 ± 6.2 1.4 [1.2/2.0] 17.5 ± 3.9 46.6 ± 13.3
38.4 ± 8.5 23 (85) 1.66 ± 0.2 46.2 ± 3.8 28.9 ± 3.9 67.4 ± 6.1 11.1 ± 4.4 32.4 ± 4.2 22.8 ± 6.3 10.8 ± 3.5 0.22 ± 0.19 24.1 ± 2.4 14.2 ± 1.8 15.6 ± 2.9 12.5 ± 3.4 29.1 ± 6.4 1.7 [1.3/2.2] 21.8 ± 3.4 30.1 ± 2.3
0.126 0.259 0.374 0.912 0.557 0.362 0.093 b 0.001 b 0.001 0.679 0.006 0.072 b 0.001 b 0.001 0.021 0.015 0.069 0.007 b 0.001
LV = left ventricular; RV = right ventricular; SPAP = systolic pulmonary artery pressure. a Data are expressed as the mean value ± SD, median (inter-quartile range) or number (percentage) of patients. b Doppler based strain.
Letters to the Editor
Fig. 2. Correlation between RV 2D longitudinal strain and systolic pulmonary artery pressure.
This study compared several echocardiographic measures of RV function in patients with severe MS aimed to correlate RV function with functional capacity. Our results demonstrated that RV function, as measured by both conventional and more novel echocardiographic measures, was reduced in patients with MS compared to controls. RV strain was the only echocardiographic parameter that correlated with pulmonary artery pressure. Additionally, our results showed that RV strain remained an independent determinant of functional capacity, after adjusting for pulmonary artery pressure and transmitral gradient. Previous studies have assessed RV function in MS, but these studies have been small studies with several limitations and reported conflicting results. The study by Mittal et al. [4] did not find any relationship between parameters of RV function and pulmonary artery pressure in 22 patients with MS. The authors attributed the impairment of RV systolic function to myocardial involvement of the rheumatic process. The study by Ozdemir et al. [11] demonstrated that patients with MS had reduced RV 2D longitudinal strain. However, this study only included patients with mildto-moderate MS with a mean mitral valve area of 1.9 ± 0.6 cm2 who only had mildly increased pulmonary artery pressures. Similarly, the study by Tanboga et al. [12] which only included patients with non-severe MS, also found lower RV 2D longitudinal strain in MS patients compared to controls, but did not find any correlation between the RV strain and pulmonary pressures. On the contrary, the study by Wroblewski et al. [3] showed normal RV size and function in a small cohort of patients (8 patients) with MS and moderate pulmonary hypertension but this study was limited by the small sample size and the methodology used to assess RV ejection fraction. In our study we evaluated RV function using both conventional and more novel echocardiographic parameters in patients with severe MS. Table 2 Determinants factors of functional capacity in mitral stenosis patients. Covariates
Odds ratio
(95% CI)
p value
Univariate analysis SPAP (mm Hg) Transmitral peak gradient (mm Hg) MV area (cm2) RV longitudinal 2D strain (−%) RV Doppler based strain (−%) RV peak systolic velocity (cm/s) Tricuspid annular motion (mm)
1.070 1.110 0.158 0.613 0.830 0.806 0.789
1.016–1.127 1.008–1.223 0.013–1.920 0.418–0.898 0.705–0.978 0.607–1.071 0.613–1.015
0.010 0.034 0.148 0.012 0.026 0.137 0.066
Multivariate analysis Transmitral peak gradient (mm Hg) RV longitudinal 2D strain (−%)
1.275 0.542
1.005–1.618 0.293–0.987
0.045 0.046
LV = left ventricular; RV = right ventricular; SPAP = systolic pulmonary artery pressure.
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The use of these new echocardiographic methods, including myocardial deformation indices, may be able to provide more accurate and quantitative measures of RV function. Our results demonstrated a weak correlation between RV strain and pulmonary artery pressure, which implies that RV function can be affected by other mechanisms besides RV afterload, such as by direct myocardial involvement of rheumatic processes. RV dysfunction has been reported in all cases of rheumatic MS regardless of pulmonary artery pressure [13] and that right heart disease may progress independent of the MS [14]. Overall, the echocardiographic parameters of RV function as assessed using Tissue Doppler imaging, Doppler-based strain, and 2D longitudinal strain were reduced in the MS patients compared to controls at rest, even though the collective mean values of these echocardiographic measures remained within the normal range. In the context of MS, the RV appears to activate mechanisms of adaptation that enable it to maintain a normal function at rest. However, during exercise the patients who had low RV strain had greater intolerance to exercise compared with those with normal RV strain, independent of the severity of MS. Although very promising, quantification of myocardial deformation indices in this context appears promising, there are still limitations [15]. RV strain values are influenced by loading conditions, RV size and stroke volume. Feasibility of strain measurement may also pose a problem given the thin RV wall. Additionally normal values for different age ranges, body size, and gender have yet to be established. Therefore, tissue Doppler imaging and speckle tracking at this point may not be suitable for widespread use in the clinical setting. In conclusion, this study demonstrated that echocardiographic variables to assess RV function were reduced in patients with MS compared to controls. RV longitudinal strain was associated independently with functional class, after adjusting for pulmonary artery pressure and transmitral gradient. Measurement of RV strain might provide important information about the exercise tolerance of patients with MS. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
References [1] Marijon E, Mirabel M, Celermajer DS, Jouven X. Rheumatic heart disease. Lancet 2012;379:953–64. [2] Remenyi B, Wilson N, Steer A, et al. World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease—an evidence-based guideline. Nat Rev Cardiol 2012;9:297–309. [3] Wroblewski E, James F, Spann JF, Bove AA. Right ventricular performance in mitral stenosis. Am J Cardiol 1981;47:51–5. [4] Mittal SR, Goozar RS. Echocardiographic evaluation of right ventricular systolic functions in pure mitral stenosis. Int J Cardiovasc Imaging 2001;17:13–8. [5] Hugenholtz PG, Ryan TJ, Stein SW, Abelmann WH. The spectrum of pure mitral stenosis. Hemodynamic studies in relation to clinical disability. Am J Cardiol 1962;10:773–84. [6] Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440–63. [7] Saxena N, Rajagopalan N, Edelman K, Lopez-Candales A. Tricuspid annular systolic velocity: a useful measurement in determining right ventricular systolic function regardless of pulmonary artery pressures. Echocardiography 2006;23:750–5. [8] Lindqvist P, Calcutteea A, Henein M. Echocardiography in the assessment of right heart function. Eur J Echocardiogr 2008;9:225–34. [9] Horton KD, Meece RW, Hill JC. Assessment of the right ventricle by echocardiography: a primer for cardiac sonographers. J Am Soc Echocardiogr 2009;22:776–92 [quiz 861–2]. [10] Amundsen BH, Helle-Valle T, Edvardsen T, et al. Noninvasive myocardial strain measurement by speckle tracking echocardiography: validation against sonomicrometry and tagged magnetic resonance imaging. J Am Coll Cardiol 2006;47:789–93. [11] Ozdemir AO, Kaya CT, Ozdol C, et al. Two-dimensional longitudinal strain and strain rate imaging for assessing the right ventricular function in patients with mitral stenosis. Echocardiography 2010;27:525–33.
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[12] Tanboga IH, Kurt M, Bilen E, et al. Assessment of right ventricular mechanics in patients with mitral stenosis by two-dimensional deformation imaging. Echocardiography 2012;29:956–61. [13] Pande S, Agarwal SK, Dhir U, Chaudhary A, Kumar S, Agarwal V. Pulmonary arterial hypertension in rheumatic mitral stenosis: does it affect right ventricular function and outcome after mitral valve replacement? Interact Cardiovasc Thorac Surg 2009;9:421–5.
[14] Sagie A, Freitas N, Padial LR, et al. Doppler echocardiographic assessment of long-term progression of mitral stenosis in 103 patients: valve area and right heart disease. J Am Coll Cardiol 1996;28:472–9. [15] Valsangiacomo Buechel ER, Mertens LL. Imaging the right heart: the use of integrated multimodality imaging. Eur Heart J 2012;33:949–60.
0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.03.181
Drug-eluting balloons for coronary artery disease: an updated meta-analysis of randomized controlled trials☆ Joey S.W. Kwong, Cheuk-Man Yu ⁎ Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, S.H. Ho Cardiovascular Disease and Stroke Centre, Heart Education And Research Training (HEART) Centre and Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong
a r t i c l e
i n f o
Article history: Received 23 January 2013 Accepted 31 March 2013 Available online 2 May 2013 Keywords: Drug-eluting balloon Coronary artery disease Systematic review Meta-analysis
Drug-eluting balloons (DEB) continue to present as a promising percutaneous intervention for the treatment of coronary artery disease (CAD) [1]. Since we performed our meta-analysis of five randomized trials enrolling 349 patients [2], several other studies evaluating DEB in CAD have been completed [3,4]. Therefore, we incorporated the new evidence into an updated meta-analysis to extend the current knowledge on the efficacy and safety of DEB in patients with CAD. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched in December 2012 for eligible randomized controlled trials (RCTs) evaluating DEB in adult patients (≥18 years) with CAD using the search terms “coated balloon” or “eluting balloon.” Studies were selected independently by the two authors, and disagreements were resolved by discussion. The primary clinical outcomes were (i) target lesion revascularization (TLR), (ii) major adverse cardiac events (MACE), (iii) mortality, (iv) myocardial infarction (MI), and (v) stent thrombosis. Secondary outcomes were in-stent and in-segment measurements of late lumen loss, minimal lumen diameter, and binary restenosis. A Mantel–Haenszel randomeffects model was used to calculate odd ratios (ORs) with their 95% confidence intervals (CIs) for dichotomous data; continuous data were analyzed using an inverse variance random-effects model, and mean differences (MDs) with 95% CIs were calculated. Main analyses were conducted using data of the longest follow-up period, and sensitivity analysis exploring the impact of follow-up duration was also pursued. To detect the effect of the inclusion of small studies, a
☆ The authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. ⁎ Corresponding author. Tel.: +852 2632 3127; fax: +852 2645 1699. E-mail address: [email protected] (C.-M. Yu).
sensitivity analysis with the fixed-effect model was also performed. Results were considered to be statistically significant at P b 0.05. Statistical heterogeneity was assessed using the chi-squared test and I2 statistic; I2 values of ≥25%, ≥50%, and ≥75% were categorized as low, moderate, and high heterogeneity, respectively (P b 0.10 for statistical significance). Statistical analysis was performed using the Review Manager 5.2 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). Of the 5042 titles and abstracts retrieved from our literature search, 42 full-text articles were obtained for further assessment, with one additional record identified from personal library. A total of seven studies enrolling 861 participants were eventually included in our meta-analysis, of whom 383 were randomized to DEB, 227 to DES, and 251 to POBA (Table 1) [3–8]. Only one study enrolled participants with de novo lesions (stable or unstable angina); the remaining six studies recruited patients with in-stent restenosis (ISR). Two studies compared DEB vs. DES, four compared DEB vs. POBA, and one study utilized a three-arm approach investigating DEB, DES, and POBA. All the balloon systems used in the included studies were coated with paclitaxel (SeQuent® Please, 4 trials; Paccocath®, 2 trials, Dior®, 1 trial), and all the DES comparison groups used the paclitaxel-eluting Taxus® Liberté® device. Angiographic observations were obtained at 6 to 8 months, with clinical follow-up ranging from 6 months to 5 years. Compared to DES, DEB showed no significant effects in any of the clinical outcomes amongst the overall CAD populations (TLR: OR = 1.38, 95% CI = 0.41–4.72, P = 0.60; MACE: OR = 1.18, 95% CI = 0.43–3.22 P = 0.75; mortality: OR = 0.58, 95% CI = 0.20–1.63, P = 0.30; MI: OR = 0.97, 95% CI = 0.26–3.65, P = 0.97; stent thrombosis: OR = 0.96, 95% CI = 0.06–15.44, P = 0.97) or participants with ISR (TLR: OR = 0.89, 95% CI = 0.17–4.52, P =0.88; MACE: OR = 0.80, 95% CI = 0.26–2.46, P = 0.69; mortality: OR = 0.53, 95% CI = 0.17–1.60, P = 0.26; MI: OR = 0.77, 95% CI = 0.18–3.26, P = 0.72; stent thrombosis: OR = 0.96, 95% CI = 0.06–15.44, P = 0.97). In-stent angiographic observations were reported in only one (PEPCAD II) of the two studies comparing DEB to DES in participants with ISR, and thus meta-analyses were inconclusive. For in-segment measures, no significant differences were observed in the meta-analyses of LLL (MD = − 0.26, 95% CI = − 0.45 to − 0.07, P = 0.48), MLD (MD = 0.01, 95% CI = − 0.14 to 0.15, P = 0.94) or binary restenosis (OR = 0.63, 95% CI = 0.17–2.42, P = 0.50). Participants in the five DEB vs. POBA arms all had ISR. Compared to POBA, treatment of DEB was associated with a significant reduction of TLR