Very Low Prevalence and Incidence of Atrial Fibrillation among Bolivian Forager-Farmers.

Background: Atrial fibrillation is the most common arrhythmia in post-industrialized populations. Older age, hypertension, obesity, chronic inflammation, and diabetes are significant atrial fibrillation risk factors, suggesting that modern urban environments may promote atrial fibrillation. Objective: Here we assess atrial fibrillation prevalence and incidence among tropical horticulturalists of the Bolivian Amazon with high levels of physical activity, a lean diet, and minimal coronary atherosclerosis, but also high infectious disease burden and associated inflammation. Methods: Between 2005-2019, 1314 Tsimane aged 40-94 years (52% female) and 534 Moseten Amerindians aged 40-89 years (50% female) underwent resting 12-lead electrocardiograms to assess atrial fibrillation prevalence. For atrial fibrillation incidence assessment, 1059 (81% of original sample) Tsimane and 310 Moseten (58%) underwent additional ECGs (mean time to follow up 7.0, 1.8 years, respectively). Findings: Only one (male) of 1314 Tsimane (0.076%) and one (male) of 534 Moseten (0.187%) demonstrated atrial fibrillation at baseline. There was one new (female) Tsimane case in 7395 risk years for the 1059 participants with >1 ECG (incidence rate = 0.14 per 1,000 risk years). No new cases were detected among Moseten, based on 542 risk years. Conclusion: Tsimane and Moseten show the lowest levels of atrial fibrillation ever reported, 1/20 to ~1/6 of rates in high-income countries. These findings provide additional evidence that a subsistence lifestyle with high levels of physical activity, and a diet low in processed carbohydrates and fat is cardioprotective, despite frequent infection-induced inflammation. Findings suggest that atrial fibrillation is a modifiable lifestyle disease rather than an inevitable feature of cardiovascular aging.

The clinical application of the ratio of transmitral early filling velocity to early diastolic strain rate: a systematic review and meta-analysis.

BACKGROUND: The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) has recently emerged as a novel and accurate non-invasive measure of left ventricular (LV) filling pressure. This systematic review and meta-analysis aimed to give an overview of the possible clinical implications of E/e'sr. METHODS: We conducted a systematic review and meta-analysis of all studies involving E/e'sr. Of 598 identified studies, 16 met our inclusion criteria. Studies involving E/e'sr either investigated its prognostic value (n = 9) or its correlation with invasively measured LV filling pressure (n = 7). RESULTS: The pooled meta-analysis showed a significant correlation between E/e'sr and pulmonary capillary wedge pressure (PCWP) measured invasively across the studies assessing this relationship (Cohen's d = 3.90 95% CI [2.38-6.39], p < 0.001) and between E/e'sr and left ventricle end-diastolic pressure (LVEDP) measured invasively across the studies assessing this relationship (Cohen's d = 5.30 95% CI [2.83-9.96], p < 0.001). The pooled analysis of the prognostic studies showed that E/e'sr was a significant predictor of adverse outcomes after multivariable adjustment across the different study populations in a random effects model (overall estimated HR: 1.58 95% CI [1.28-1.96], p < 0.001, per 1 m increase). CONCLUSION: E/e'sr correlates well with invasive measures of LV filling pressure. In addition, E/e'sr provides significant prognostic information across various patient populations. Further studies are needed to test if E/e'sr has an advantage to E/e'.

A Rare Case of Carcinoid Constrictive Pericarditis.

We describe a case of atypical carcinoid heart disease. A 62-year-old woman with well-differentiated neuroendocrine tumor metastatic to the liver and lymph nodes presented with recurrent unilateral pleural effusions and lower extremity edema. Multimodality imaging and workup resulted in the diagnosis of carcinoid-related constrictive pericarditis, a rare form of carcinoid heart disease. (Level of Difficulty: Intermediate.).

A Complex Tricuspid Clip: Bridging the Decision.

We present this case of a 22-year-old woman with congenital heart disease as the youngest reported patient, to the best of our knowledge, to successfully undergo treatment of medically refractory torrential tricuspid regurgitation with the MitraClip system as an adjunct to guideline directed therapy. (Level of Difficulty: Advanced.).

Ratio of transmitral early filling velocity to early diastolic strain rate predicts long-term risk of cardiovascular morbidity and mortality in the general population.

Aims: It has previously been demonstrated that the ratio of early mitral inflow velocity to global diastolic strain rate (E/e'sr) is a significant predictor of cardiac events in specific patient populations. The utility of this measurement to predict cardiovascular events in a general population has not been evaluated. Methods and results: A total of 1238 participants in a general population study underwent a health examination including echocardiography where global longitudinal strain (GLS) and E/e'sr were determined. The primary endpoint was the composite of incident heart failure (HF), acute myocardial infarction (AMI) or cardiovascular death (CVD). During follow-up (median 11 years), 140 (11.3%) participants reached the composite endpoint. E/e'sr was associated with adverse outcome [HR 1.17 95% CI (1.13-1.21); P < 0.001, per 10 cm increase]. After multivariable adjustment for echocardiographic and clinical parameters, E/e'sr remained an independent predictor of the composite endpoint [HR 1.08, 95% CI (1.02-1.13); P = 0.003] as opposed to E/e' [HR 1.03, 95% CI (0.99-1.06); P = 0.11 per 1 unit increase]. Global longitudinal strain modified the relationship between E/e'sr and outcome (P for interaction = 0.015). E/e'sr was a stronger predictor in participants with good systolic function as determined by GLS (GLS > 18%) after multivariable adjustment, when compared to participants with reduced systolic function (GLS < 18%) [HR 1.28 95% CI (1.06-1.54); P = 0.011, and HR 1.08 95% CI (1.02-1.14); P = 0.012, respectively). E/e'sr provided incremental information [Harrell's C-index: 0.839 (0.81-0.87) vs. 0.844 (0.82-0.87); P = 0.045] beyond the SCORE risk chart. Conclusion: In the general population, E/e'sr provides independent and incremental prognostic information regarding cardiovascular morbidity and mortality. Additionally, E/e'sr is a stronger predictor of cardiac events than E/e'.

Guidelines for the Use of Echocardiography in the Evaluation of a Cardiac Source of Embolism.

Embolism from the heart or the thoracic aorta often leads to clinically significant morbidity and mortality due to transient ischemic attack, stroke or occlusion of peripheral arteries. Transthoracic and transesophageal echocardiography are the key diagnostic modalities for evaluation, diagnosis, and management of stroke, systemic and pulmonary embolism. This document provides comprehensive American Society of Echocardiography guidelines on the use of echocardiography for evaluation of cardiac sources of embolism. It describes general mechanisms of stroke and systemic embolism; the specific role of cardiac and aortic sources in stroke, and systemic and pulmonary embolism; the role of echocardiography in evaluation, diagnosis, and management of cardiac and aortic sources of emboli including the incremental value of contrast and 3D echocardiography; and a brief description of alternative imaging techniques and their role in the evaluation of cardiac sources of emboli. Specific guidelines are provided for each category of embolic sources including the left atrium and left atrial appendage, left ventricle, heart valves, cardiac tumors, and thoracic aorta. In addition, there are recommendation regarding pulmonary embolism, and embolism related to cardiovascular surgery and percutaneous procedures. The guidelines also include a dedicated section on cardiac sources of embolism in pediatric populations.

Lambl's Excrescences: Association with Cerebrovascular Disease and Pathogenesis.

BACKGROUND: Lambl's excrescences (LEx) are detected by transesophageal echocardiography (TEE) and are characterized as thin, elongated, and hypermobile structures located at the leaflets' coaptation point of the heart valves. The association of LEx with cerebrovascular disease (CVD) is still undefined and yet patients with LEx and suspected CVD receive unproven effective antiplatelet or anticoagulant therapy or even undergo valve surgery. Also, the association of LEx with aging and atherogenic, inflammatory, or thrombogenic parameters has not been reported. METHODS: Seventy-seven patients with systemic lupus erythematosus (SLE) (71 women, age 37 ± 12 years) and 26 age- and sex-matched healthy controls (22 women, age 34 ± 11 years) prospectively underwent routine history and physical exam, transcranial Doppler, brain MRI, TEE, carotid duplex, and clinical and laboratory evaluations of atherogenesis, inflammation, platelet activity, coagulation, and fibrinolysis. Subjects without stroke/TIA on enrollment (with and without LEx) had a median follow-up of 57 months. RESULTS: On enrollment, 33 (43%) of 77 patients had CVD manifested as acute stroke/TIA (23 patients), cerebromicroembolism by transcranial Doppler (17 patients), or cerebral infarcts by MRI (14 patients). Mitral or aortic valve LEx were equally frequent in healthy controls (46%) as in patients with and without any CVD (39 and 43%), stroke/TIA (35 and 43%), cerebromicroembolism (41 and 42%), or cerebral infarcts (36 and 43%) (all p ≥ 0.72). Also, other mechanisms for CVD other than LEx such as Libman-Sacks vegetations, patent foramen ovale or interatrial septal aneurysm, aortic or carotid atherosclerosis, or thrombogenesis were found in ≥94% of patients with CVD. In addition, 36 subjects with and 44 without LEx had similar low incidence of stroke/TIA (1 (1.3%) and 2 (2.5%), respectively, p = 1.0) during follow-up. Finally, LEx were not associated with aging, atherogenic risk factors, atherosclerosis, inflammation, or thrombogenesis. CONCLUSIONS: In this study, LEx are similarly prevalent in healthy controls and SLE patients, are not associated with CVD, and are not associated with pathogenic risk factors. Therefore, the study findings suggest that LEx may not be cardioembolic substrates, may not represent pathologic valve structures, and may not require therapy.

Libman-Sacks Endocarditis: Detection, Characterization, and Clinical Correlates by Three-Dimensional Transesophageal Echocardiography.

BACKGROUND: Libman-Sacks endocarditis, characterized by Libman-Sacks vegetations, is common in patients with systemic lupus erythematosus and is commonly complicated with embolic cerebrovascular disease. Thus, accurate detection of Libman-Sacks vegetations may lead to early therapy and prevention of their associated complications. Although two-dimensional (2D) transesophageal echocardiography (TEE) has high diagnostic value for detection of Libman-Sacks vegetations, three-dimensional (3D) TEE may allow improved detection, characterization, and clinical correlations of Libman-Sacks vegetations. METHODS: Twenty-nine patients with systemic lupus erythematosus (27 women; mean age, 34 ± 12 years) prospectively underwent 40 paired 3D and 2D transesophageal echocardiographic studies and assessment of cerebrovascular disease manifested as acute clinical neurologic syndromes, neurocognitive dysfunction, or focal brain injury on magnetic resonance imaging. Initial and repeat studies in patients were intermixed in a blinded manner with paired studies from healthy controls, deidentified, coded, and independently interpreted by experienced observers unaware of patients' clinical and imaging data. RESULTS: The results of 3D TEE compared with 2D TEE were more often positive for mitral or aortic valve vegetations, and 3D TEE detected more vegetations per study and determined larger sizes of vegetations (P ≤ .03 for all). Also, 3D TEE detected more vegetations on the anterior mitral leaflet, anterolateral and posteromedial scallops, and ventricular side or both atrial and ventricular sides of the leaflets (P < .05 for all). In addition, 3D TEE detected more vegetations on the aortic valve left and noncoronary cusps, coronary cusps' tips and margins, and aortic side or both aortic and ventricular sides of the cusps (P ≤ .01 for all). Furthermore, 3D TEE more often detected associated mitral or aortic valve commissural fusion (P = .002). Finally, 3D TEE detected more vegetations in patients with cerebrovascular disease (P = .01). CONCLUSIONS: Three-dimensional TEE provides clinically relevant additive information that complements 2D TEE for the detection, characterization, and association with cerebrovascular disease of Libman-Sacks endocarditis.

Comparison of two-dimensional versus real-time three-dimensional transesophageal echocardiography for evaluation of patent foramen ovale morphology.

The aim of this study was to elucidate patent foramen ovale (PFO) morphology and the change of PFO size using real-time 3-dimensional (3D) transesophageal echocardiography (TEE). PFO is a 3D structure, and its shape changes during the cardiac cycle. Therefore, it may be difficult to estimate accurate PFO morphology using 2-dimensional (2D) TEE. The study included 50 patients with PFO who underwent 2D and 3D TEE. PFO heights (PHs) at entrance, mid, and exit were measured by 2D and 3D TEE. Systolic and diastolic areas were also measured by 3D TEE. PH by 3D TEE was larger than that by 2D TEE (entrance 0.32 ± 0.18 vs 0.21 ± 0.15 cm, p <0.001; mid 0.25 ± 0.14 vs 0.15 ± 0.11 cm, p <0.001; exit 0.19 ± 0.11 vs 0.11 ± 0.08 cm, p <0.001). Systolic area was greater than diastolic area at each location (entrance 0.19 ± 0.17 vs 0.11 ± 0.11 cm(2), p = 0.001; mid 0.13 ± 0.11 vs 0.08 ± 0.06 cm(2), p = 0.001; exit 0.09 ± 0.09 vs 0.06 ± 0.05 cm(2), p = 0.01). Additionally, entrance area was greater than exit area in systole and diastole (systole 0.19 ± 0.17 vs 0.09 ± 0.09 cm(2), p <0.001; diastole 0.11 ± 0.11 vs 0.06 ± 0.05 cm(2), p = 0.001). There were good correlations between PH by 3D TEE and PFO area (entrance r = 0.68, mid r = 0.71, exit r = 0.78) but weak correlations between PH by 2D TEE and PFO area (entrance r = 0.62, mid r = 0.50, exit r = 0.51). In conclusion, real-time 3D TEE could provide detailed and unique information on PFO morphology.

Comparison of real-time three-dimensional transesophageal echocardiography to two-dimensional transesophageal echocardiography for quantification of mitral valve prolapse in patients with severe mitral regurgitation.

Real-time 3-dimensional (3D) transesophageal echocardiography (TEE) provides more accurate geometric information on the mitral valve (MV) than 2-dimensional (2D) TEE. The aim of this study was to quantify MV prolapse using real-time 3D TEE in patients with severe mitral regurgitation. In 102 patients with severe mitral regurgitation due to MV prolapse and/or flail, 2D TEE quantified MV prolapse, including prolapse gap and width in the commissural view. Three-dimensional TEE also determined prolapse gap and width with the use of the 3D en face view. On the basis of the locations of MV prolapse, all patients were classified into group 1 (pure middle leaflet prolapse, n = 50) or group 2 (involvement of medial and/or lateral prolapse, n = 52). Prolapse gap and prolapse width determined by 3D TEE were significantly greater than those by 2D TEE (all p values <0.001). The differences in prolapse gap and prolapse width between 2D TEE and 3D TEE were significantly greater in group 2 than group 1 (Δ gap 1.3 ± 1.4 vs 2.4 ± 1.8 mm, Δ width 2.5 ± 3.0 vs 4.4 ± 5.1 mm, all p values <0.01). The differences in prolapse gap and width between 2D TEE and 3D TEE were best correlated with 3D TEE-derived prolapse width (r = 0.41 and r = 0.74, respectively). Two-dimensional TEE underestimated the width of MV prolapse and leaflet gap compared to 3D TEE. Two-dimensional TEE could not detect the largest prolapse gap and width, because of the complicated anatomy of the MV. In conclusion, 3D TEE provided more precise quantification of MV prolapse than 2D TEE.

Non-circular shape of right ventricular outflow tract: a real-time 3-dimensional transesophageal echocardiography study.

BACKGROUND: The shape of right ventricular outflow tract (RVOT) has been assumed to be circular. The aim of this study was to assess RVOT morphology using 3-dimensional transesophageal echocardiography (3D TEE). METHODS AND RESULTS: This prospective study included 114 patients who underwent 3D TEE. Two-dimensional (2D) TEE measured maximum and minimum RVOT diameters (RVOTD max and min) during a cardiac cycle. 3D TEE determined RVOT area (RVOTA) max and min, RVOT fractional area change, and RVOT shape index (RVOTSI; vertical/horizontal RVOTD). Cardiac output (CO) was calculated using 2D TEE, 3D TEE, and a Swan-Ganz catheter in 23 patients. All patients were classified into group 1 (RVOTSI ≤1) or group 2 (RVOTSI >1) based on the RVOT shapes. The mean RVOTSIs were 0.84±0.21(max) and 0.82±0.20 (min). Only 17 patients (14.9%) had circular RVOT (RVOTSI: 0.95-1.05); 82 patients (71.9%) were categorized into group 1 and 32 patients (28.1%) into group 2. 2D TEE, compared with 3D TEE, underestimated RVOTA max and min (both P<0.001). CO with 3D TEE had better agreement with CO with a catheter than CO with 2D TEE (r=0.83 and 0.53, respectively). CONCLUSIONS: 3D TEE revealed that RVOT geometry was not generally circular but oval with 2 different types. Because of the detailed morphological information of RVOT, 3D TEE could provide more accurate assessment of CO than 2D TEE.

Echocardiographic evaluation of iatrogenic atrial septal defect after catheter-based mitral valve clip insertion.

The geometries and sizes of persistent iatrogenic atrial septal defects (IASDs) after transseptal puncture during catheter-based mitral valve clip insertion (MVCI) have not been detailed. In this study, 11 IASDs were investigated in 10 patients who underwent MVCI using a guide catheter (24Fr proximally and 22Fr at the atrial septum). The diameters of the long and short axes and the area at maximum and minimum during a cardiac cycle were measured after MVCI using real-time 3-dimensional (RT3D) transesophageal echocardiography (TEE). A circular shape was assumed on 2-dimensional TEE, resulting in an area calculation of π × (dimension/2)(2). The anatomic geometries of IASDs were visualized in a 3-dimensional en face view of the atrial septum. Furthermore, 1 month after MVCI, IASDs were evaluated using echocardiography. The IASDs had a variety of irregular geometries. The mean long-axis diameter was 1.0 ± 0.24 cm, the mean short-axis diameter was 0.51 ± 0.22 cm, and the mean area was 0.40 ± 0.24 cm(2) on RT3D TEE. The diameters and area changed significantly between the maximal and minimal values during the cardiac cycle. Importantly, 2-dimensional TEE underestimated the maximal diameters of IASDs (0.54 ± 0.17 vs 1.0 ± 0.24 cm by RT3D TEE, p <0.01) and the maximal areas of IASDs (0.25 ± 0.15 vs 0.40 ± 0.23 cm(2) by RT3D TEE, p <0.05). One month after MVCI, the smallest and the second smallest IASDs had closed, and the other 9 remained open. In conclusion, RT3D TEE is useful to assess the irregular geometries of IASDs created during MVCI.

Comparison of left ventricular outflow geometry and aortic valve area in patients with aortic stenosis by 2-dimensional versus 3-dimensional echocardiography.

The present study sought to elucidate the geometry of the left ventricular outflow tract (LVOT) in patients with aortic stenosis and its effect on the accuracy of the continuity equation-based aortic valve area (AVA) estimation. Real-time 3-dimensional transesophageal echocardiography (RT3D-TEE) provides high-resolution images of LVOT in patients with aortic stenosis. Thus, AVA is derived reliably with the continuity equation. Forty patients with aortic stenosis who underwent 2-dimensional transthoracic echocardiography (2D-TTE), 2-dimensional transesophageal echocardiography (2D-TEE), and RT3D-TEE were studied. In 2D-TTE and 2D-TEE, the LVOT areas were calculated as π × (LVOT dimension/2)(2). In RT3D-TEE, the LVOT areas and ellipticity ([diameter of the anteroposterior axis]/[diameter of the medial-lateral axis]) were evaluated by planimetry. The AVA is then determined using planimetry and the continuity equation method. LVOT shape was found to be elliptical (ellipticity of 0.80 ± 0.08). Accordingly, the LVOT areas measured by 2D-TTE (median 3.7 cm(2), interquartile range 3.1 to 4.1) and 2D-TEE (median 3.7 cm(2), interquartile range 3.1 to 4.0) were smaller than those by 3D-TEE (median 4.6 cm(2), interquartile range 3.9 to 5.3; p <0.05 vs both 2D-TTE and 2D-TEE). RT3D-TEE yielded a larger continuity equation-based AVA (median 1.0 cm(2), interquartile range 0.79 to 1.3, p <0.05 vs both 2D-TTE and 2D-TEE) than 2D-TTE (median 0.77 cm(2), interquartile range 0.64 to 0.94) and 2D-TEE (median 0.76 cm(2), interquartile range 0.62 to 0.95). Additionally, the continuity equation-based AVA by RT3D-TEE was consistent with the planimetry method. In conclusion, RT3D-TEE might allow more accurate evaluation of the elliptical LVOT geometry and continuity equation-based AVA in patients with aortic stenosis than 2D-TTE and 2D-TEE.

Left atrial size and function are related to pulmonary hypertension in coronary artery disease.

BACKGROUND: Left atrial (LA) size reflects diastolic burden and is a prognostic parameter of common cardiovascular death. However, the association between LA size and function and pulmonary hypertension (PH) in coronary artery disease (CAD) has not been well investigated. We hypothesized that LA size and function are associated with PH in CAD. METHODS: One hundred seven patients with CAD were studied. LA size was determined in three different methods; namely, LA volume index (LAV), LA area index, and LA dimension. LAV total emptying fraction was also determined. Pulsed Doppler E, A, E/A, DT, tissue Doppler E', A', and E/E' were measured. Pulmonary artery systolic pressure (PASP) was estimated. RESULTS: All LA size parameters are significantly associated with PH. LAV emptying fraction, age, E, E/A, E/E', and A' were also associated with PH significantly. CAD patients with PH showed larger LA size, higher E, E/A, and E/E' and lower LAV emptying fraction, A and A' than CAD patients without PH. Multivariate regression analysis revealed that maximum LAV, E, E/A ratio, and age were independent predictors of PH. Maximum LAV > 35.6 mL/m(2) predicted PASP > 40 mmHg with a sensitivity of 83.9% and specificity of 62.2%. CONCLUSION: LAV is associated with PH in CAD patients.

Atropine as an adjunct to supine bicycle stress echocardiography: an alternative strategy to achieve target heart rate or rate pressure product.

AIMS: To investigate the use of atropine to achieve target heart rate (THR) and rate pressure product (RPP) during supine bicycle exercise stress echocardiography (SBESE) to increase the number of diagnostic stress tests. METHODS AND RESULTS: Forty-four patients that were unable to achieve THR or RPP during SBESE performed to evaluate ischaemia were given 0.4-1.2 mg of atropine to augment THR and RPP. After atropine (0.7 ± 0.3 mg) the maximum heart rate (HR) achieved was 133 (± 16) bpm, mean THR was 82% (± 8%), and average RPP was 22 716 (± 4915) b/min × mmHg. Of the patients with a non-diagnostic SBESE, with the use of atropine 80% of those patients achieved a diagnostic test. There were no major adverse affects from the administration of atropine. CONCLUSION: The use of atropine to augment the HR or RPP during SBESE (i) is safe; (ii) enables the assessment of ischaemia at peak effort; and (iii) allows assessment of exercise haemodynamics in patients with sub-maximal exercise capacity and chronotropic incompetence.

Left atrial myxomas: correlation of two-dimensional and live three-dimensional transesophageal echocardiography with the clinical and pathologic findings.

BACKGROUND: Although transthoracic echocardiography and two-dimensional transesophageal echocardiography (TEE) identify cardiac myxomas with high sensitivity, anatomic and morphologic information is often incomplete. Real-time three-dimensional (3D) TEE is increasingly being used in general clinical practice. However, the use of real-time 3D TEE for the assessment of atrial myxomas has not been described. METHODS: This case series of 10 patients with left atrial myxomas undergoing two-dimensional and real-time 3D TEE. RESULTS: Correlative pathologic findings demonstrate that 3D imaging accurately identifies these tumors and provides detailed morphologic description of the tumors, which may have clinical importance. CONCLUSIONS: Because the 3D TEE is real time and can be performed preoperatively in the operating room, the surgeon may gain a better understanding of the nature and location of the tumor.

Utility of three-dimensional transesophageal echocardiography in the diagnosis of valvular perforations.

Three-dimensional (3D) transesophageal echocardiographic (TEE) imaging is a relatively new imaging modality that is increasingly being used to characterize a variety of cardiac pathologic features. In the present study, we reviewed the 2-dimensional (2D) and 3D TEE images from our echocardiographic database to identify patients with valve perforations. A review of the 2D TEE images resulted in the identification of 11 valvular perforations (6 aortic valves, 4 mitral valves, and 1 tricuspid valve). A review of the 3D TEE images allowed for the identification of 15 valve perforations (7 aortic valves, 7 mitral valves, and 1 tricuspid valve), including 4 perforations that could not be diagnosed using 2D imaging alone. In conclusion, 3D TEE imaging provided added benefit to traditional 2D TEE imaging because of its ability to provide en face visualization of the cardiac valves, allowing improved identification and precise anatomic localization of the perforation.