Detecting Coronary Artery Disease Using Rest Seismocardiography and Gyrocardiography.

In this study, we present a non-invasive solution to identify patients with coronary artery disease (CAD) defined as ⩾50% stenosis in at least one coronary artery. The solution is based on the analysis of linear acceleration (seismocardiogram, SCG) and angular velocity (gyrocardiogram, GCG) of the heart recorded in the x, y, and z directional axes from an accelerometer/gyroscope sensor mounted on the sternum. The database was collected from 310 individuals through a multicenter study. The time-frequency features extracted from each SCG and GCG data channel were fed to a one-dimensional Convolutional Neural Network (1D CNN) to train six separate classifiers. The results from different classifiers were later fused to estimate the CAD risk for each participant. The predicted CAD risk was validated against related results from angiography. The SCG z and SCG y classifiers showed better performance relative to the other models (p < 0.05) with the area under the curve (AUC) of 91%. The sensitivity range for CAD detection was 92-94% for the SCG models and 73-87% for the GCG models. Based on our findings, the SCG models achieved better performance in predicting the CAD risk compared to the GCG models; the model based on the combination of all SCG and GCG classifiers did not achieve higher performance relative to the other models. Moreover, these findings showed that the performance of the proposed 3-axial SCG/GCG solution based on recordings obtained during rest was comparable, or better than stress ECG. These data may indicate that 3-axial SCG/GCG could be used as a portable at-home CAD screening tool.

The repeatability of estimated systolic time intervals in healthy subjects using seismocardiogram and electrocardiogram.

OBJECTIVE: We investigated the repeatability of systolic time intervals (STIs) in healthy subjects using a combination of seismocardiogram (SCG) and electrocardiogram (ECG). STIs have been extensively used in the past to quantify heart performance, particularly the left ventricle. In this study, STIs included pre-ejection period (PEP), left ventricular ejection time (LVET), and their ratio. APPROACH: We conducted the repeatability test of STI estimation through two experiments. The first involved three consecutive one-minute recordings separated by one-minute intervals, and the second involved two one-minute recordings separated by 24 h. Twenty healthy subjects participated in our study. We considered the coefficient of variation (CV) to quantify the repeatability. As there was no agreed upon values for optimal CV values, we compared our results with an alternative method using a combination of impedance cardiography (ICG) and ECG. Similar to our method, the alternative method was noninvasive and could be employed for personal heart monitoring. We also studied the repeatability after STIs were corrected for heart rate using two approaches. The first approach used a multiplicative factor per subject based on the heart rates in each recordings of that subject. The second approach employed sex-specific regression models for all subjects (Weissler's equations). MAIN RESULTS: We found that the repeatability of our method (SCG and ECG) was in agreement with the alternative method (ICG and ECG) in both experiments. Moreover, the Weissler's equations approach for heart rate increased the repeatability. SIGNIFICANCE: It can be concluded that estimation of PEP, LVET and their ratio through SCG and ECG signals was repeatable in healthy subjects.

Identifying Patients With Coronary Artery Disease Using Rest and Exercise Seismocardiography.

Coronary artery disease (CAD) is the most common cause of death globally. Patients with suspected CAD are usually assessed by exercise electrocardiography (ECG). Subsequent tests, such as coronary angiography and coronary computed tomography angiography (CCTA) are performed to localize the stenosis and to estimate the degree of blockage. The present study describes a non-invasive methodology to identify patients with CAD based on the analysis of both rest and exercise seismocardiography (SCG). SCG is a non-invasive technology for capturing the acceleration of the chest induced by myocardial motion and vibrations. SCG signals were recorded from 185 individuals at rest and immediately after exercise. Two models were developed using the characterization of the rest and exercise SCG signals to identify individuals with CAD. The models were validated against related results from angiography. For the rest model, accuracy was 74%, and sensitivity and specificity were estimated as 75 and 72%, respectively. For the exercise model accuracy, sensitivity, and specificity were 81, 82, and 84%, respectively. The rest and exercise models presented a bootstrap-corrected area under the curve of 0.77 and 0.91, respectively. The discrimination slope was estimated 0.32 for rest model and 0.47 for the exercise model. The difference between the discrimination slopes of these two models was 0.15 (95% CI: 0.10 to 0.23, p < 0.0001). Both rest and exercise models are able to detect CAD with comparable accuracy, sensitivity, and specificity. Performance of SCG is better compared to stress-ECG and it is identical to stress-echocardiography and CCTA. SCG examination is fast, inexpensive, and may even be carried out by laypersons.

Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms.

BACKGROUND: The progression of compensated hypertrophy to heart failure (HF) is still debated. We investigated patients with isolated valvular aortic stenosis and differing degrees of left ventricular (LV) systolic dysfunction to test the hypothesis that structural remodeling, as well as cell death, contributes to the transition to HF. METHODS AND RESULTS: Structural alterations were studied in LV myectomies from 3 groups of patients (group 1: ejection fraction [EF] >50%, n=12; group 2: EF 30% to 50%, n=12; group 3: EF <30%, n=10) undergoing aortic valve replacement. Control patients were patients with mitral valve stenosis but normal LV (n=6). Myocyte hypertrophy was accompanied by increased nuclear DNA and Sc-35 (splicing factor) content. ACE and TGF-beta1 were upregulated correlating with fibrosis, which increased 2.3-, 2.2-, and 3.2-fold over control in the 3 groups. Myocyte degeneration increased 10, 22, and 32 times over control. A significant correlation exists between EF and myocyte degeneration or fibrosis. Ubiquitin-related autophagic cell death was 0.5 per thousand in control and group 1, 1.05 in group 2, and 6.05 per thousand in group 3. Death by oncosis was 0 per thousand in control, 3 per thousand in group 1, and increased to 5 per thousand (groups 2 and 3). Apoptosis was not detectable in control and group 3, but it was present at 0.02 per thousand in group 1 and 0.01 per thousand in group 2. Cardiomyocyte mitosis was never observed. CONCLUSIONS: These structure-function correlations confirm the hypothesis that transition to HF occurs by fibrosis and myocyte degeneration partially compensated by hypertrophy involving DNA synthesis and transcription. Cell loss, mainly by autophagy and oncosis, contributes significantly to the progression of LV systolic dysfunction.

Structural correlate of atrial fibrillation in human patients.

OBJECTIVE: We tested the hypothesis that structural remodeling of cellular connections, alterations in the expression of connexins (Cx), and an increase in fibrosis represent anatomic substrates of atrial fibrillation (AF). METHODS: In 31 patients with AF undergoing a Maze procedure and 22 patients in sinus rhythm (SR), biopsies were taken intraoperatively from the right atrial (RA) free wall and appendages and investigated with immunoconfocal and electron microscopy. RESULTS: All patients with AF exhibited a concomitant lateralization of gap junctional proteins Cx43 and Cx40, and N-cadherin (the major mechanical junction protein), instead of being confined to the intercalated discs, as observed in SR. These results were confirmed by quantitative immunoconfocal analysis and electron microscopy. Among diverse junctional proteins, in AF, Cx40 was markedly heterogeneous in distribution. As compared with the SR group, Cx43 was significantly decreased in AF by 57% in RA appendages and by 56% in RA free wall. Cx40 was reduced by 54% in appendages, but had a tendency to be increased in the RA free wall. Collagen I was significantly higher in AF than in SR by 48% in RA appendages and by 69% in the RA free wall tissues. CONCLUSIONS: The structural correlate of AF comprises extensive concomitant remodeling of mechanical and electrical junctions, reduction of Cx43, heterogeneous distribution of Cx40 in terms of different amounts of Cx40 in different RA tissues or in spatially adjacent regions of atrial myocardium. These changes, together with augmentation of fibrosis, may underlie localized conduction abnormalities and contribute to initiation and self-perpetuation of re-entry pathways and AF.

Connexin 43 expression and distribution in compensated and decompensated cardiac hypertrophy in patients with aortic stenosis.

OBJECTIVES: Gap junctions (GJ) are important determinants of conduction. In advanced heart failure alterations of the major ventricular GJ protein, connexin 43 (Cx43) are found. However, changes in Cx43 expression during the progression from compensated cardiac hypertrophy to heart failure, especially in humans, have not been studied extensively. The aim of the present study was to investigate changes in Cx43 expression and distribution in compensated and decompensated left ventricular (LV) hypertrophy in pressure-overloaded human hearts with valvular aortic stenosis (AS). METHODS: We measured Cx43 levels by Western blot and quantitative immunoconfocal microscopy of LV septum biopsies from three groups of patients with AS (group I (n=9): ejection fraction (EF)>50%; group II (n=12): EF 30-50%; group III (n=9): EF<30%). LV biopsies from six patients with mitral valve stenosis and two donor hearts served as controls. RESULTS: Only the early phase of LV hypertrophy (AS-I) was characterized by extensive Cx43 lateral staining. As compared to controls, the AS-I group showed a 44.3% increase in Cx43 protein, which was reflected in an augmented number of GJs per 100 microm(2) intercalated disc area (control: 62.5+/-6.4 vs. AS-I: 79.8+/-4, p<0.001) and an increased GJ surface density (control: 0.00547 vs. AS-I: 0.00724 microm(2)/microm(3), p<0.01). Decompensated LV hypertrophy (AS-III) was specified by reduced percentage of the Cx43 signal per myocyte area (control: 1.74% vs. AS-III: 1.31%, p<0.01) or per intercalated disc (control: 18.3% vs. AS-III: 11.3%, p<0.005). Mean GJ area and GJ number per intercalated discs in the AS-III group were decreased significantly by, respectively, 42.5% and 36.4% as compared to control. In addition, decompensated LV myocardium showed a markedly heterogeneous spatial distribution of Cx43. CONCLUSION: The quantity and spatial distribution of Cx43 differs markedly between compensated and decompensated LV hypertrophy in human patients with AS. Upregulation of Cx43 in compensated hypertrophy may represent the immediate adaptive response to increased load, whereas diminished and heterogeneous Cx43 distribution in decompensated hypertrophy may play maladaptive roles culminating in heart failure and ventricular arrhythmias.

Aneurysm formation after patch aortoplasty repair (Vossschulte): reoperation in adults with and without hypothermic circulatory arrest.

BACKGROUND: Aortic aneurysm formation is common after patch aortoplasty repair of coarctation of the aorta. Its incidence varies between 5% and 38%. The majority of patients show progressive aneurysmal dilation within 6 to 18 years and reoperation is necessary to avoid rupture of the aneurysm. METHODS: Ten patients were reoperated on for patch aneurysm formation. Femorofemoral cardiopulmonary bypass (CPB) with a heparinized system was used in all patients. Decision to initiate hypothermic circulatory arrest (HCA) was made intraoperatively. All patients received a Dacron graft replacement of the aneurysmatic thoracic aorta. RESULTS: HCA was initiated in 5 patients owing to extreme adhesions in vicinity to the aneurysm. There was no significant intergroup difference regarding time interval after first operation, age, operation time, and postoperative blood loss. Only minor neurologic events were present in 2 patients with cross-clamping the aorta. CONCLUSIONS: Patch aneurysms after Vossschulte aortoplasty can safely be operated on with femorofemoral CPB. Initiation of HCA is recommended to prevent rupture of the aneurysm during preparation and injury of adjacent nerves and vessels.

Long-term follow-up after the mini-maze procedure.

BACKGROUND: Atrial fibrillation (AF) is associated with significant morbidity and mortality. The standard to treat AF surgically is the Cox maze III procedure but owing to its complexity it is not performed on a regular basis. Meanwhile several maze variants have been developed but their long-term results are still not well known. METHODS: From November 1995 until May 2002 a mini-maze procedure was performed upon 77 patients aged 64 +/- 8.7 years with chronic symptomatic AF. Electrophysiological evaluation, magnetic resonance imaging, echocardiography and electrocardiographic evaluations were performed after 3 and 12 months. After a mean follow-up of 50 +/- 2.6 months a standard questionnaire was sent to all patients. RESULTS: Early and late mortality was 1.2% and 9.3% respectively. Actuarial survival was 91%, 90%, and 87% after 1, 3, and 5 years respectively. Left bundle branch block was an independent risk factor for late death (p = 0.02). Patients who were in sinus rhythm at follow-up had significantly better survival rate as compared with the patients still in AF. Seventy-one percent of patients were in sinus rhythm or paced by an atrial pacemaker. Predictors for restoration of sinus rhythm were absence of preoperative mitral insufficiency (p = 0.03) and larger left atrium (p = 0.04). The presence of preoperative tricuspid insufficiency (p = 0.03) and larger right atrium (p = 0.017) were predictors for postoperative pacemaker implantation. CONCLUSIONS: The mini-maze procedure can be carried out with satisfactory early and long-term results regarding mortality and restoration of sinus rhythm. Prophylactic implantation of biventricular pacemakers in patients with left bundle branch block may decrease late mortality. Every effort should be done to cure AF as it affects long-term survival.

Mitral annuloplasty in patients with ischemic versus dilated cardiomyopathy.

OBJECTIVE: Mitral regurgitation is a frequent finding in patients with end-stage cardiomyopathy predicting poor survival. Conventional treatment consists medical treatment or cardiac transplantation. However, despite severely decreased left ventricular function, mitral annuloplasty may improve survival and reduce the need for allografts. METHODS: From January 1996 to July 2002, 121 patients with severe end-stage dilated (DCM) or ischemic cardiomyopathy (ICM), mitral regurgitation > or =2, and left ventricular ejection fraction < or =30% underwent mitral valve annuloplasty using a flexible posterior ring. DCM was diagnosed in 30 patients (25%), whereas ICM was found in 91 patients (75%). Concomitant tricuspid valve repair was performed in 14 (46.6%) patients in the DCM, and in 11 (12%) in the ICM group (P=0.0001), coronary artery bypass grafting in three (10%) in the DCM, and in 78 patients (86%) in the ICM group (P<0.00001). The mean follow-up time was 567+/-74 days in the DCM and 793+/-63 days in the ICM group (ns). RESULTS: Early mortality was 6.6% (8/121), and was equal for both groups. Improvement in NYHA class (DCM 3.3+0.1-1.8+/-0.16; ICM from 3.2+0.04 to 1.7+/-0.07) were equal between groups after 1 year. Seventeen (15%) late deaths occurred during the follow-up period. There was no difference in the 2-year actuarial survival between groups (DCM/ICM 0.93/0.85). Risk factors for mitral reconstruction failure, defined as regurgitation > or =2 after 1 year, were preoperative NYHA IV in the DCM group (P=0.03), a preoperative posterior infarction (P=0.025), decreased left ventricular function (P=0.043), larger ring size (P=0.026) and preoperative renal failure (P=0.05) in the ICM group. Risk factors for death were larger ring size (P=0.02) and an increased LVEDD (P=0.027) in the DCM group and the postoperative use of IABP (P=0.002), renal failure (P=0.001), and a larger preoperative LVESD (P=0.035) in the ICM group. CONCLUSION: Mitral reconstruction with a posterior annuloplasty using a flexible ring is effective in patients with severely depressed left ventricle function and has an acceptable operative mortality. Mid-term results are superior to medical treatment alone and comparable to cardiac transplantation.

Post-mitral valve repair systolic anterior motion produced by non-obstructive septal bulge.

OBJECTIVE: Systolic anterior motion (SAM) may rarely occur after mitral valve reconstruction due to different anatomic factors. Several techniques have been described to reduce the incidence of post-repair SAM, e.g. leaflet sliding plasty. However, SAM can still occur after these special procedures. We reviewed data of patients developing SAM with significant mitral regurgitation due to non-obstructive septal bulge. METHODS: During a 2-year period mitral valve repair was performed in 358 patients. Five of 358 (1.4%) patients with a mean age of 52+/-10.5 years developed post-repair SAM with severe mitral insufficiency due to non-obstructive septal bulge. Data of these patients were analyzed retrospectively and controlled after a mean follow-up of 18+/-2.7 months. RESULTS: Preoperative echocardiography showed end-diastolic septum diameter of 7, 10, 10, 11 and 15 mm. The ratio between end-diastolic septum diameter and free wall diameter was 1 in four patients and 1.25 in one patient. There was no left ventricular outflow tract obstruction (LVOT). Intraoperative data revealed large myxomatous anterior (four patients) and posterior (three patients) leaflets. Quadrangular resection of posterior leaflet was carried out in four patients and sliding plasty in one patient. Cause for post-repair mitral regurgitation was a non-obstructive septal bulge. During a second pump run septal bulge was resected. Mean aortic cross-clamp time and cardiopulmonary bypass time for this procedure was 15+/-1.4 and 28+/-3.1 min, respectively. Mitral regurgitation disappeared in all patients immediately after this procedure. The grade of mitral regurgitation at follow-up was 0-1 in all patients. One patient had subaortic gradient of 36 mmHg. CONCLUSIONS: If mitral regurgitation occurs after primary successful mitral repair, septum bulge should always be considered as the primary cause for SAM even there is no preoperative gradient in LVOT. Before performing time-consuming corrective operations to relieve SAM, a septum resection should be carried out during a short second pump run.

Gap junction remodeling and altered connexin43 expression in the failing human heart.

Gap junctions (GJ) are important determinants of cardiac conduction and the evidence has recently emerged that altered distribution of these junctions and changes in the expression of their constituent connexins (Cx) may lead to abnormal coupling between cardiomyocytes and likely contribute to arrhythmogenesis. However, it is largely unknown whether changes in the expression and distribution of the major cardiac GJ protein, Cx43, is a general feature of diverse chronic myocardial diseases or is confined to some particular pathophysiological settings. In the present study, we therefore set out to investigate qualitatively and quantitatively the distribution and expression of Cx43 in normal human myocardium and in patients with dilated (DCM), ischemic (ICM), and inflammatory cardiomyopathies (MYO). Left ventricular tissue samples were obtained at the time of cardiac transplantation and investigated with immunoconfocal and electron microscopy. As compared with the control group, Cx43 labeling in myocytes bordering regions of healed myocardial infarction (ICM), small areas of replacement fibrosis (DCM) and myocardial inflammation (MYO) was found to be highly disrupted instead of being confined to the intercalated discs. In all groups, myocardium distant from these regions showed an apparently normal Cx43 distribution at the intercalated discs. Quantitative immunoconfocal analysis of Cx43 in the latter myocytes revealed that the Cx43 area per myocyte area or per myocyte volume is significantly decreased by respectively 30 and 55% in DCM, 23 and 48% in ICM, and by 21 and 40% in MYO as compared with normal human myocardium. In conclusion, focal disorganization of GJ distribution and down-regulation of Cx43 are typical features of myocardial remodeling that may play an important role in the development of an arrhythmogenic substrate in human cardiomyopathies.

Predictors of failure to cure atrial fibrillation with the mini-maze operation.

BACKGROUND: Maze-III is a complex surgical procedure designed to treat chronic atrial fibrillation. A reduction in the number of right and left atrial incisions could decrease the operative time. The aim of this study was to assess the results of a mini-maze operation and to define predictors of its failure. METHODS: Between 1995 and 2000, 72 patients (mean age 64 +/- 9 years) undergoing cardiac surgery had a concomitant mini-maze operation for symptomatic chronic atrial fibrillation. Three and 12 months post-operatively, heart rhythm and left atrial transport functions were assessed by electrophysiology, echocardiography, and magnetic resonance imaging. Multivariate analysis was performed to identify predictors of failure of the mini-maze operation. RESULTS: Operative mortality was 1.4% (1/72). Death during follow-up occurred in 5.6% of patients (4/71), in one due to chronic heart failure. After 1 year, 80% of patients (48/60) were either in sinus rhythm (n = 43; 72%) or had a pacemaker (n = 5; 8%) implanted due to sick sinus syndrome. Intermittent and chronic atrial fibrillation was found in 20% of patients (12/60). Preoperative duration of atrial fibrillation (p = 0.05), preoperative left atrial diameter (p = 0.001), preoperative right atrial diameter (p = 0.02), a reduced left ventricular ejection fraction (p = 0.03), an increased left ventricular end-diastolic diameter (p = 0.04), and the presence of mitral valve stenosis (p = 0.001) were found to be univariate predictors of failure of the mini-maze operation 1 year postoperatively. Multivariate analysis defined preoperative diagnosis of mitral valve stenosis (p = 0.005; OR 117.5), longer duration of preoperative atrial fibrillation (p = 0.01; OR 1.33), and increased preoperative left ventricular end-systolic diameter (p = 0.02; OR 1.2) as incremental independent risk factors for failure of the mini-maze operation to cure chronic atrial fibrillation. CONCLUSION: The mini-maze operation is a safe procedure with similar results to that of Cox's Maze-III operation. The less-invasive mini-maze operation could be applicable even to patients with severely reduced left ventricular function, in whom complex cardiac surgery has to be performed concomitantly as well as in those presenting severe comorbidities.