Beat-to-beat alterations of acoustic intensity and frequency at the maximum power of heart sounds are associated with NT-proBNP levels.

Background: Auscultatory features of heart sounds (HS) in patients with heart failure (HF) have been studied intensively. Recent developments in digital and electrical devices for auscultation provided easy listening chances to recognize peculiar sounds related to diastolic HS such as S3 or S4. This study aimed to quantitatively assess HS by acoustic measures of intensity (dB) and audio frequency (Hz). Methods: Forty consecutive patients aged between 46 and 87 years (mean age, 74 years) with chronic cardiovascular disease (CVD) were enrolled in the present study after providing written informed consent during their visits to the Kitasato University Outpatient Clinic. HS were recorded at the fourth intercostal space along the left sternal border using a highly sensitive digital device. Two consecutive heartbeats were quantified on sound intensity (dB) and audio frequency (Hz) at the peak power of each spectrogram of S1-S4 using audio editing and recording application software. The participants were classified into three groups, namely, the absence of HF (n = 27), HF (n = 8), and high-risk HF (n = 5), based on the levels of NT-proBNP < 300, ≥300, and ≥900 pg/ml, respectively, and also the levels of ejection fraction (EF), such as preserved EF (n = 22), mildly reduced EF (n = 12), and reduced EF (n = 6). Results: The intensities of four components of HS (S1-S4) decreased linearly (p < 0.02-0.001) with levels of body mass index (BMI) (range, 16.2-33.0 kg/m2). Differences in S1 intensity (ΔS1) and its frequency (ΔfS1) between two consecutive beats were non-audible level and were larger in patients with HF than those in patients without HF (ΔS1, r = 0.356, p = 0.024; ΔfS1, r = 0.356, p = 0.024). The cutoff values of ΔS1 and ΔfS1 for discriminating the presence of high-risk HF were 4.0 dB and 5.0 Hz, respectively. Conclusions: Despite significant attenuations of all four components of HS by BMI, beat-to-beat alterations of both intensity and frequency of S1 were associated with the severity of HF. Acoustic quantification of HS enabled analyses of sounds below the audible level, suggesting that sound analysis might provide an early sign of HF.

Association between fingertip-measured advanced glycation end products and cardiovascular events in outpatients with cardiovascular disease.

BACKGROUND: The accumulation of advanced glycation end products (AGEs) is associated with cardiovascular events in patients with cardiovascular disease (CVD). However, the relationship between the AGEs measured by an AGEs sensor noninvasively at the fingertip and prognosis in patients with CVD remains unclear. Therefore, this study aimed to determine the relationship between AGEs score and prognosis among patients with CVD. METHODS: A total of 191 outpatients with CVD were included. AGEs score were measured using an AGEs sensor and the patients were classified into groups by the median value of AGEs score. The incidence of major adverse cardiovascular and cerebrovascular events (MACCE) at 30 months was compared between high- and low-AGEs score groups. In addition, receiver operating characteristic (ROC) curve analysis was used to calculate cutoff value for the AGEs score, which discriminates the occurrence of MACCE. Cox regression analysis was performed to identify the factors associated with the presence of MACCE. MACCE included cardiac death, myocardial infarction, percutaneous coronary intervention, heart failure, and stroke. RESULTS: AGEs score was normally distributed, with a median value of 0.51. No significant intergroup differences were found in laboratory findings, physical functions, or medications. The high-AGEs score group had a significantly higher incidence of MACCE than the low-AGEs score group (27.1 vs. 10.5%, P = 0.007). A high-AGEs score was a risk factor for MACCE (hazard ratio, 2.638; 95% confidence interval, 1.271-5.471; P = 0.009). After the adjustment for confounders other than 6-min walking distance, the AGEs score remained a factor associated with the occurrence of MACCE. The best cutoff AGEs score for the detection of MACCE was 0.51 (area under the curve, 0.642; P = 0.008; sensitivity, 72.2%; specificity, 54.8%). CONCLUSIONS: AGEs score measured at the fingertip in patients with CVD is associated with MACCE. AGEs score, which can be measured noninvasively and easily, may be useful as an assessment for the secondary prevention of CVD in patients with CVD.

Optical coherence tomography factors for adverse events in patients with severe coronary calcification.

BACKGROUND: Severe coronary calcification is a factor for worse outcomes after percutaneous coronary intervention. AIMS: To identify factors of pre- and post-stent optical coherence tomography (OCT) for device-oriented clinical endpoints (DoCE) in patients with severely calcified lesions requiring drug-eluting stent (DES) implantation. METHODS: A total of 237 consecutive patients with stable coronary disease who underwent OCT imaging of severe coronary lesions were included. Lesions with a maximum calcium angle >180°, maximum calcium thickness > 0.5 mm, and calcium length > 5 mm were defined as having severe calcification. RESULTS: The prevalence of eruptive calcified nodules (41% vs. 18%, p = 0.002) and medial dissection with calcified flaps (59% vs. 26%, p < 0.001) was significantly higher in patients with DoCE (n = 34) than those without DoCE (n = 203). Multivariate analyses demonstrated that the presence of a medial dissection with calcified flap within the DES-implanted segment was independently associated with a higher incidence of DoCE (odds ratio, 3.367; 95% confidence interval, 1.503-7.543; p = 0.003). The combined presence of eruptive calcified nodules and medial dissection with calcified flaps was associated with a higher incidence of DoCE (p < 0.001) during a median of 756 days after DES implantation. CONCLUSIONS: OCT-defined severely calcified lesions with eruptive calcified nodules and medial dissection with calcified flaps were associated with a higher incidence of DoCE after DES implantation.

Clinical outcomes and plaque characteristics in patients with coronary artery disease and concomitant sleep-disordered breathing treated by continuous positive airway pressure.

BACKGROUND: Sleep-disordered breathing (SDB) is a risk factor for recurrent adverse events in patients with coronary artery disease (CAD). However, the prognosis of continuous positive alveolar pressure (CPAP) treatment for SDB with CAD remains unknown. METHODS: A total of 281 consecutive patients with stable CAD requiring percutaneous coronary intervention (PCI) were included and classified into three groups according to the concomitance of SDB and CPAP treatment (untreated SDB group, n = 61; CPAP-SDB group, n = 24; and non-SDB group, n = 138). The incidence of major adverse cardiac and cerebrovascular events (MACCEs) within a year after PCI was compared between the three groups. The characteristics of the culprit plaques, including macrophage accumulation, were further assessed using optical coherence tomography. RESULTS: The incidence of MACCEs was significantly different among the three groups (p = 0.037), with the highest incidence in the untreated-SDB group (22.9%) and 8.3% and 10.1% in the CPAP-SDB and non-SDB groups, respectively. The incidence of MACCEs at 1 year was significantly lower in patients with appropriate CPAP use than that in inadequately treated patients with SDB (0.0 vs. 22.5%, p = 0.048). Macrophage accumulation differed significantly among the three groups, with the highest accumulation in the untreated SDB group. CONCLUSIONS: CPAP treatment for SDB may be associated with a lower incidence of MACCEs following PCI and a lower prevalence of macrophages in the culprit plaques.

Advanced Glycation End Products Are Associated with Diabetes Status and Physical Functions in Patients with Cardiovascular Disease.

Advanced glycated end products (AGEs) accumulate systemically and cause diabetes complications. However, whether noninvasive measurable AGEs are associated with diabetes status and physical functions remains unclear. One hundred and ten patients with cardiovascular disease (CVD) who underwent outpatient cardiac rehabilitation were included. AGEs scores, using AGEs sensors, were evaluated concomitantly with a physical evaluation, including testing the isometric knee extension strength (IKES) and 6 min walking distance (6MWD). Thirty-three (30%) patients had a history of diabetes mellitus (DM). The AGEs score was not different in the presence of DM history (0.52 ± 0.09 vs. 0.51 ± 0.09, p = 0.768) and was not correlated with blood glucose (r = 0.001, p = 0.995). The AGEs score was positively correlated with hemoglobin A1c (HbA1c, r = 0.288, p = 0.004) and negatively correlated with physical functions (IKES, r = −0.243, p = 0.011; 6MWD, r = −0.298, p = 0.002). The multivariate analysis demonstrated that 6MWD was independently associated with a high AGEs score (>0.52). The AGEs score was associated with HbA1c, IKES, and 6MWD in patients with CVD. The AGEs score might be a useful indicator for evaluating not only glycemic control but also physical functions.

A case with recovery from high degree atrioventricular-block with steroid therapy in cardiac sarcoidosis with AH block: a possible new sign of responder?

BACKGROUND: Although some reports have documented cases who exhibited recovery from atrioventricular block (AVB) by steroid therapy in cases with cardiac sarcoidosis (CS), they could not determine predictors for such good response to steroid therapy. In this case, a 54-year-old female was referred to our hospital due to intermittent 2:1 AVB. Echocardiography revealed normal ventricular function. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) exhibited enhanced uptake in basal anterior-septal area of the left ventricle. The electrophysiologic study exhibited marked AH prolongation (324 ms) but no HV prolongation. Sarcoidosis was diagnosed basing on non-caseating granulomas detected in skin biopsy. Because the 2:1 AVB was temporal, oral prednisolone (PSL) was started without planning implantation of permanent pacemaker. In 10 days from start of PSL, PR interval was gradually normalized from 0.34 to 0.14 sec and temporal 2:1 AVB disappeared. 18F-FDG PET also exhibited disappearance of enhanced uptake. During the following 2 years, the patient continued to exhibit normal PR interval. This case exhibited AH prolongation in EPS, although the degree of AVB was serious. Additionally, 18F-FDG PET exhibited enhanced uptake in the area around AV-node. AH block and FDG enhancement around AV-node area might be novel predictors for good response to PSL in cases with CS. .

Achilles tendon thickening is associated with higher incidence of adverse cardiovascular event in patients with coronary artery disease.

Achilles tendon thickening (ATT) is a marker of high risk for coronary artery disease (CAD). However, the association between the presence of ATT and the incidence of cardiovascular events in patients with CAD is unclear. A total of 406 consecutive patients who underwent percutaneous coronary intervention (PCI) and ATT assessment were analyzed. ATT was defined as the Achilles tendon thickness of 9 mm or more on radiography. The incidence of major adverse cardiovascular events (MACE) at 1-year was compared between patients with ATT and those without ATT. MACE included cardiac death, non-fatal myocardial infarction, stroke, target vessel revascularization (TVR), and non-TVR. ATT was found in 67 patients (16.5%). The incidence of cardiac death (3.2 vs. 0.0%, p = 0.001), TVR (12.7 vs. 4.0%, p = 0.005) and MACE (20.6 vs. 9.6%, p = 0.011) was significantly higher in the ATT group than the no ATT group. Patients with ATT had significantly higher incidence of cardiac death (5.6 vs. 0%, p < 0.001) than those without ATT even if they did not meet the diagnostic criteria of familial hypercholesterolemia. A multivariate model demonstrated that ATT was independently associated with the MACE at 1-year (Hazard ratio, 2.09; 95% Confidence Interval, 1.09-4.00, p = 0.026). The presence of ATT was independently associated with 1-year recurrence of cardiovascular events in patients with CAD undergoing PCI. Assessment of ATT might be useful for risk stratification of secondary cardiovascular events.

Endothelial glycocalyx and severity and vulnerability of coronary plaque in patients with coronary artery disease.

BACKGROUND AND AIMS: Endothelial glycocalyx covers the endothelium and maintains vascular integrity. However, its association with the severity and vulnerability of coronary artery disease (CAD) remains to be elucidated. METHODS: A total of 259 consecutive patients with stable CAD requiring percutaneous coronary intervention (PCI) were prospectively enrolled. Patients were classified into 2 groups according to the median value of serum syndecan-1, which is a core component of the endothelial glycocalyx (lower syndecan-1 group [syndecan-1 <99.0 ng/mL], n = 130; higher syndecan-1 group [syndecan-1 ≥99.0 ng/mL], n = 129). Severity of CAD and focal plaque vulnerability in culprit lesion were evaluated using angiography and optical coherence tomography. RESULTS: There was no significant difference in clinical characteristics between the lower syndecan-1 group and the higher syndecan-1 group other than the prevalence of family history of CAD (19 vs. 32%, p = 0.022), prior PCI history (45 vs. 60%, p = 0.015) and estimated glomerular filtration rate (57.8 ± 17.2 vs. 50.9 ± 25.6 ml/min/1.73 m2, p = 0.011). Although disease severity on angiogram was comparable between the 2 groups, the prevalence of lipid-rich plaque (40 vs. 19%, p = 0.004) and thin-cap fibroatheroma (20 vs. 6%, p = 0.006) was significantly higher in the lower syndecan-1 group than the higher syndecan-1 group. Lower syndecan-1 level was independently associated with higher prevalence of lipid-rich plaque (odds ratio 3.626, 95% confidence interval 1.535-8.566, p = 0.003). CONCLUSIONS: Lower syndecan-1 level was associated with higher prevalence of vulnerable plaque in patients with CAD. This finding suggests the association between impaired endothelial glycocalyx and the development of vulnerable plaque.

Effect of cardiac rehabilitation on cognitive function in elderly patients with cardiovascular diseases.

BACKGROUND: Cognitive function is an important factor for secondary prevention in elderly patients with cardiovascular diseases. The objective of this study was to evaluate the impact of cardiac rehabilitation (CR) on the improvement of cognitive function. METHODS: A total of 66 consecutive elderly patients (≥70 years old) with cardiovascular diseases were prospectively enrolled. The change in cognitive function during 6 months was compared between the patients with monthly CR (at least once per month; n = 27) and those without monthly CR (n = 39). Cognitive function was evaluated using the Mini-mental State Examination (MMSE) and Frontal Assessment Battery (FAB). RESULTS: There was no significant difference in baseline characteristics between the 2 groups. The change in the MMSE score was significantly greater in patients with monthly CR than in those without monthly CR (2.3 ± 0.4 vs. -0.1 ± 0.3 points; p <0.001). Among the MMSE items, the change in temporal orientation and attention and calculation was significantly greater in the monthly CR group than in the non-monthly CR group (0.8 ± 0.7 vs. -0.1 ± 0.8 points [p <0.001] and 1.0 ± 1.5 vs. -0.1 ± 0.1 points [p <0.001], respectively). The general linear model revealed that monthly CR (effect estimate, 1.455; 95% confidence interval, 0.747-2.163; p <0.001) was independently associated with the change in the MMSE score. CONCLUSIONS: Cognitive function may improve with regular CR. These results might partly explain the efficacy of CR for secondary prevention.

Physical exertion as a trigger of acute coronary syndrome caused by plaque erosion.

Distinct clinical characteristics have been demonstrated in patients with plaque erosion as compared with those with plaque rupture. We reasoned that greater physical activity might influence the onset of plaque erosion. In total, 97 consecutive patients with non ST-segment elevation acute coronary syndrome (ACS) who underwent optical coherence tomography (OCT) imaging of the culprit lesion were enrolled. OCT-determined culprit plaque characteristics were plaque erosion (18.6%), calcified plaque (26.8%), plaque rupture (32.0%) and other (22.7%). The physical activity evaluated by estimated metabolic equivalents (METs) at ACS onset was significantly greater in the plaque erosion group than in the plaque rupture group (3.3 ± 1.7 vs. 2.1 ± 1.0, p = 0.011). The rate of ACS onset outdoors was the highest (61.1%) in the plaque erosion group. The combination of greater physical activity (> 3 METs), outdoor onset and higher body mass index (> 25.1 kg/m2) had a significant odds ratio for the incidence of plaque erosion (odds ratio 15.0, 95% confidence interval 3.81 to 59.0, p < 0.001). Plaque erosion was associated with greater physical activity at the onset. This finding may help to further clarify the pathogenesis of ACS Impact of physical exertion on the incidence of plaque erosion. NSTE-ACS, non ST-segment elevation acute coronary syndrome.

Age- and Gender-Related Differences in Coronary Lesion Plaque Composition on Optical Coherence Tomography.

BACKGROUND: The pathophysiology and chronological course of atherosclerosis seems to be different between men and women due to biological differences, and age and gender differences in plaque composition of coronary lesions remain to be elucidated.Methods and Results:A total of 860 consecutive patients with a median age of 69 years (IQR, 60-78 years) who underwent optical coherence tomography (OCT) of culprit lesions was included. The composition of culprit plaque on OCT was compared between female (n=171) and male (n=689) subjects in younger (<70 years old) and elderly (≥70 years old) patients. In elderly patients, the prevalence of thin-cap fibroatheroma (TCFA) was significantly higher in women than in men (30.6 vs. 15.2%, P<0.001). In younger patients, the prevalence of large calcification was significantly higher in women than in men (60.0 vs. 32.8%, P<0.001). The prevalence of other vulnerable plaque characteristics (i.e., macrophages, microchannels, and spotty calcification), was similar between women and men. Elderly women had a significantly higher prevalence of TCFA (OR, 2.13; 95% CI: 1.33-3.44, P=0.002) than other patients. CONCLUSIONS: Women had a higher prevalence of TCFA and of large calcification than men in patients ≥70 and <70 years old, respectively. This may facilitate the understanding of gender differences in the pathogenesis of coronary atherosclerosis, and the tailoring of therapy and of prevention according to age and gender.

Contrast Volume and Decline in Kidney Function in Optical Coherence Tomography-Guided Percutaneous Coronary Intervention.

Optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) may increase contrast volume. However, the impact of OCT-guided PCI on the decline in kidney function (DKF) in actual clinical practice remains unclear.Among 1,003 consecutive patients who underwent either OCT-guided or intravascular ultrasound (IVUS)-guided PCI in our institute, we identified 202 propensity score-matched pairs adjusted by baseline factors. The incidence of DKF was compared between the OCT-guided PCI group and the IVUS-guided PCI group. DKF was defined as an increase in serum creatinine level of ≥ 0.5 mg/dL or a relative increase of ≥ 25% over baseline within 48 hours (acute DKF) or 1 month (sustained DKF) after PCI.Baseline characteristics, including the prevalence of chronic kidney disease (54% versus 46%, P = 0.09), were comparable between the OCT- and IVUS-guided PCI groups except for the age. The contrast volume was comparable between the two groups (153 ± 56 versus 144 ± 60 mL, P = 0.09), although it was significantly greater in the OCT-guided PCI group in patients with acute coronary syndrome (ACS; 175 ± 55 versus 159 ± 43 mL, P = 0.04). The incidence of acute DKF (0.5% versus 2.5%, P = 0.22) and sustained DKF (5.0% versus 10.4%, P = 0.31) was comparable between the two groups. Multivariate analysis demonstrated that ACS (odds ratio 4.74, 95% confidence interval 2.72-8.25, P < 0.001) was a predictor of sustained DKF.Compared with IVUS-guided PCI, OCT-guided PCI did not increase the incidence of DKF in actual clinical practice, although the increased contrast volume was observed in ACS cases.

Acute Effects of Whole-Body Vibration Training on Endothelial Function and Cardiovascular Response in Elderly Patients with Cardiovascular Disease.

The aim of this single-arm pilot study was to determine the effects of whole-body vibration training (WBVT) on endothelial function in elderly patients with cardiovascular diseases, as well as its safety. A total of 20 elderly patients with stable cardiovascular diseases underwent WBVT, which consisted of five static resistance training exercises (squats, wide stance squats, toe-stands, squats + band, and front lunges). The parameters of WBVT included vertical vibrations, 30 Hz frequency, and a 3-mm peak-to-peak amplitude. Each vibration session lasted 30 seconds, with 120 seconds of rest between sessions. Before and after WBVT, the reactive hyperemia peripheral arterial tonometry index (RH-PAT index) and transcutaneous oxygen pressure (tcPO2) were recorded as a measure of endothelial function and peripheral blood circulation. Systolic blood pressure, diastolic blood pressure, heart rate, and arterial oxygen saturation of pulse oximetry (SpO2) were measured at each rest interval as well as before and after WBVT. All patients completed our WBVT protocol without adverse events. The RH-PAT index significantly increased following WBVT (1.42 to 2.06, P < 0.001). There were no significant changes in heart rate (P = 0.777), systolic blood pressure (P = 0.183), diastolic blood pressure (P = 0.925), or SpO2 (P = 0.248) during WBVT. In conclusion, we demonstrated the acute effects of WBVT on endothelial function, with no reports of adverse events. These findings support the need for further randomized controlled studies to investigate the long-term effects of WBVT.

Use of idarucizumab for dabigatran reversal in cardiac tamponade during atrial fibrillation ablation: A case report.

It is known that the efficacy of catheter ablation for atrial fibrillation (AF) is high, but cardiac tamponade may occur in 1-2% cases. Even in such cases, fatal condition can be avoided by appropriate drainage, but reversal of anticoagulation therapy might also be necessary. Here, we report a case of use of idarucizumab for cardiac tamponade during AF ablation. Although the drainage with pericardial centesis should be selected, we could not perform because echo free space was too thin at least at the precordial or apical side of the ventricle. Fortunately, dabigatran reversal by idarucizumab suppressed cardiac tamponade progress and the patient recovered without undergoing any invasive procedures. The pericardial drainage must be the principal therapy for cardiac tamponade, but reversal of anticoagulant might be helpful for patients' recovery. It might be thought that dabigatran, the only direct oral anticoagulant with a specific reversal agent, should be the safest choice in case of risk for bleeding complications such as AF ablation. .

Lipoprotein (a) level is associated with plaque vulnerability in patients with coronary artery disease: An optical coherence tomography study.

BACKGROUND: High lipoprotein (a) [Lp(a)] levels are an independent factor for worse prognosis in patients with coronary artery disease (CAD). However, the association between serum Lp(a) level and coronary plaque vulnerability remains to be determined. METHODS: A total of 255 consecutive patients with CAD who underwent optical coherence tomography imaging of culprit lesions were included. Patients were divided into 2 groups according to their Lp(a) levels (the higher Lp(a) group [≥25 mg/dL], n = 87; or the lower Lp(a) group [<25 mg/dL], n = 168). RESULTS: The prevalence of thin-cap fibroatheroma (TCFA) was significantly higher in the higher Lp(a) group than in the lower Lp(a) group (23% [n = 20] vs. 11% [n = 19], p = 0.014). Although the prevalence of TCFA was comparable between the 2 groups among patients with a lower LDL cholesterol (LDL-C) level (<100 mg/dL), TCFA was significantly more prevalent in the higher Lp(a) group than in the lower Lp(a) group (39% [14/36] vs. 10% [5/50], p = 0.001) among patients with a higher LDL-C level (≥100 mg/dL). CONCLUSIONS: A higher Lp(a) level was associated with a higher frequency of TCFA, particularly in patients with a higher LDL-C level.

Impaired Flow-Mediated Dilation and Severity and Vulnerability of Culprit Plaque in Patients with Coronary Artery Disease.

The association between endothelial function, evaluated using flow-mediated dilatation (FMD), and the severity of coronary artery disease remains to be elucidated.A total of 245 consecutive patients with stable angina were prospectively enrolled. FMD was evaluated in the brachial artery before percutaneous coronary intervention. Patients were divided into 2 groups according to the FMD value (lower FMD group [FMD < 2.0], n = 82; higher FMD group [FMD ≥ 2.0], n = 163). The severity of coronary artery disease was evaluated using findings of angiography and optical coherence tomography, and compared between the 2 groups.The prevalence of left main (LM) disease was significantly higher in the lower FMD group than in the higher FMD group (8.5% versus 2.5%, P = 0.046), although the prevalence of multivessel disease was comparable between the groups. Lower FMD was independently associated with a higher prevalence of LM disease (odds ratio, 3.89; 95% confidence interval, 1.12-15.5; P = 0.033). A general linear model with multiple variables revealed that the minimal lumen area (MLA) in the culprit lesion was significantly smaller in patients with lower FMD than in those with higher FMD (regression coefficient b, -0.249 mm2; 95% confidence interval, -0.479--0.018 mm2; P = 0.035). The prevalence ofvulnerable plaque characteristics was comparable between the 2 groups.Patients with lower FMD had a higher incidence of LM disease and a smaller MLA in the culprit lesion. FMD may be a useful, noninvasive indicator for identifying patients with severe coronary artery disease.