Machine learning-based detection of sleep-disordered breathing in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is often concomitant with sleep-disordered breathing (SDB), which can cause adverse cardiovascular events. Although an appropriate approach to SDB prevents cardiac remodelling, detection of concomitant SDB in patients with HCM remains suboptimal. Thus, we aimed to develop a machine learning-based discriminant model for SDB in HCM. METHODS: In the present multicentre study, we consecutively registered patients with HCM and performed nocturnal oximetry. The outcome was a high Oxygen Desaturation Index (ODI), defined as 3% ODI >10, which significantly correlated with the presence of moderate or severe SDB. We randomly divided the whole participants into a training set (80%) and a test set (20%). With data from the training set, we developed a random forest discriminant model for high ODI based on clinical parameters. We tested the ability of the discriminant model on the test set and compared it with a previous logistic regression model for distinguishing SDB in patients with HCM. RESULTS: Among 369 patients with HCM, 228 (61.8%) had high ODI. In the test set, the area under the receiver operating characteristic curve of the discriminant model was 0.86 (95% CI 0.77 to 0.94). The sensitivity was 0.91 (95% CI 0.79 to 0.98) and specificity was 0.68 (95% CI 0.48 to 0.84). When the test set was divided into low-probability and high-probability groups, the high-probability group had a higher prevalence of high ODI than the low-probability group (82.4% vs 17.4%, OR 20.9 (95% CI 5.3 to 105.8), Fisher's exact test p<0.001). The discriminant model significantly outperformed the previous logistic regression model (DeLong test p=0.03). CONCLUSIONS: Our study serves as the first to develop a machine learning-based discriminant model for the concomitance of SDB in patients with HCM. The discriminant model may facilitate cost-effective screening tests and treatments for SDB in the population with HCM.

Plasma Globotriaosylsphingosine Level as a Primary Screening Target for Fabry Disease in Patients With Left Ventricular Hypertrophy.

BACKGROUND: Although previous studies have suggested a certain prevalence of Fabry disease (FD) in left ventricular hypertrophy (LVH) patients, the screening of FD is difficult because of its wide-ranging clinical phenotypes. We aimed to clarify the utility of combined measurement of plasma globotriaosylsphingosine (lyso-Gb3) concentration and α-galactosidase A activity (α-GAL) as a primary screening of FD in unexplained LVH patients.Methods and Results:Between 2014 and 2016, both lyso-Gb3 and α-GAL were measured in 277 consecutive patients (male 215, female 62, age 25-79 years) with left ventricular wall thickness >12 mm on echocardiogram: 5 patients (1.8%) screened positive (2 (0.7%) showed high lyso-Gb3 and 4 (1.4%) had low α-GAL levels). Finally, 2 patients (0.7%) were diagnosed with clinically significant FD. In 1 case, a female heterozygote with normal α-GAL levels had genetic variants of unknown significance and was diagnosed as FD by endomyocardial biopsy. The other case was a male chronic renal failure patient requiring hemodialysis, and he had a p.R112H mutation. In both cases there were high lyso-Gb3 levels. CONCLUSIONS: The serum lyso-Gb3 level can be relevant for clinically significant FD, and combined measurement of lyso-Gb3 and α-GAL can provide better screening of FD in unexplained LVH patients.

Very late stent thrombosis occurring simultaneously in sirolimus-eluting stents and bare-metal stent in three different coronary vessels.

A 36-year-old male was diagnosed with acute inferior myocardial infarction (MI). Emergent coronary angiography (CAG) revealed an occlusive lesion in the distal segment of the right coronary artery (RCA). The proximal and distal sites of the lesion were treated with a bare-metal stent (BMS) and a sirolimus-eluting stent (SES), respectively. Nine days later, he underwent elective percutaneous coronary intervention (PCI). Two SESs were implanted for the stenotic lesion in the left anterior descending artery (LAD), in addition to one SES for the mid-stenotic lesion in the left circumflex artery (LCX). Nine months after PCI, follow-up CAG revealed no restenosis at any stent-implanted site. Two years and 4 months after PCI, he was admitted to our hospital because of acute anterior MI. Emergent CAG revealed total thrombotic occlusion in the in-stent proximal site of LAD. Moreover, thrombotic lesions were also observed in in-stent sites: in both BMS of RCA and SES of LCX. He underwent intracoronary aspiration thrombectomy and plain old balloon angioplasty for LAD using intra-aortic balloon pumping. PCI for the thrombotic lesions in RCA and LCX was not performed. Seventeen days after the stent thrombosis, CAG revealed the complete disappearance of thrombi in LAD, LCX, and RCA.

Giant coronary aneurysm in a patient with systemic lupus erythematosus.

Coronary aneurysm is rare in SLE and confirmation of etiology is usually made at postmortem examination. We encountered a giant aneurysm with multiple stenotic segments of the coronary arteries in a patient with SLE who had previous history of AAA/TAA. Resection of the aneurysm and coronary artery bypass graft were successfully performed. Histology of the coronary arterial wall showed severe damage of the media with inflammatory cell infiltration, indicating that the aneurysm was caused by arteritis. The aneurysm may have developed during the long course of inactive stage of SLE, emphasizing the need for screening of coronary lesions in the management of SLE.

Difference in the cardioprotective mechanisms between ischemic preconditioning and pharmacological preconditioning by diazoxide in rat hearts.

BACKGROUND: Recent studies have implicated the opening of mitochondrial K(ATP) (mitoK(ATP)) channels and the production of reactive oxygen species (ROS) in the cardioprotective mechanism of ischemic preconditioning (IPC). METHODS AND RESULTS: The involvement of mitoK(ATP) channels and ROS in the cardioprotective effects of both IPC and the mitoK(ATP) channel opener diazoxide (DZ) was investigated in ischemic/reperfused rat hearts. The effects of IPC and DZ on myocardial high-energy phosphate concentrations and intracellular pH (pH(i)) were also examined using (31)P nuclear magnetic resonance spectroscopy. Although both the mitoK(ATP) channel inhibitor 5-hydroxydecanoate and the antioxidant N-acetylcysteine abolished the postischemic recovery of contractile function by DZ, neither of them inhibited that by IPC. IPC attenuated the decline in pHi during ischemia, but DZ did not (6.28+/-0.04 in IPC, p<0.05, and 6.02+/-0.05 in DZ vs 6.02 +/-0.06 in control hearts). DZ, but not IPC, reduced the decrease in ATP levels during ischemia (ATP levels at 20-min ischemia: 26.3+/-3.4% of initial value in DZ, p<0.05, and 8.1+/-3.0% in IPC vs 15.1+/-1.3% in control hearts). CONCLUSIONS: These results suggest that DZ-induced cardioprotection is related to ROS production and reduced ATP degradation during ischemia, whereas attenuated acidification during ischemia is involved in IPC-induced cardioprotection, which is not mediated through mitoK(ATP) channel opening or ROS production.

Protective effects of hydrogen peroxide against ischemia/reperfusion injury in perfused rat hearts.

Among the several mechanisms proposed for ischemic preconditioning (IPC), generation of reactive oxygen species (ROS) is reported to be involved in the cardioprotective effects of IPC. The present study was designed to investigate whether repetitive exposure to hydrogen peroxide (H(2)O(2)) can protect the myocardium against subsequent ischemia/reperfusion injury, and whether the H(2)O(2)-induced cardioprotection is related to the preservation of energy metabolism. Langendorff-perfused rat hearts were exposed to two, 5 min episodes of IPC or to various concentrations of H(2)O(2) twice and then to 35 min global ischemia and 40 min reperfusion. Using (31)P nuclear magnetic resonance ((31)P-NMR) spectroscopy, cardiac phosphocreatine (PCr) and ATP and intracellular pH (pH(i)) were monitored. IPC and the treatment with 2 micromol/L H(2)O(2) significantly improved the post-ischemic recovery of left ventricular developed pressure (LVDP) and the PCr and ATP compared with those of the control ischemia/reperfusion (LVDP: 36.9 +/-7.4% of baseline in control hearts, 84.0+/-3.5% in IPC, 65.4+/-3.8% in H(2)O(2); PCr: 51.1+/-5.3% in control hearts, 81.4+/-5.5% in IPC, 81.7+/-5.2% in H(2)O(2); ATP: 12.3+/-1.6% in control hearts; 30.0+/-2.8% in IPC, 28.6+/-2.3% in H(2)O(2), mean +/- SE, p<0.05). However, lower (0.5 micromol/L) or higher (10 micromol/L) concentration of H(2)O (2) had no effect. There were significant linear correlations between mean LVDP and high-energy metabolites after 40 min reperfusion in H(2)O(2)-treated hearts. In IPC-treated hearts, the mean LVDP was greater than that in the 2 micromol/L H(2)O(2)-treated hearts under similar levels of high-energy metabolites. IPC also ameliorated intracellular acidification (6.38+/-0.03 in control hearts, 6.65+/-0.04 in IPC, p<0.05), but treatment with H(2)O(2) did not affect pH(i) during ischemia (6.40+/-0.05 in H(2)O(2)). In conclusion, H(2)O(2) had protective effects against ischemia/reperfusion injury and the effects were related to the preservation of energy metabolism. IPC could have additional protective mechanisms that are associated with the amelioration of intracellular acidosis during ischemia.