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.

Feasibility of Short-Term Aggressive Lipid-Lowering Therapy with the PCSK9 Antibody in Acute Coronary Syndrome.

BACKGROUND: The guideline-recommended low-density lipoprotein cholesterol target level of <70 mg/dL may not be achieved with statin administration in some patients with acute coronary syndrome (ACS). Therefore, the proprotein convertase subtilisin-kexin type 9 (PCSK9) antibody can be added to high-risk patients with ACS. Nevertheless, the optimal duration of PCSK9 antibody administration remains unclear. METHODS AND RESULTS: Patients were randomized to receive either 3 months of lipid lowering therapy (LLT) with the PCSK9 antibody followed by conventional LLT (with-PCSK9-antibody group) or 12 months of conventional LLT alone (without-PCSK9-antibody group). The primary endpoint was the composite of all-cause death, myocardial infarction, stroke, unstable angina, and ischemia-driven revascularization. A total of 124 patients treated with percutaneous coronary intervention (PCI) were randomly assigned to the two groups (n = 62 in each). The primary composite outcome occurred in 9.7% and 14.5% of the patients in the with- and without-PCSK9-antibody groups, respectively (hazard ratio: 0.70; 95% confidence interval: 0.25 to 1.97; p = 0.498). The two groups showed no significant differences in hospitalization for worsening heart failure and adverse events. CONCLUSIONS: In ACS patients who underwent PCI, short-term PCSK9 antibody therapy with conventional LLT was feasible in this pilot clinical trial. Long-term follow-up in a larger scale clinical trial is warranted.

Acute Myocardial Infarction Due to Coronary Artery Embolism during Chemotherapy with mFOLFOX-6 Plus Bevacizumab for Metastatic Colon Cancer.

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, may be associated with arterial embolisms. We herein report a case of acute myocardial infarction caused by coronary embolism during combination chemotherapy with mFOLFOX-6 and bevacizumab in a patient with metastatic colon cancer. Thromboembolism occurred only in the distal right posterolateral branch without stenotic lesions or plaque rupture in the proximal branch of the right coronary artery. Sole thromboaspiration was successfully performed; the final angiogram demonstrated no stenosis in the right coronary artery. Bevacizumab may be associated with acute coronary syndrome in patients with coronary risk factors, despite no significant coronary narrowing.

Subclinical and latent cardiac dysfunction in obstructive sleep apnea and effectiveness of continuous positive airway pressure.

PURPOSE: Obstructive sleep apnea (OSA) is associated with various cardiovascular disorders. This study aimed to investigate the effects of OSA on left ventricular (LV) function in patients with OSA who were at risk for heart failure but who had not yet developed structural heart changes. The study also sought to determine the effects of continuous positive airway pressure (CPAP) in these patients. METHODS: In a retrospective study, consecutive patients with polysomnographic OSA (apnea-hypopnea index [AHI] >5) were categorized into mild (AHI < 15), moderate (15 ≤ AHI < 30), and severe OSA (AHI ≥ 30) groups. The subjects were patients with OSA and at risk for heart failure who had not yet developed structural heart changes. All study participants underwent echocardiography and two-dimensional speckle tracking analysis, and their global longitudinal strain (GLS) was calculated. RESULTS: Of 275 patients, there were 31 with mild, 92 with moderate, and 152 with severe OSA. Of patients with moderate to severe OSA (AHI ≥ 20), 206 started CPAP and 92 patients underwent follow-up echocardiogram and speckle tracking echo analysis (median period of CPAP use: 283 days [258 to 391]). GLS was significantly reduced in patients with moderate and severe OSA compared with mild OSA (-17.8±3.1 vs. -18.0±2.6 vs. -19.3±2.8%, p=0.038). The proportion of patients with GLS ≥ -18% was significantly higher among the patients with moderate to severe OSA than among those with mild OSA. GLS improved after CPAP therapy in patients with moderate to severe OSA (GLS: -18.1±2.7% to -19.0±2.8%, p=0.004). Significant improvement in GLS was confirmed, particularly among patients with good CPAP adherence. CONCLUSION: Moderate to severe OSA is associated with LV dysfunction and can be significantly improved by CPAP therapy.

Emergency Transcatheter Aortic Valve Implantation in a Surgical Aortic Bioprosthetic Valve for Acute Decompensated Heart Failure Caused by Sudden Progression of Structural Valve Deterioration.

Bioprosthetic aortic valves have limited durability. We herein report sudden progression of structural valve deterioration (SVD) and a successful case of emergency transcatheter aortic valve (TAV) implantation for acute decompensated heart failure (ADHF) caused by SVD. A 79-year-old man who had undergone a Bentall operation 11 years prior was diagnosed with ADHF due to suddenly progressive SVD. Emergency TAV implantation in the surgical bioprosthetic valve was selected based on the surgical risk. Ours and previous case reports suggest that SVD can progress suddenly, even after months of stability, and that emergency TAV implantation is effective.

Serial changes of myocardial perfusion imaging in takotsubo and reverse takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TTC) shows reversible hypokinesis in the left ventricular (LV) apical-half segment and hyperkinesis in the LV basal-half segment. However, the precise pathophysiological mechanism of TTC is unclear. Therefore, this study sought to clarify the nuclear characteristics, degree of myocardial damage, and serial change of TTC and rTTC using myocardial perfusion imaging. METHODS: We performed myocardial perfusion scintigraphy in 28 patients (TTC: 20, rTTC: 8) using Tc-99m sestamibi and assessed minimum percentage uptake (min-%-uptake), extent score (ES) and summed rest score (SRS) at acute and chronic phases. RESULTS: Min-%-uptake improved from the acute to the chronic phase (TTC: 54 [48-59]% vs 87 [81-90]%, P  < 0.01; rTTC: 60 [55-64]% vs 77 [71-79]%, P < 0.01), as did the ES (TTC: 32 [26-41]% vs 0.0 [0.0-6.0]%, P < 0.01; rTTC: 16 [12-34]% vs 0.0 [0.0-0.0]%, P = 0.02) and SRS (TTC: 4.5 [3.9-5.3] vs 0.0 [0.0-0.2], P < 0.01; rTTC: 3.6 [3.3-3.8] vs 0.0 [0.0-0.0], P = 0.01). CONCLUSION: Tc-99m sestamibi uptake was reduced in hypokinetic regions in the acute phase and improved in the chronic phase. TTC and rTTC may involve a reversible disorder of the myocardial cell membrane, mitochondria, and microcirculation.

Difficulty Diagnosing Retrograde Type A Aortic Dissection with Intramural Hematoma and Risk of Re-dissection and Rupture: A Report of Two Cases.

Acute type A aortic dissection is a potentially fatal disease, and emergency surgery should be considered when it is diagnosed. We herein report two cases of retrograde type A aortic dissection with intramural hematoma, followed by re-dissection, rupture, and cardiac tamponade. The diagnoses in these cases had to be made carefully, as the false lumen of the ascending aorta was sometimes unclear on contrast-enhanced computed tomography.

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.

The Diagnosis of Spontaneous Coronary Artery Dissection by Optical Coherence Tomography.

Spontaneous coronary artery dissection (SCAD) is rare, but it frequently presents as acute myocardial infarction. It is frequently fatal and most cases are diagnosed at autopsy. We herein present the case of a 65-year-old woman with ST-elevation and myocardial infarction due to SCAD. Optical coherence tomography (OCT) helped us to confirm the diagnosis. The information on the intravascular morphology provided by OCT imaging is much more detailed in comparison to that provided by coronary angiography (CAG) and intravascular ultrasound (IVUS).

Functional, morphological and electrocardiographical abnormalities in patients with apical hypertrophic cardiomyopathy and apical aneurysm: correlation with cardiac MR.

OBJECTIVE: The prognosis of apical hypertrophic cardiomyopathy (APH) has been benign, but apical myocardial injury has prognostic importance. We studied functional, morphological and electrocardiographical abnormalities in patients with APH and with apical aneurysm and sought to find parameters that relate to apical myocardial injury. STUDY DESIGN: a multicentre trans-sectional study. PATIENTS: 45 patients with APH and 5 with apical aneurysm diagnosed with transthoracic echocardiography (TTE) in the database of Hamamatsu Circulation Forum. MEASURE: the apical contraction with cine-cardiac MR (CMR), the myocardial fibrotic scar with late gadolinium enhancement (LGE)-CMR, and QRS fragmentation (fQRS) defined when two ECG-leads exhibited RSR's patterns. RESULTS: Cine-CMR revealed 27 patients with normal, 12 with hypokinetic and 11 with dyskinetic apical contraction. TTE misdiagnosed 11 (48%) patients with hypokinetic and dyskinetic contraction as those with normal contraction. Apical LGE was apparent in 10 (83%) and 11 (100%) patients with hypokinetic and dyskinetic contraction, whereas only in 11 patients (41%) with normal contraction (p<0.01). Patients with dyskinetic apical contraction had the lowest left ventricular ejection fraction, the highest prevalence of ventricular tachycardia, and the smallest ST depression and depth of negative T waves. The presence of fQRS was associated with impaired apical contraction and apical LGE (OR=8.32 and 8.61, p<0.05). CONCLUSIONS: CMR is superior to TTE for analysing abnormalities of the apex in patients with APH and with apical aneurysm. The presence of fQRS can be a promising parameter for the early detection of apical myocardial injury.

Distribution of late gadolinium enhancement in end-stage hypertrophic cardiomyopathy and dilated cardiomyopathy: differential diagnosis and prediction of cardiac outcome.

BACKGROUND: The prognostic implications of late gadolinium enhancement (LGE) have been evaluated in ischemic and non-ischemic cardiomyopathies. The present study analyzed LGE distribution in patients with end-stage hypertrophic cardiomyopathy (ES-HCM) and with dilated cardiomyopathy (DCM), and tried to identify high risk patients in DCM. METHODS: Eleven patients with ES-HCM and 72 with DCM underwent cine- and LGE-cardiac magnetic resonance and ultrasound cardiography. The patient outcome was analyzed retrospectively for 5years of follow-up. RESULTS: LGE distributed mainly in the inter-ventricular septum, but spread more diffusely into other left ventricular segments in patients with ES-HCM and in a certain part of patients with DCM. Thus, patients with DCM can be divided into three groups according to LGE distribution; no LGE (n=24), localized LGE (localized at septum, n=36), and extensive LGE (spread into other segments, n=12). Reverse remodeling occurred after treatment in patients with no LGE and with localized LGE, but did not in patients with extensive LGE and with ES-HCM. The event-free survival rate for composite outcome (cardiac death, hospitalization for decompensated heart failure or ventricular arrhythmias) was lowest in patients with extensive LGE (92%, 74% and 42% in no LGE, localized LGE, and extensive LGE, p=0.02 vs. no LGE), and was comparable to that in patients with ES-HCM (42%). CONCLUSIONS: In DCM, patients with extensive LGE showed no functional recovery and the lowest event-free survival rate that were comparable to patients with ES-HCM. The analysis of LGE distribution may be valuable to predict reverse remodeling and to identify high-risk patients.

Evaluation of right and left ventricular function by quantitative blood-pool SPECT (QBS): comparison with conventional methods and quantitative gated SPECT (QGS).

Though quantitative ECG-gated blood-pool SPECT (QBS) has become a popular tool in research settings, more verification is necessary for its utilization in clinical medicine. To evaluate the reliability of the measurements of left and right ventricular functions with QBS, we performed QBS, as well as first-pass pool (FPP) and ECG-gated blood-pool (GBP) studies on planar images in 41 patients and 8 healthy volunteers. Quantitative ECG-gated myocardial perfusion SPECT (QGS) was also performed in 30 of 49 subjects. First, we assessed the reproducibility of the measurements of left and right ventricular ejection fraction (LVEF, RVEF) and left and right ventricular end-diastolic volume (LVEDV, RVEDV) with QBS. Second, LVEF and RVEF obtained from QBS were compared with those from FPP and GBP, respectively. Third, LVEF and LVEDV obtained from QBS were compared with those from QGS, respectively. The intra- and inter-observer reproducibilities were excellent for LVEF, LVEDV, RVEF and RVEDV measured with QBS (r = 0.88 to 0.96, p < 0.01), while the biases in the measurements of RVEF and RVEDV were relatively large. LVEF obtained from QBS correlated significantly with those from FPP and GBP, while RVEF from QBS did not. LVEF and LVEDV obtained from QBS were significantly correlated with those from QGS, but the regression lines were not close to the lines of identity. In conclusion, the measurements of LVEF and LVEDV with QBS have good reproducibility and are useful clinically, while those of RVEF and RVEDV are less useful compared with LVEF and LVEDV. The algorithm of QBS for the measurements of RVEF and RVEDV remains to be improved.

[Usefulness of lung and right ventricular thallium-201 uptake during single photon emission computed tomography in exercise testing of patients with coronary artery disease].

OBJECTIVES: Increased pulmonary or right ventricular 201Tl uptake during the exercise test has been used as a marker of multivessel coronary artery disease. The most useful method for assessing the severity of coronary artery disease was evaluated among conventional evaluation of single photon emission computed tomography (SPECT), measurement of lung to heart uptake ratio (L/H), and right ventricular to left ventricular uptake ratio (RV/LV) on 201Tl images during exercise testing. METHODS: Regions-of-interest (4 X 4 pixels) were placed at the lung and the heart, and L/H was defined as mean lung uptake/mean heart uptake. Correspondingly, regions-of-interest (4 X 4 pixels) were placed at the RV and the LV, and RV/LV was defined as maximum RV uptake /maximum LV uptake. L/H and RV/LV on the initial image were analyzed in 216 patients(angiographically normal coronary arteries: 89, single-vessel disease: 82, multivessel disease: 45). The diagnostic value was evaluated using the receiver operating characteristic curve. RESULTS: All methods showed significantly higher values in patients with multivessel disease than in patients with no coronary artery disease or single-vessel disease. L/H was significantly higher in patients with prior myocardial infarction and RV/LV was significantly higher in patients without infarction. The sensitivity of only conventional SPECT evaluation for multivessel coronary artery disease was low (sensitivity 53%, specificity 94%). However, addition of evaluation of L/H and RV/LV to SPECT improved the sensitivity for multivessel coronary artery disease (sensitivity 93%, specificity 49%). CONCLUSIONS: The diagnostic sensitivity for multivessel coronary artery disease was improved by adding L/H and RV/LV to conventional evaluation of exercise 201Tl SPECT. L/H and RV/LV during exercise 201Tl imaging may provide additional information regarding the severity of coronary artery disease.

Spontaneous multiple arterial dissections presenting with renal infarction and subarachnoid hemorrhage in a patient under treatment for infertility.

A 36-year-old woman developed multiple spontaneous arterial dissections in both renal arteries, the carotid artery, superior mesenteric artery, and vertebral artery, but not the aorta, and she suffered a renal infarction and subarachnoid hemorrhage within a short period of time. She had been undergoing frequent injections of human chorionic gonadotropin and human menopausal gonadotropin, together with oral estrogen therapy, during a 5-year infertility treatment regimen. As she had no other history of any disorder affecting the arterial walls, this therapy is suspected to have caused the multiple arterial deformities. Although cases of isolated arterial dissection are occasionally reported, it is rare for multiple dissections and serious symptoms to occur simultaneously.

Usefulness of stress myocardial perfusion imaging for evaluating asymptomatic patients after coronary stent implantation.

BACKGROUND: Stent implantation in coronary angioplasty has reduced the rate of restenosis, but many patients still undergo follow-up coronary angiography (CAG). The present study was a multi-center retrospective analysis of the usefulness of stress single photon emission computed tomography (SPECT) compared with follow-up CAG in stent-implanted patients who remained asymptomatic during the follow-up period. METHODS AND RESULTS: The study group of 103 patients underwent both SPECT and CAG at 4-9 months after stent implantation. Restenosis occurred in 20 (19%) of 106 vessel territories, and a reversible perfusion defect was found in 32 (30%) territories. Sensitivity, specificity, positive and negative predictive values, and accuracy of SPECT were 65%, 78%, 41%, 91%, and 76%, respectively. The accuracy was lower in territories with a prior myocardial infarction (71%), in the left circumflex artery (58%), and in cases with three-vessel disease (63%). The negative predictive value was high, but 7 false negative cases included 4 cases with prior myocardial infarction, and 2 cases with reversible defects in other vessel territories. CONCLUSIONS: Stress SPECT imaging is a useful tool for following up patients with coronary stent implantation, and follow-up CAG could be omitted in patients with negative SPECT imaging, no prior myocardial infarction, one- or two-vessel disease, and sufficient stress loading.