ISSN 1671-5411 CN 11-5329/R

2021 Vol. 18, No. 12

RESEARCH ARTICLE
A different cardiac resynchronization therapy technique might be needed in some patients with nonspecific intraventricular conduction disturbance pattern
Gábor Katona, Zsuzsanna Szelényi, Gábor Szénási, Bálint Kozman, Zsolt Rekvényi, Luca Kópházi, Zsolt Dobos, Szilvia Vereckei, András Vereckei
2021, 18(12): 975-985. doi: 10.11909/j.issn.1671-5411.2021.12.002
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Abstract:
 BACKGROUND  Current cardiac resynchronization therapy (CRT), devised to eliminate dyssynchrony in left bundle branch block (LBBB), works by pacing the latest activated left ventricular site (LALVS). We hypothesized that patients with nonspecific intraventricular conduction disturbance (NICD) pattern respond less favorably to CRT, because their LALVS is far away from that in LBBB.  METHODS  By measuring the amplitude and polarity of secondary ST-segment alterations in two optional frontal and horizontal surface electrocardiogram (ECG) leads and using a software, we determined the resultant 3D spatial secondary ST vector, which is directed 180o away from the LALVS, in 110 patients with LBBB pattern and 77 patients with NICD pattern and heart failure. To validate the ECG method, we also estimated the LALVS by echocardiography using 3D parametric imaging and 2D speckle tracking in 22 LBBB patients and 20 NICD patients. Patients with NICD pattern were subdivided according to their non-overlapping frontal plane resultant secondary ST vector ranges to the NICD-1 subgroup (n = 44) and the NICD-2 subgroup (n = 33). RESULTS  Based on the software determined coordinates of the resultant 3D spatial secondary ST vector directed 180o away from the LALVS, the LALVSs were located leftward, posterosuperior in the LBBB group, slightly left, superior in the NICD-1 subgroup, and slightly left, posteroinferior in the NICD-2 subgroup. The LALVS determined by ECG and echocardiography matched in all patients, except two.  CONCLUSIONS  In the NICD-2 subgroup, a remote LALVS was found from that in LBBB pattern, which might explain the high non-response rate of the NICD pattern to the current CRT technique.
Association between serum cystatin C level and hemodynamically significant aortic stenosis: a prospective cohort study
Odong Christopher, Xing-Feng XU, Yi-Fen LIN, Shao-Zhao ZHANG, Yi-Quan HUANG, Xiang-Bin ZHONG, Zhen-Yu XIONG, Tara Scarlett Rosalyn CHEN, Chao-Guang XU, Xiao-Dong ZHUANG, Xin-Xue LIAO
2021, 18(12): 986-995. doi: 10.11909/j.issn.1671-5411.2021.12.003
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Abstract:
 BACKGROUND  Cystatin C (CysC) is a cysteine protease inhibitor involved in proteins catabolism and plays an essential role in human vascular pathophysiology. CysC may also increase the risk of aortic stenosis (AS), but limited studies have reported on this association. This study aimed to investigate if elevated serum CysC levels are associated with hemodynamically significant AS.  METHODS  Serum CysC levels were estimated in 4,791 participants, samples were collected in 1990−1992. The study population was divided into quintile groups. Follow-up continued in 2011–2013 when participants returned for echocardiography examination. Incidence of aortic valve disease (AVD) was ascertained by Doppler echocardiography through the end of 2013. AVD defined in hemodynamic progression was assessed and classified as aortic sclerosis, mild stenosis, and moderate-to-severe stenosis.  RESULTS  Overall, a total of 4,791 participants (mean age: 54.8 ± 5.0 years, females: 57.6%, blacks: 8.2%) were included in this study. During a follow-up of 21 years, we identified 736 cases (15.4%) of aortic sclerosis, 194 cases (4.0%) of mild stenosis, and 42 cases (0.7%) of moderate-to-severe stenosis. Compared with serum CysC levels within individual quintile groups, the odds ratio (OR) was per standard deviation associated with an increased incidence of AVD (OR = 1.15, 95% CI: 1.05−1.26, P = 0.002).  CONCLUSIONS  In this large population-based study, an increased serum CysC levels is independently associated with the incidence of hemodynamically significant AS. However, this association appears not to extend to patients with extremely high serum CysC levels and necessitate further investigation.
Lipoprotein(a) is associated with coronary atheroma progression: analysis from a serial coronary computed tomography angiography study
Xi WANG, Dong-Kai SHAN, Guan-Hua DOU, Yi-Pu DING, Jing JING, He-Bin CHE, Jun-Jie YANG, Yun-Dai CHEN
2021, 18(12): 996-1007. doi: 10.11909/j.issn.1671-5411.2021.12.001
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Abstract:
 BACKGROUND  Lipoprotein(a) [Lp(a)] has been closely related to coronary atherosclerosis and might affect perivascular inflammation due to its proinflammatory properties. However, there are limited data about Lp(a) and related perivascular inflammation on coronary atheroma progression. Therefore, this study aimed to investigate the associations between Lp(a) and the perivascular fat attenuation index (FAI) with coronary atheroma progression detected by coronary computed tomography angiography (CCTA).  METHODS  Patients who underwent serial CCTA examinations without a history of revascularization and with available data for Lp(a) within one month before or after baseline and follow-up CCTA imaging scans were considered to be included. CCTA quantitative analyses were performed to obtain the total plaque volume (TPV) and the perivascular FAI. Coronary plaque progression (PP) was defined as a ≥ 10% increase in the change of the TPV at the patient level or the presence of new-onset coronary atheroma lesions. The associations between Lp(a) or the perivascular FAI with PP were examined by multivariate logistic regression.  RESULTS  A total of 116 patients were ultimately enrolled in the present study with a mean CCTA interscan interval of 30.80 ± 13.50 months. Among the 116 patients (mean age: 53.49 ± 10.21 years, males: 83.6%), 32 patients presented PP during the follow-up interval. Lp(a) levels were significantly higher among PP patients than those among non-PP patients at both baseline [15.80 (9.09−33.60) mg/dL vs. 10.50 (4.75−19.71) mg/dL, P = 0.029] and follow-up [20.60 (10.45−34.55) mg/dL vs. 8.77 (5.00−18.78) mg/dL, P = 0.004]. However, there were no differences in the perivascular FAI between PP group and non-PP group at either baseline or follow-up. Multivariate logistic regression analysis showed that elevated baseline Lp(a) level (OR = 1.031, 95% CI: 1.005−1.058, P = 0.019) was an independent risk factor for PP after adjustment for other conventional variables.  CONCLUSIONS  Lp(a) was independently associated with coronary atheroma progression beyond low-density lipoprotein cholesterol and other conventional risk factors. Further studies are warranted to identify the inflammation effect exhibited as the perivascular FAI on coronary atheroma progression.
Predictors of thirty-day readmission in nonagenarians presenting with acute heart failure with preserved ejection fraction: a nationwide analysis
Ahmed Maraey, Mahmoud Salem, Nabila Dawoud, Mahmoud Khalil, Ahmed Elzanaty, Hadeer Elsharnoby, Ahmed Younes, Ahmed Hashim, Amit Alam
2021, 18(12): 1008-1018. doi: 10.11909/j.issn.1671-5411.2021.12.005
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Abstract:
 BACKGROUD  Acute heart failure with preserved ejection fraction (HFpEF) is a common but poorly studied cause of hospital admissions among nonagenarians. This study aimed to evaluate predictors of thirty-day readmission, in-hospital mortality, length of stay, and hospital charges in nonagenarians hospitalized with acute HFpEF.  METHODS  Patients hospitalized between January 2016 and December 2018 with a primary diagnosis of diastolic heart failure were identified using ICD-10 within the Nationwide Readmission Database. We excluded patients who died in index admission, and discharged in December each year to allow thirty-day follow-up. Univariate regression was performed on each variable. Variables with P-value < 0.2 were included in the multivariate regression model.  RESULTS  From a total of 45,393 index admissions, 43,646 patients (96.2%) survived to discharge. A total of 7,437 patients (15.6%) had a thirty-day readmission. Mean cost of readmission was 43,265 United States dollars (USD) per patient. Significant predictors of thirty-day readmission were chronic kidney disease stage III or higher [adjusted odds ratio (aOR) = 1.20, 95% CI: 1.07−1.34, P = 0.002] and diabetes mellitus (aOR = 1.18, 95% CI: 1.07−1.29, P = 0.001). Meanwhile, female (aOR = 0.90, 95% CI: 0.82−0.99, P = 0.028) and palliative care encounter (aOR = 0.27, 95% CI: 0.21−0.34, P < 0.001) were associated with lower odds of readmission. Cardiac arrhythmia (aOR = 1.46, 95% CI: 1.11−1.93, P = 0.007) and aortic stenosis (aOR = 1.36, 95% CI: 1.05−1.76, P = 0.020) were amongst predictors of in-hospital mortality.  CONCLUSIONS  In nonagenarians hospitalized with acute HFpEF, thirty-day readmission is common and costly. Chronic comorbidities predict poor outcomes. Further strategies need to be developed to improve the quality of care and prevent the poor outcome in nonagenarians.
The influence of metabolic syndrome on atrial fibrillation recurrence: five-year outcomes after a single cryoballoon ablation procedure
Yu XIA, Xiao-Feng LI, Jun LIU, Miao YU, Pi-Hua FANG, Shu ZHANG
2021, 18(12): 1019-1028. doi: 10.11909/j.issn.1671-5411.2021.12.008
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Abstract:
 BACKGROUND  Metabolic syndrome (MetS) has been reported as a risk factor of atrial fibrillation (AF) recurrence after radiofrequency catheter ablation. This study aimed to investigate the long-term influence of MetS on paroxysmal AF recurrence after a single cryoballoon ablation procedure, which was scarcely investigated yet in Chinese population. METHODS  In total, 137 paroxysmal AF patients who had successfully completed a single cryoballoon ablation procedure at Fuwai Hospital, Beijing, China from December 2013 to October 2015 were enrolled. Excepting for patients with AF recurrence, all patients were followed up for no less than five years. Independent predictors of AF recurrence were determined by Cox proportional hazards regression analysis. RESULTS  Among 137 paroxysmal AF patients, 91 patients (66.4%) had successfully achieved overall five-year follow-up after a single cryoballoon ablation procedure, and 44 patients (32.1%) had MetS. Patients with MetS had a significant lower incidence of freedom from AF recurrence than those without MetS (50.0% vs. 74.2%, log-rank P < 0.01) during the five-year follow-up. MetS (HR = 1.95, 95% CI: 1.069−3.551, P = 0.030) was an independent predictor of AF recurrence after adjusting for multiple factors. After the second year post cryoballoon ablation procedure, the recurrence rate of AF gradually increased in patients with MetS, in contrast, decreased recurrence rate of AF in patients without MetS. CONCLUSIONS  MetS is an independent predictor for five-year AF recurrence after a single cryoballoon ablation procedure in paroxysmal AF patients. Combination therapy of AF and MetS may improve the long-term outcomes of AF patients.
MiR-21-5p-expressing bone marrow mesenchymal stem cells alleviate myocardial ischemia/reperfusion injury by regulating the circRNA_0031672/miR-21-5p/programmed cell death protein 4 pathway
Jing ZHANG, Chang-Jun LUO, Xiao-Qi XIONG, Jun LI, San-Hua TANG, Lin SUN, Qiang SU
2021, 18(12): 1029-1043. doi: 10.11909/j.issn.1671-5411.2021.12.004
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Abstract:
 BACKGROUND  For patients with coronary heart disease, reperfusion treatment strategies are often complicated by ischemia/reperfusion (I/R) injury (IRI), leading to serious organ damage and malfunction. The miR-21/programmed cell death protein 4 (PDCD4) pathway is involved in the IRI of cardiomyocytes; however, the aberrant miR-21 expression remains unexplained. Therefore, this study aimed to explore whether circRNA_0031672 downregulates miR-21-5p expression during I/R and to determine whether miR-21-5p-expressing bone marrow mesenchymal stem cells (BMSCs) reduce myocardial IRI. METHODS  CircRNA_0031672, miR-21-5p, and PDCD4 expressions were evaluated in the I/R rat model and hypoxia/re-oxygenation (H/R)-treated H9C2 cells. Their interactions were subsequently investigated using luciferase reporter and RNA pulldown assays. Methyltransferase-like 3, a methyltransferase catalyzing N6-methyladenosine (m6A), was overexpressed in H9C2 cells to determine whether m6A modification influences miR-21-5p targeting PDCD4. BMSCs stably expressing miR-21 were co-cultured with H9C2 cells to investigate the protective effect of BMSCs on H9C2 cells upon H/R. RESULTS  I/R downregulated miR-21-5p expression and upregulated circRNA_0031672 and PDCD4 expressions. CircRNA_0031672 knockdown increased miR-21-5p expression, but repressed PDCD4 expression, indicating that circRNA_0031672 competitively bound to miR-21-5p and prevented it from targeting PDCD4 mRNA. The m6A modification regulated PDCD4 expression, but had no effect on miR-21-5p targeting PDCD4. The circRNA_0031672/miR-21-5p/PDCD4 axis regulated myocardial cells viability and apoptosis after H/R treatment; co-culture with miR-21-5p-expressing BMSCs restored miR-21-5p abundance in H9C2 cells and further reduced H9C2 cells apoptosis induced by H/R. CONCLUSIONS  We identified a novel circRNA_0031672/miR-21-5p/PDCD4 signaling pathway that mediates the apoptosis of cardiomyocytes and successfully alleviates IRI in myocardial cells by co-culture with miR-21-5p-expressing BMSCs, offering novel insights into the IRI pathogenesis in cardiovascular diseases.
PERSPECTIVE
Energy metabolism homeostasis in cardiovascular diseases
Lu-Yun WANG, Chen CHEN
2021, 18(12): 1044-1057. doi: 10.11909/j.issn.1671-5411.2021.12.006
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Abstract:
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the general population. Energy metabolism disturbance is one of the early abnormalities in CVDs, such as coronary heart disease, diabetic cardiomyopathy, and heart failure. To explore the role of myocardial energy homeostasis disturbance in CVDs, it is important to understand myocardial metabolism in the normal heart and their function in the complex pathophysiology of CVDs. In this article, we summarized lipid metabolism/lipotoxicity and glucose metabolism/insulin resistance in the heart, focused on the metabolic regulation during neonatal and ageing heart, proposed potential metabolic mechanisms for cardiac regeneration and degeneration. We provided an overview of emerging molecular network among cardiac proliferation, regeneration, and metabolic disturbance. These novel targets promise a new era for the treatment of CVDs.
LETTER TO THE EDITOR
Echocardiography and impedance cardiography as determinants of successful slow levosimendan infusion in advanced older heart failure patients
Gaetano Ruocco, Guido Pastorini, Mauro Feola
2021, 18(12): 1058-1062. doi: 10.11909/j.issn.1671-5411.2021.12.010
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Reversible heart failure in a patient with hypocalcemic cardiomyopathy
Mehrdad Jafari Fesharaki, Nooshin Ahmadi, Kimia Karimi Taheri
2021, 18(12): 1063-1067. doi: 10.11909/j.issn.1671-5411.2021.12.009
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Takotsubo syndrome with underlying pheochromocytoma
Tooba Sahar, Asaad Akbar Khan, Raja Wajid Shabbir
2021, 18(12): 1068-1070. doi: 10.11909/j.issn.1671-5411.2021.12.007
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Abstract: