Red cell distribution width as a prognosticator in patients with heart failure.

AIMS: Increased red cell distribution width (RDW) is a poor prognostic factor in patients with heart failure (HF). However, only a few large-scale studies have identified the clinical utility of RDW after adjusting for covariates affecting RDW. METHODS AND RESULTS: From January 2010 to April 2021, we retrospectively enrolled patients diagnosed with HF from three referral hospitals with available RDW data (taken within 3 months of HF diagnosis) using an integrated clinical data system. Patients with an ejection fraction (EF) < 50% or HFA-PEFF (Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final aetiology) score ≥ 2 without severe valvular heart disease or coronary revascularization were enrolled. The primary endpoint was all-cause mortality, and cardiovascular mortality was also collected. Multivariable Cox regression analysis and stabilized inverse probability of treatment weighting (IPTW) were used to identify any association between RDW and all-cause death by balancing covariates or compounding factors. The global χ2 score was calculated and discrimination analysis was performed to evaluate the incremental value of RDW in predicting prognosis. Among the 6599 participants enrolled in this study, 1256 (19.0%) cases of all-cause death occurred, and the median duration of follow-up was 887 (interquartile range 351-1589) days. Elevated RDW at the initial diagnosis was associated with poor prognosis [cumulative incidence: 819 (30.2%) vs. 437 (11.2%), relative risk 1.58, 95% confidence interval (CI) 1.51-1.67, log-rank P < 0.001]. Multivariable Cox analysis showed that elevated RDW was a poor prognostic factor for the primary endpoint [hazard ratio (HR) 1.11, 95% CI 1.06-1.16, P < 0.001], independent of clinical risk factors, N-terminal pro-brain natriuretic peptide (NT-proBNP), and EF, which was concordant with the stabilized IPTW (HR 1.29, 95% CI 1.10-1.49, P < 0.001). Adding RDW to model composed of traditional risk factors, NT-proBNP, and echocardiographic parameters showed incremental prognostic value for predicting poor prognosis (area under the receiver operating characteristic curve, 0.799-0.826; P < 0.001). CONCLUSIONS: Increased RDW at the time of diagnosis is associated with poor prognosis in patients with HF, independent of clinical risk factors, such as NT-proBNP, and echocardiographic parameters. Therefore, RDW may aid in the management of these patients beyond traditional risk factors.

Effects of left atrial function on pulmonary arterial pressure in acute myocardial infarction, hypertrophic and dilated cardiomyopathy.

BACKGROUND: To investigate the differential contribution of the left atrial (LA) function and left ventricular (LV) fibrosis to pulmonary arterial systolic pressure (PASP) in hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and reperfused acute myocardial infarction (AMI). METHODS: Data of 370 patients with HCM (n = 133), DCM (n = 114) and reperfused AMI (n = 123) who underwent both echocardiography and cardiovascular magnetic resonance (CMR) were comprehensively reviewed. Phasic LA volumes, LA-global longitudinal strain (GLS), LA stiffness index, defined as E/e'/LA-GLS and extracellular volume fraction (ECV) of LV were measured using CMR. RESULTS: E/e' was correlated with PASP in all groups; however, the predicted value was significantly attenuated after adjusting for LA volume and LA strain in HCM and DCM, but remained significant in AMI. The LA stiffness index was related to PASP in HCM (p = 0.01) and DCM (p = 0.03) independent of LA volume index and E/e', but not in AMI. In DCM, ECV was significantly related to PASP (p < 0.001) independent of LA volume index and E/e'. When subdivided according to the linear regression between PASP and E/e', patients in the discrepantly high PASP group had lower total emptying fraction and reservoir fraction of left atrium in HCM and DCM but not in AMI. CONCLUSIONS: The LA function in HCM and DCM and LV fibrosis in DCM correlated with PASP independent of E/e' and LA size, contrary to that in AMI. These results suggest the presence of LA dysfunction in non-ischemic cardiomyopathies and usefulness of ECV measurement in DCM for the comprehensive evaluation of LV diastolic function.

Central hemodynamics and the discrepancy between central blood pressure and brachial blood pressure.

Despite similar brachial blood pressure, central hemodynamics could be different. The objective of the present study was to investigate the factors, which could influence the discrepancy between central BP (cBP) and brachial blood pressure. Six hundred forty-seven patients (364 males, 48 ± 12 years old) were enrolled. Using applanation tonometry, cBP was noninvasively derived. The median difference between brachial systolic BP (bSBP) and central systolic BP (cSBP) was 8 mm Hg. We defined the discrepancy between bSBP and cSBP as differences >8 mm Hg. For adjustment of cBP, population was divided into 3 groups according to the cBP: group 1, <140 mm Hg of cSBP; group 2, 140 > cSBP < 160 mm Hg; group 3, =160 mm Hg of cSBP. All the central hemodynamic parameters of the patients, including augmentation pressure, augmentation index (AI), heart rate (75 bpm) adjusted augmentation index (AI@HR75), and subendocardial viability ratio, were measured. Using multivariate logistic regression analysis, we evaluated the factors which could influence the discrepancy between bSBP and cSBP. Age, gender, augmentation pressure, AI, and AI@HR75 were correlated with the discrepancy between bSBP and cSBP. AI@HR75 was significantly correlated with the discrepancy between bSBP and cSBP (ß-coefficient = -0.376, P < .001 in group 1; ß-coefficient = -0.297, P < .001 in group 2; and ß-coefficient = -0.545, P < .001 in group 3). In groups 1 and 2, male gender was significantly correlated with the discrepancy between bSBP and cSBP (ß-coefficient = -0.857, P = .035 in group 1; ß-coefficient = -1.422, P = .039 in group 2). In present study, arterial stiffness might affect the discrepancy between bSBP and cSBP. Also, male gender was closely related to the discrepancy between bSBP and cSBP especially with cSBP <160 mm Hg. Not only cSBP, the discrepancy between cSBP and bSBP should be considered for understanding the central hemodynamics.

Associations between Subclinical Myocardial Dysfunction and Premature Fusion of Early and Late Diastolic Filling with Uncertain Cause.

PURPOSE: The fusion of early (E) and late diastolic filling (A) on mitral inflow Doppler, even in the absence of tachycardia, is often found during assessment of left ventricular (LV) diastolic function. We evaluated the echocardiographic characteristics and clinical implications of premature E-A fusion of uncertain cause in the absence of tachycardia. MATERIALS AND METHODS: We identified 1014 subjects who showed E-A fusion and normal LV ejection fraction (LVEF) between January 2019 and June 2021 at two tertiary hospitals. Among these, 105 (10.4%) subjects showed premature E-A fusion at heart rates less than 100 beats per minute (bpm). The conventional echocardiographic parameters and LV global longitudinal strain (GLS) were compared with 1:1 age-, sex-, and heart rate-matched controls without E-A fusion. RESULTS: The premature E-A fusion group had a heart rate of 96.4±3.7 bpm. Only 4 (3.8%) subjects were classified as having LV diastolic dysfunction according to current guidelines. The group showed prolonged isovolumic relaxation time (107.2±25.3 msec vs. 61.6±15.6 msec, p<0.001), increased Tei index (0.76±0.19 vs. 0.48±0.10, p<0.001), lower LVEF (63.8±7.0% vs. 67.3±5.6%, p<0.001) and lower absolute LV GLS (|LV GLS|) (17.0±4.2% vs. 19.7±3.3%, p<0.001) than controls. As the E-A fusion occurred at lower heart rate, the |LV GLS| was also lower (p for trend=0.002). CONCLUSION: Premature E-A fusion at heart rates less than 100 bpm is associated with subclinical LV dysfunction. Time-based indices and LV GLS are helpful for evaluating this easily overlooked population.

The association between cardiac involvement and long-term clinical outcomes in patients with Duchenne muscular dystrophy.

AIMS: Despite advances in contemporary cardiopulmonary therapies, cardiomyopathy remains the leading cause of death in patients with Duchenne muscular dystrophy (DMD). Also, the long-term clinical outcomes of patients with DMD and cardiomyopathy is unknown. This study investigated long-term clinical outcomes and their associated factors in patients with late-stage DMD. METHODS AND RESULTS: A total of 116 patients with late-stage DMD (age > 15 years) were enrolled in this retrospective study. All enrolled patients were followed up at a single tertiary referral hospital. LV systolic dysfunction was dichotomously defined as reduced [left ventricular ejection fraction (LVEF) ≤ 40%] vs. preserved [>40%] based on the initial echocardiographic result. The primary endpoint was all-cause death. The secondary endpoint was a composite event defined as death or unexpected hospitalization due to cardiovascular reasons including chest pain, dyspnoea, and generalized oedema. The patients were divided into preserved (n = 84, 72.4%) and reduced LVEF groups (n = 32, 27.6%). The mean age was 20.8 ± 5.9 years, the mean disease duration, 8.8 ± 3.7 years, and the mean follow-up duration, 1708 ± 659 days. For primary endpoint, the reduced LVEF group showed a lower rate of overall survival (Reduced LVEF vs. Preserved LVEF; 81.3% vs. 98.8%, log-rank P = 0.005). In the multivariable Cox regression analysis, brain-natriuretic peptide (BNP) level (adjusted hazard ratio [HR] 1.088, 95% confidence interval [CI] 1.019-1.162, P = 0.011) and diuretic use (adjusted HR 9.279, 95%CI 1.651-52.148, P = 0.011) were significant predictors of all-cause death in patients with DMD. For the secondary endpoint, the reduced LVEF group had a lower rate of freedom from composite events than the preserved LVEF group (65.6% vs. 86.9%, log-rank P = 0.005). In the multivariable Cox regression analysis, BNP level (adjusted HR 1.057, 95%CI 1.005-1.112, P = 0.032) and diuretic use (adjusted HR 4.189, 95% CI 1.704-10.296, P = 0.002) were significant predictors of the composite event in patients with DMD. CONCLUSIONS: Patients with DMD and reduced LVEF had worse clinical outcomes than those with preserved LVEF. BNP level and diuretic use were associated with adverse clinical outcomes in patients with late-stage DMD, irrespective of LVEF.

Impact of aortic atheroma and distensibility on diastolic function and prognosis in patients with ischemic stroke.

BACKGROUND: Patients with ischemic stroke are vulnerable to heart failure with preserved ejection fraction (HFpEF) because these conditions share common risk factors. Although evaluation of the ascending aorta, aortic arch, and proximal descending thoracic aorta is an essential step to determine the source of the causative embolism, the relationship between the degree of aortic atheroma and left ventricular (LV) diastolic function has not been extensively investigated. METHODS: We analyzed the transesophageal and transthoracic echocardiography in ischemic stroke patients. Patients with previous coronary artery disease, valvular heart disease of more than moderate degree, and an LV ejection fraction of less than 50% were excluded. The relationships between the grade of the aortic atheroma, aortic stiffness indexes, and diastolic functional indexes were evaluated. RESULTS: In 295 patients, the atheroma grade was significantly correlated with aortic stiffness index, ratio of mitral annular and inflow velocities (E/e'), left atrial volume index, and LV diastolic elastance. With further adjustment for age, hypertension, diabetes, estimated glomerular filtration rate, left atrial volume index, and LV mass index, the significance of the atheroma grade was attenuated. In the subgroup analysis, the atheroma grade was significantly and independently related to E/e' in women (ß = 0.181, p = 0.032), but not in men. However, atheroma grade was not associated with poor clinical outcomes in either sex. CONCLUSIONS: Aortic atheroma grade was significantly and independently related to LV diastolic function, especially in women. This suggests that aortic atheroma is an index of arterial stiffness and a potential risk factor for HFpEF through ventricular-vascular interactions, especially in women.

Comparison of risk profiles for new-onset atrial fibrillation between patients aged <60 and ≥60 years.

BACKGROUND: Atrial fibrillation (AF) has a heterogeneous pathophysiology according to individual patient characteristics. This study aimed to identify the effects of widely known risk factors on AF incidence according to age and to elucidate the clinical implications of these effects. METHODS AND RESULTS: We analyzed data from 501,668 subjects (≥18years old) without AF and valvular heart disease from the Korean National Health Insurance Service-National Sample Cohort. The total population was divided into two groups according to age, <60years and ≥60years. AF occurred in 0.7% of the overall population (3,416 of 501,668) during the follow-up period (mean 47.6 months). In Cox regression analysis, age, male sex, previous ischemic stroke, heart failure, and hypertension were related to increased risk of new-onset AF in both age groups. Especially in the <60years age group, risk of new-onset AF was increased by relatively modifiable risk factors: obesity (body mass index ≥25kg/m2; hazard ratio[HR] 1.37 [1.22-1.55], p<0.001, interaction p<0.001), and hypertension (HR 1.93[1.69-2.22], p<0.001, interaction p<0.001). Although interactions were not significant, chronic obstructive pulmonary disease (HR 1.41[1.24-1.60], p<0.001) and chronic kidney disease (HR 1.28[1.15-1.41], p<0.001) showed increased trends of the risk of new-onset AF in the ≥60years age group. CONCLUSION: The risk profile for new-onset AF was somewhat different between the <60years and the ≥60years age groups. Compared to the ≥60years group, relatively modifiable risk factors (such as obesity and hypertension) had a greater impact on AF incidence in the <60years age group. Different management strategies to prevent AF development according to age may be needed.

Left ventricular outflow obstruction occurs immediately after exercise in patients with non-obstructive hypertrophic cardiomyopathy.

We evaluated the hemodynamic and geometric determinants of latent obstruction (LO, trans-left ventricular outflow tract (LVOT) gradient ≥30 mmHg with provocation) in patients with non-obstructive hypertrophic cardiomyopathy (HCMP). A total of 35 patients with non-obstructive HCMP underwent stepwise supine bicycle exercise echocardiography. Trans-LVOT pressure gradients, mitral geometric parameters, left ventricular ejection fractions (LVEF) and left ventricular end-systolic and diastolic dimensions (LVESD, LVEDD) were measured at each stage. The highest peak LVOT pressure gradient predominantly occurred immediately after exercise (n = 32, 91.3%) rather than during peak exercise (n = 3, 8.7%). Significant LO developed in nine patients (25%). No significant differences were found in resting echocardiographic parameters. Compared to the remaining patients, however, patients with LO had longer residual mitral leaflets (defined as residual portions of leaflets after coaptation; 4 ± 4 vs. 13 ± 4 mm, respectively; p = 0.001) and higher resting LVOT pressure gradients (7.4 ± 3.7 vs. 12.9 ± 5.8 mmHg, respectively; p = 0.001). Substantial decreases in mitral annular diameters from peak exercise to recovery after exercise were observed in the LO group, while mitral annular diameters increased after exercise in the non-LO group. In conclusion, the highest peak LVOT pressure gradient predominantly occurred immediately after exercise rather than during peak exercise, regardless of LO. Abrupt decrease of mitral annular diameter immediately after exercise, a longer residual mitral leaflet and a higher resting LVOT pressure gradient at rest might be related to LO.

Effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in patients with hypertrophic cardiomyopathy.

BACKGROUND: Myocardial fibrosis is an important prognostic factor in hypertrophic cardiomyopathy (HCM). However, the contribution from a wide spectrum of genetic mutations has not been well defined. We sought to investigate effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in HCM. METHODS: In 133 HCM patients, comprehensive genetic analysis was performed in 82 nuclear DNA (33 sarcomere-associated genes, 5 phenocopy genes, and 44 nuclear genes linked to mitochondrial cardiomyopathy) and 37 mitochondrial DNA. In all patients, cardiovascular magnetic resonance (CMR) was performed, including 16-segmental thickness, late gadolinium enhancement (LGE), native and post-T1, extracellular volume fraction (ECV), and T2, along with echo-Doppler evaluations. RESULTS: Patients with sarcomere mutation (SM, n = 41) had higher LGE involved segment, % LGE mass, ECV and lower post-T1 compared to patients without SM (n = 92, all p < 0.05). When classified into, non-mutation (n = 67), only mitochondria-related mutation (MM, n = 24), only-SM (n = 36) and both SM and MM (n = 5) groups, only-SM group had higher ECV and LGE than the non-mutation group (all p < 0.05). In non-LGE-involved segments, ECV was significantly higher in patients with SM. Within non-SM group, patients with any sarcomere variants of uncertain significance had higher echocardiographic Doppler E/e' (p < 0.05) and tendency of higher LGE amount and ECV (p > 0.05). However, MM group did not have significantly higher ECV or LGE amount than non-mutation group. CONCLUSIONS: SMs are significantly related to increase in myocardial fibrosis. Although, some HCM patients had pathogenic MMs, it was not associated with an increase in myocardial fibrosis.

Coronary calcification is associated with elevated serum lipoprotein (a) levels in asymptomatic men over the age of 45 years: A cross-sectional study of the Korean national health checkup data.

ABSTRACT: Lipoprotein a (Lp (a)) and coronary artery calcification (CAC) are markers of coronary artery and cardiovascular diseases. However, the association between Lp (a) and CAC in asymptomatic individuals remains unclear. In this study, we aimed to determine the influence of Lp (a) on CAC in asymptomatic individuals.We included 2019 asymptomatic Korean adults who underwent testing for a coronary artery calcium score (CACS) and Lp (a) at the Gangnam Severance Hospital Health Checkup Center in Korea from January 2017 to August 2019. Participants were divided into 2 groups: CACS = 0 and CACS > 0. Factors affecting the CACS were analyzed by sex. Because age is a major risk factor for atherosclerosis, ≥45 years in men and ≥55 years in women, we further divided participants into 4 subgroups (≥45 and <45 in men, ≥55 and <55 in women). Factors affecting the CACS in the 4 groups were analyzed.There was a positive correlation between the CACS and traditional cardiovascular risk factors. Lp (a) positively correlated with the CACS in men (P < .01) and remained significant after multivariable logistic regression (P < .01). The same result was observed in men aged ≥45 years (P < .01).Lp (a) is an independently associated factor of CAC and a marker of coronary atherosclerosis in asymptomatic men aged ≥45 years. In asymptomatic men aged ≥45 years, Lp (a) should be measured, and intensive Lp (a)-lowering treatment should be considered.

Effect of Renal and Left Ventricular Function on Serial Pulmonary Arterial Pressure Changes after Device Closure of Atrial Septal Defect.

BACKGROUND: The age of candidates for device closure of atrial septal defect (ASD) has been increasing. Thus, concerns exist about dyspnea aggravation or atrial fibrillation development after device closure due to augmentation of left ventricular (LV) and left atrial (LA) preload. This study aimed to examine patterns and determinants of serial pulmonary arterial pressure and left ventricular filling pressure changes after device closure of ASD. METHODS: Among the 86 consecutive patients who underwent percutaneous device closure of ASD, those with end-stage renal disease or those without pre- or postprocedural Doppler data were excluded. The clinical, transesophageal, and transthoracic echocardiographic findings of 78 patients were collected at baseline, one-day postprocedure, and one-year follow-up. RESULTS: The mean age of study patients was 49.8 ± 15.0 years, and the average maximal defect diameter and device size were 20.2 ± 6.0 mm and 23.8 ± 6.4 mm. Four patients (5.6%) underwent new-onset atrial fibrillation, and five patients (6.4%) took diuretics within one-year after closure. Some patients (n = 21; 27%) exhibited paradoxically increased tricuspid regurgitant velocity (TRV) one-day postprocedure; they also were older with lower e', glomerular filtration rate, and LV ejection fraction and a higher LA volume index. However, even in these patients, TRV deceased below baseline levels one-year later. Both E/e' and LA volume index significantly increased immediately after device closure, but all decreased one-year later. Larger defect size and higher TRV were significantly correlated with immediate E/e' elevation. CONCLUSION: In older, renal, diastolic, and systolic dysfunctional patients with larger LA and scheduled for larger device implantation, peri-interventional preload reduction therapy would be beneficial.

Contribution of sarcomere gene mutations to left atrial function in patients with hypertrophic cardiomyopathy.

BACKGROUND: Left atrial (LA) enlargement and dysfunction are related to clinical course in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate genetic contribution to LA structural and functional remodeling. METHODS: Two hundred twelve patients were consecutively enrolled, and echocardiography and extensive genetic analysis were performed. Cardiac magnetic resonance (CMR) was performed in 135 patients. Echocardiography was also performed in controls (n = 30). RESULTS: Patients with HCM had lower late-diastolic mitral annular velocity (a') and higher LA volume index (LAVI) than controls. Patients with pathogenic or likely pathogenic sarcomere gene mutations (PSM, n = 67, 32%) had higher LAVI and lower CMR-derived LA total emptying fraction (37.0 ± 18.5 vs. 44.2 ± 12.4%, p = 0.025). In patients without AF (n = 187), the PSM had lower a' (6.9 ± 2.0 vs. 7.8 ± 1.9 cm/s, p = 0.004) than others. The PSM had higher prevalence and amount of late gadolinium enhancement (LGE) in the left ventricle (LV). In multivariate analysis, PSM was significantly related to lower a' independent of E/e', LV mass index, and LAVI. However, the relation significantly attenuated after adjustment for the extent of LGE in the LV, suggesting common myopathy in the LV and LA. In addition, PSM was significantly related to lower LA total emptying fraction independent of age, E/e', s', LV ejection fraction, LV myocardial global longitudinal strain and %LGE mass. CONCLUSIONS: PSM was related to LA dysfunction independent of LV filling pressure and LAVI, suggesting its contribution to atrial myopathy in HCM.

Outcomes and Associated Factors of Discrepant Coronary and Carotid Atherosclerosis.

Some patients exhibit discrepancies in carotid and coronary artery atherosclerosis. This study aimed to define the characteristics and prognosis of these discrepant patients and determine the best strategy to detect pan-vascular atherosclerosis. A database of 5,022 consecutively registered patients who underwent both coronary angiography and carotid ultrasonography, along with clinical and blood laboratory tests, echocardiography, and pulse wave velocity (PWV), was analyzed. The development of cerebro-cardiovascular (CV) events during the follow-up period was also evaluated. A significant proportion of patients (n = 1,741, 35%) presented with a discrepancy between carotid artery plaque and coronary artery disease (CAD). In patients without carotid plaque, male sex (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.20-2.41; P = 0.003), older age (OR, 1.03; 95% CI, 1.01-1.04; P = 0.002), smoking history (OR, 1.58; 95% CI, 1.13-2.20; P = 0.008), lower high-density lipoprotein (HDL) -cholesterol level (OR, 0.97; 95% CI, 0.96-0.98; P < 0.001), and lower common carotid artery end-diastolic velocity (CCA-EDV) (OR, 0.97; 95% CI, 0.95-0.99; P = 0.005) were independently related to the presence of CAD. In patients without CAD, increased PWV was independently related to the presence of carotid plaque. In survival analysis, patients with isolated CAD had a higher probability of composite CV events; those with isolated carotid plaque had a higher probability of heart failure (HF) and mortality than their counterpart groups (P < 0.05). Even in patients without carotid artery plaque, careful coronary evaluation is needed in older or male patients with smoking history, lower HDL-cholesterol level, or lower CCA-EDV. Carotid plaque may be a potential risk factor for HF.

Frequent Premature Atrial Contractions as a Poor Prognostic Factor in Cryptogenic Stroke Patients with Concomitant Non-Sustained Atrial Tachycardia.

In cryptogenic stroke patients, early detection of new-onset atrial fibrillation (AF) and recurrent stroke is required to prevent poor clinical outcomes. Therefore, we investigated the predictors of new-onset AF and recurrent stroke in cryptogenic stroke patients without previously diagnosed AF. In total, 390 patients who were diagnosed with stroke and non-sustained atrial tachycardia (NSAT) on 24-hour Holter monitoring were followed up to assess new-onset AF and recurrent stroke. The 5-year event-free survival as well as the predictors of recurrent stroke or new-onset AF were investigated. Based on receiver operating characteristic analysis, frequent premature atrial contractions (PACs) were defined as PACs >44 beats/day. The median follow-up period was 35 months. The composite event rate was 11.5%. In Kaplan-Meier analysis, the 5-year cumulative incidence of composite events was higher in cryptogenic stroke patients with frequent PACs than in those without frequent PACs. Multivariate analysis revealed that current smoking, increased left atrial volume index, and frequent PACs were poor prognostic predictors of composite event, and frequent PACs were an independent poor prognostic factor of new-onset AF in cryptogenic stroke patients. Therefore, frequent PACs might be associated with poor clinical outcomes (new-onset AF and recurrent stroke) in cryptogenic stroke patients with concomitant NSAT.

Burden of premature ventricular contractions beyond nonsustained ventricular tachycardia is related to the myocardial extracellular space expansion in patients with hypertrophic-cardiomyopathy.

BACKGROUND: Although nonsustained ventricular tachycardia (NSVT) is a risk factor for sudden cardiac death in hypertrophic-cardiomyopathy (HCM), the impact of premature ventricular contraction (PVC) burden, in the absence of NSVT, is not well-known. HYPOTHESIS: PVC burden may be associated with myocardial fibrosis and genetic mutations in patients with HCM. METHODS: Of the 212 patients prospectively enrolled to the HCM registry of genetics, 84 were evaluated with both cardiac magnetic resonance, 24-hour Holter monitoring and genetic analysis. Among them, 71 patients have not been diagnosed with NSVT. RESULTS: Patients with NSVT (n = 13) had a higher late gadolinium enhancement (LGE) amount, extracellular volume fraction (ECV), and prevalence of sarcomere mutations compared with patients without NSVT. Among patients without NSVT, those with LGE (n = 46) had a higher total PVC (109 ± 332 vs 7 ± 13, P = .003) and PVC burden (0.114 ± 0.225 vs 0.008 ± 0.014%, P = .003) during 24-hour Holter monitoring compared with others. The %LGE and global ECV were correlated with PVC burden (r = 0.377, P = .001; r = 0.401, P = .001). The optimal cutoff value for PVC number for LGE was 45 (37.0% and 100% sensitivity and specificity, respectively) with 0.733 of the area under the receiver operating characteristic-curve (P < .001). Thick filament gene mutation was more prevalent in the higher PVC burden group (41.2% vs 16.7%, P = .048). CONCLUSION: Total PVC burden is significantly related to increase in myocardial fibrosis in HCM patients without NSVT.

Relationship between arterial stiffness and variability of home blood pressure monitoring.

Variability of blood pressure (BP) is known as a prognostic value for the subsequent target organ damage in hypertensive patients. Arterial stiffness is a risk factor for cardiovascular morbidity and mortality. The relationship between the arterial stiffness and the BP variability has been controversial. The objective of the present study was to investigate the relationship between arterial stiffness and home BP variability in patients with high normal BP and new onset hypertension (HTN).Four hundred sixty three patients (252 males, 49 ±â€Š12 year-old) with high normal BP or HTN were enrolled. Using radial applanation tonometry, pulse wave analysis (PWA) was performed for evaluation of systemic arterial stiffness. All patients underwent both home BP monitoring (HBPM) and PWA. Home BP variability was calculated as the standard deviation (SD) of 7 measurements of HBPM. Multiple linear regression analysis was performed to estimate and test the independent effects of home BP variability on the arterial stiffness.Mutivariate analysis showed that both systolic and diastolic morning BP variabilities were correlated with arterial stiffness expressed as augmentation pressure (AP, ß-coefficient = 1.622, P = .01 and ß-coefficient = 1.07, P = .035). The SDs of systolic and diastolic BP of evening were also associated with AP (ß-coefficient = 1.843, P = .001 and ß-coefficient = 1.088, P = .036). The SDs of morning and evening systolic BP were associated with augmentation index (AI, ß-coefficient = 1.583, P = .02 and ß-coefficient = 1.792, P = .001) and heart rate (75 bpm) adjusted AI (ß-coefficient = 1.592, P = .001 and ß-coefficient = 1.792, P = .001).In present study, the variability of systolic BP was closely related with arterial stiffness. The home BP variability might be important indicator of arterial stiffness.

Differential contributions of sarcomere and mitochondria-related multigene variants to the endophenotype of hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a multigenic disease that occurs due to various genetic modifiers. We investigated phenotype-based clinical and genetic characteristics of HCM patients using comprehensive genetic tests and rare variant association analysis. METHODS: A comprehensive HCM-specific panel, consisting of 82 nuclear DNAs (nDNAs: 33 sarcomere-associated genes, 5 phenocopy genes, and 44 nuclear genes linked to mitochondrial cardiomyopathy) and 37 mitochondrial DNAs (mtDNAs), was analyzed. Rare variant analysis was performed to determine the association of specific genes with different phenotypes. RESULTS: Among the 212 patients, pathogenic variants in sarcomere-associated genes were more prevalent in non-apical HCM (41.4%, 46/111; P = 0.001) than apical HCM (20.8%, 21/101). Apical HCM exhibits mild phenotypes than non-apical HCM, and it showed fewer numbers of sarcomere mutations than non-apical HCM. Interestingly, inverted mutation frequency of TNNI3 (35%) and MYH7 (9%) was observed in apical HCM. In a rare variant analysis, MT-RNR2 positively correlated with apical HCM (OR: 1.37, P = 0.025). And, MYBPC3 (sarcomere gene) negatively contributed to apical HCM (OR: 0.54, P = 0.027). On the other hand, both pathogenic mutation (P < 0.05) and rare variants in sarcomere-associated genes (OR: 2.78-3.47, P < 0.05) were related to diastolic dysfunction and left atrium remodeling, which correlated with poor prognosis in HCM patients. CONCLUSIONS: Our results provide a clue towards explaining the difference between the prevalence and phenotype of apical HCM in Asian populations, and a foundation for genetics-based approaches that may enable individualized risk stratification for HCM patients.

Prevalence and risk factors for secondary hypertension among young Korean men.

Screening for secondary hypertension (HTN) is recommended for early-onset HTN. However, there have been few studies on secondary HTN in young adults. We aimed to investigate the prevalence and risk factors for secondary HTN in young male military personnel. In this retrospective cross-sectional study, hypertensive men (age, 19-29 years) were identified using the electronic medical records (EMR) database between 2011 and 2017. Among them, patients with secondary HTN were confirmed through a review of the EMR. Using clinical characteristics and laboratory findings, independent predictors associated with secondary HTN were identified by binary logistic regression analysis. Secondary HTN was confirmed in 140 of 6373 participants (2.2%). Overall, the most common causes were polycystic kidney disease (n = 47, 0.74%) and renal parenchymal diseases (n = 24, 0.38%). The independent predictors of secondary HTN were abnormal thyroid function test (TFT) (odds ratio [OR]: 9.50, 95% confidence interval [CI]: 4.84-19.45, P < 0.001), proteinuria (≥ trace) (OR: 6.13, 95% CI: 2.97-12.99, P < 0.001), hematuria (≥ trace) (OR: 4.37, 95% CI: 2.15-9.01, P < 0.001), severe HTN (≥ 180/110 mmHg) (OR: 3.07, 95% CI: 1.42-6.65, P = 0.004), and non-overweight (OR: 3.03, 95% CI: 1.69-5.26, P < 0.001). However, there were no significant differences in the family history of HTN, headache, total cholesterol, and diabetes between patients with primary and secondary HTN. Therefore, to ensure cost-effectiveness, screening for secondary HTN in young hypertensive men should be performed selectively considering abnormal TFT, proteinuria, hematuria, severe HTN, and non-overweight.

Genetic relevance and determinants of mitral leaflet size in hypertrophic cardiomyopathy.

BACKGROUND: Whether mitral leaflet elongation is a primary phenotype of hypertrophic cardiomyopathy (HCM) is controversial. We investigated the genetic relevance and determinants of mitral leaflet size by performing extensive gene analyses in patients with HCM. METHODS: Anterior mitral leaflet (AML) lengths were measured in HCM patients (n = 211) and age- and sex-matched controls (n = 30) using echocardiography with hemodynamic and chamber geometric assessments. We analyzed 82 nuclear DNA (8 sarcomeric genes, 74 other HCM-associated genes) and mitochondrial DNA. Cardiac magnetic resonance imaging (CMR) was performed in the 132 HCM patients. RESULTS: Average indexed AML was significantly longer for HCM than for controls (17.2 ± 2.3 vs. 13.3 ± 1.6 mm/m2, P <  0.001). Average AML length correlated with body surface area (BSA), left ventricular (LV) end-systolic volume (P <  0.001) and LV mass by CMR (P < 0.001). Average indexed AML by BSA of pure-apical HCM was significantly shorter than other typed HCM (16.6 ± 2.0 vs. 17.4 ± 2.4 mm/m2, P = 0.025). Indexed AML was independently correlated with left atrial wall stress. The thin filament mutation group showed larger average AML (31.9 ± 3.8 vs. 29.6 ± 3.8 mm, P = 0.045), but this was not significant with the indexed value. No difference in AML size among subgroups was observed based on the presence of sarcomere protein or mitochondria-related gene variants (P > 0.05). CONCLUSION: AML elongation was a unique finding of HCM. However, the leaflet size was more related to chamber geometry and hypertrophy pattern rather than genetic factors within overt HCM.

Relationship between arterial stiffness and circadian pattern of blood pressure.

Arterial stiffness is a risk factor for cardiovascular morbidity and mortality. The relationship between the arterial stiffness and the circadian pattern of blood pressure (BP) has been controversial. The objective of the present study was to investigate the relationship between arterial stiffness by pulse wave analysis (PWA) and variables of 24-hour ambulatory BP monitoring (ABPM) in patients with high normal BP or hypertension (HTN).Five hundred forty-eight patients (304 males, 48 ±â€Š12-year-old) with high normal BP or HTN were enrolled. BP was measured at the outpatient clinic and 24-hour ABPM was performed. Using radial applanation tonometry, PWA was performed for evaluation of systemic arterial stiffness. Patients were classified into four groups according to the dipping patterns: a nocturnal dipping group, an isolated systolic non-dipping group, an isolated diastolic non-dipping group and a both systolic and diastolic non-dipping group. For adjustment of age, population was divided to 2 groups: old group ≥55 year-old (n = 158, 75 males), young group <55 year-old (n = 390, 229 males).According to the dipping patterns, augmentation pressure (AP), augmentation index (AI) and heart rate (75 bpm) adjusted AI (AI@HR75) showed statistically significant difference (P = .011, .009, and .018, respectively). Multivariate analysis showed that isolated diastolic non-dipping was correlated with arterial stiffness expressed as AI and AI@HR 75, only in young group (ß-coefficient = 12.6, P = .04 and ß-coefficient = 7.503, P = .028, respectively).Arterial stiffness might be closely related with the pattern of non-dipping in young patients with HTN and high normal BP.