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Background: Calcification of the aortic valve leads to increased leaflet stiffness and consequently to the development of calcific aortic valve disease. However, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified that dipeptidyl peptidase-4 (DPP-4, also known as CD26) increases valvular calcification and promotes calcific aortic valve disease progression.Methods: We obtained the aortic valve tissues from humans and murine models (wild-type and endothelial nitric oxide synthase-deficient-mice) and cultured the valvular interstitial cells (VICs) and valvular endothelial cells from the cusps. We induced osteogenic differentiation in the primary cultured VICs and examined the effects of the DPP-4 inhibitor on the osteogenic changes in vitro and aortic valve calcification in endothelial nitric oxide synthase-deficient-mice. We also induced calcific aortic stenosis in male New Zealand rabbits (weight, 2.5-3.0 kg) by a cholesterol-enriched diet+vitamin D2 (25 000 IU, daily). Echocardiography was performed to assess the aortic valve area and the maximal and mean transaortic pressure gradients at baseline and 3-week intervals thereafter. After 12 weeks, we harvested the heart and evaluated the aortic valve tissue using immunohistochemistry.Results: We found that nitric oxide depletion in human valvular endothelial cells activates NF-κB in human VICs. Consequently, the NF-κB promotes DPP-4 expression, which then induces the osteogenic differentiation of VICs by limiting autocrine insulin-like growth factor-1 signaling. The inhibition of DPP-4 enzymatic activity blocked the osteogenic changes in VICs in vitro and reduced the aortic valve calcification in vivo in a mouse model. Sitagliptin administration in a rabbit calcific aortic valve disease model led to significant improvements in the rate of change in aortic valve area, transaortic peak velocity, and maximal and mean pressure gradients over 12 weeks. Immunohistochemistry staining confirmed the therapeutic effect of Sitagliptin in terms of reducing the calcium deposits in the rabbit aortic valve cusps. In rabbits receiving Sitagliptin, the plasma insulin-like growth factor-1 levels were significantly increased, in line with DPP-4 inhibition.Conclusions: DPP-4-dependent insulin-like growth factor-1 inhibition in VICs contributes to aortic valve calcification, suggesting that DPP-4 could serve as a potential therapeutic target to inhibit calcific aortic valve disease progression. [ABSTRACT FROM AUTHOR]

Intermediate coronary artery stenosis (≥50% and <90%) on coronary computed tomography angiography (CTA) is usually considered as a significant lesion. However, anatomical diagnosis is not well correlated with the functional significance of myocardial ischemia. We investigated whether functional testing in addition to coronary CTA improves outcomes of patients with intermediate stenosis, compared with the 1-step CTA-aloneebased strategy. From 2006 to 2011, we consecutively enrolled 335 patients with chest pain with intermediate stenosis detected by an initially performed coronary CTA. Of these, 159 patients followed the 1-step strategy, whereas 176 followed the 2-step strategy with confirmatory functional tests. One-year follow-up data were obtained for all patients. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, and repeated or delayed revascularization (major adverse cardiac event) within a year. Baseline clinical parameters were comparable between patients of the 2 different strategies. The rate of invasive catheterization or percutaneous intervention was 75.5% in the 1-step group and 35.2% in the 2-step group (p <0.001). Consequently, more patients in the 2-step group were medically treated without unnecessary revascularization compared with patients in the 1-step group (71.0% vs 40.9%, p <0.001). Only 2.5% of the patients who received medical treatment in the 2-step group finally received delayed revascularization, whereas 14% in the 1-step group did. Overall, the primary end point occurred in 11.3% in the 1-step group and 4.0% in the 2-step group (p = 0.011). In conclusion, confirmatory functional testing reduces invasive catheterization and coronary intervention and improves clinical outcomes in patients with intermediate stenosis on coronary CTA. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 31-year-old man who was presented with paroxysmal nocturnal dyspnoea and atypical carcinoid disease primarily involving lung and pleura. Topics discussed include diagnosis of diffuse myocardial metastases of carcinoid tumour in both ventricles, use of echocardiography for the detection of myocardial thickening and use of cardiac magnetic resonance for the diagnosis of diffuse gadoliniumenhanced spotty lesions in ventricles.

BACKGROUND: Valvular heart disease (VHD) is a common cause of cardiovascular morbidity and mortality worldwide; however, its epidemiological profile in Korea requires elucidation. METHODS: In this nationwide retrospective cohort study from the Korean valve survey, which collected clinical and echocardiographic data on VHD from 45 medical centers, we identified 4,089 patients with VHD between September and October 2019. RESULTS: The aortic valve was the most commonly affected valve (n = 1,956 [47.8%]), followed by the mitral valve (n = 1,598 [39.1%]) and tricuspid valve (n = 1,172 [28.6%]). There were 1,188 cases of aortic stenosis (AS) and 926 cases of aortic regurgitation. The most common etiology of AS was degenerative disease (78.9%). The proportion of AS increased with age and accounted for the largest proportion of VHD in patients aged 80-89 years. There were 1,384 cases of mitral regurgitation (MR) and 244 cases of mitral stenosis (MS). The most common etiologies for primary and secondary MR were degenerative disease (44.3%) and non-ischemic heart disease (63.0%), respectively, whereas rheumatic disease (74.6%) was the predominant cause of MS. There were 1,172 tricuspid regurgitation (TR) cases, of which 46.9% were isolated and 53.1% were associated with other valvular diseases, most commonly with MR. The most common type of TR was secondary (90.2%), while primary accounted for 6.1%. CONCLUSIONS: This report demonstrates the current epidemiological status of VHD in Korea. The results of this study can be used as fundamental data for developing Korean guidelines for VHD. [ABSTRACT FROM AUTHOR]

BACKGROUND: It has been unclear whether statin therapy directly improves coronary flow reserve (CFR) in hypertensive patients at cardiovascular risk, independent of lifestyle modification and antihypertensive medications. METHODS: In this double-blind, randomized controlled trial, we randomly assigned 95 hypertensive patients at cardiovascular risk to receive either rosuvastatin 10 mg or placebo for 12 months, in addition to antihypertensive therapy and lifestyle modification for hypercholesterolemia. Using Doppler echocardiography, coronary flow velocity in the distal left anterior descending artery was measured and CFR was calculated as the ratio of hyperemic to basal averaged peak diastolic flow velocity. The primary end point was change in CFR from baseline to 12 months follow-up. RESULTS: Low-density lipoprotein-cholesterol was changed from 157 ± 23 to 84 ± 16 mg/dL in the rosuvastatin group (p < 0.001) and from 152 ± 19 to 144 ± 22 mg/dL in the control group (p = 0.041, but there were no significant differences between the treatment groups in the changes in C-reactive protein, high-density lipoprotein cholesterol, and blood pressures. CFR was changed from 3.03 ± 0.44 to 3.25 ± 0.49 in the rosuvastatin group (p < 0.001) and from 3.15 ± 0.54 to 3.17 ± 0.56 in the control group (p = 0.65). The primary end point of change in CFR was significantly different between the rosuvastatin group and the control group (0.216 ± 0.279 vs. 0.015 ± 0.217; p < 0.001). CONCLUSIONS: Compared with lifestyle modification alone, addition of rosuvastatin significantly improved CFR in hypertensive patients at cardiovascular risk. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hypertensive patients are at increased risk of diastolic dysfunction. The hypothesis of this study was that addition of amlodipine would be superior to valsartan in improving diastolic dysfunction associated with hypertension. METHODS: In this randomized trial, we randomly assigned 104 controlled, hypertensive patients with diastolic dysfunction to receive either amlodipine 2.5 mg or valsartan 40 mg, in addition to antihypertensive therapy. The primary end point was the change in the ratio of early mitral inflow velocity to early mitral annular relaxation velocity (E/E') from baseline to the 6-month follow-up. Secondary end points included changes in systolic blood pressure (SBP), left ventricular (LV) mass index, and left atrial volume index. RESULTS: SBP decreased significantly from baseline in both treatment groups (p < 0.001). E/E' decreased significantly from 13.0 ± 2.2 to 12.0 ± 2.7 in the amlodipine arm and from 14.4 ± 4.3 to 12.7 ± 3.7 in the valsartan arm (p < 0.01 in both groups). The change of E/E' was not significantly different between treatment groups (p = 0.25). There were also no significant between-group differences regarding the changes in SBP, LV mass index, and left atrial volume index. Two patients (3.8%) in the amlodipine group and 1 (16%) in the valsartan group had serious adverse event. CONCLUSIONS: In this randomized trial involving controlled hypertensive patients, addition of amlodipine or valsartan was associated with an improvement of diastolic dysfunction, but the effects on diastolic dysfunction did not differ significantly between the treatment groups. [ABSTRACT FROM AUTHOR]

Background: The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial.Methods: In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cm2 with either an aortic jet velocity of ≥4.5 m per second or a mean transaortic gradient of ≥50 mm Hg) to early surgery or to conservative care according to the recommendations of current guidelines. The primary end point was a composite of death during or within 30 days after surgery (often called operative mortality) or death from cardiovascular causes during the entire follow-up period. The major secondary end point was death from any cause during follow-up.Results: In the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P = 0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years.Conclusions: Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care. (Funded by the Korean Institute of Medicine; RECOVERY ClinicalTrials.gov number, NCT01161732.). [ABSTRACT FROM AUTHOR]

We present data showing that Iodotyrosine Deiodinase (IYD) is a dual-function enzyme acting as a catalyst in metabolism and a receptor for cooperative stem cell differentiation. IYD is present both in thyroid cells where it is critical for scavenging iodine from halogenated by-products of thyroid hormone production and on hematopoietic stem cells. To close the cooperative loop, the mono- and di-Iodotyrosine (MIT and DIT) substrates of IYD in the thyroid are also agonists for IYD now acting as a receptor on bone marrow stem cells. While studying intracellular combinatorial antibody libraries, we discovered an agonist antibody, H3 Ab, of which the target is the enzyme IYD. When agonized by H3 Ab, IYD expressed on stem cells induces differentiation of the cells into brown adipocyte-like cells, which selectively migrate to mouse heart tissue. H3 Ab also binds to IYD expressed on human myocardium. Thus, one has a single enzyme acting in different ways on different cells for the cooperative purpose of enhancing thermogenesis or of regenerating damaged heart tissue. [ABSTRACT FROM AUTHOR]

BACKGROUND: Overestimation of the severity of mitral regurgitation (MR) by the proximal isovelocity surface area (PISA) method has been reported. We sought to test whether angle correction (AC) of the constrained flow field is helpful to eliminate overestimation in patients with eccentric MR. METHODS: In a total of 33 patients with MR due to prolapse or flail mitral valve, both echocardiography and cardiac magnetic resonance image (CMR) were performed to calculate regurgitant volume (RV). In addition to RV by conventional PISA (RVPISA), convergence angle (α) was measured from 2-dimensional Doppler color flow maps and RV was corrected by multiplying by α/180 (RVAC). RV measured by CMR (RVCMR) was used as a gold standard, which was calculated by the difference between total stroke volume measured by planimetry of the short axis slices and aortic stroke volume by phase-contrast image. RESULTS: The correlation between RVCMR and RV by echocardiography was modest [RVCMR vs. RVPISA (r = 0.712, p < 0.001) and RVCMR vs. RVAC (r = 0.766, p < 0.001)]. However, RVPISA showed significant overestimation (RVPISA - RVCMR = 50.6 ± 40.6 mL vs. RVAC - RVCMR = 7.7 ± 23.4 mL, p < 0.001). The overall accuracy of RVPISA for diagnosis of severe MR, defined as RV ≥ 60 mL, was 57.6% (19/33), whereas it increased to 84.8% (28/33) by using RVAC (p = 0.028). CONCLUSION: Conventional PISA method tends to provide falsely large RV in patients with eccentric MR and a simple geometric AC of the proximal constraint flow largely eliminates overestimation. [ABSTRACT FROM AUTHOR]