Non-invasive one-point carotid wave intensity in a large group of healthy subjects

The analysis of wave intensity (WI) evaluates the working condition of the heart interacting with the arterial system. WI in normal subjects has two peaks, the first (W ₁) reflects left ventricle (LV) contractile performance, the second (W ₂) is related to the ability of the LV to actively stop aortic blood flow. The aim of the study was to investigate the reference values of W ₁ and W ₂ in a group of apparently healthy subjects through a radiofrequency-based system. 680 subjects (388 men mean age 43.0 ± 17.4 years, range 16–92; 292 women mean age 44.8 ± 17.7 years, range 16–86) were enrolled and underwent physical examination, blood pressure (BP) and heart rate (HR) measurements and comprehensive transthoracic echocardiogram was performed. Measurement of local WI was obtained at the level of the left common carotid artery before the bifurcation, using a high definition echo-tracking system. W ₁ was (12.37 ± 6.89) × 10³ and (9.76 ± 4.8) × 10³ mmHg m/s³, p < 0.0001; W ₂ was (3.21 ± 1.81) × 10³ and (2.98 ± 1.69) × 10³ mmHg m/s³, p = ns in men and women, respectively. The cohort was divided into 5 age groups (ages 16–29; 30–39; 40–49; 50–59; >60) and stratified by gender. After adjustment for height, systolic BP and HR, W ₁ decreased with age (p < 0.0001 in men and p = 0.026 in women for trend) while no relation was found for W ₂. Multivariable regression analysis using age, gender, height, systolic BP, HR, ejection fraction and stroke volume indexed by body surface are predicted W ₁ and age, systolic BP, HR and E/A as a measure of diastolic function, predicted W ₂. Inter and intra-observer variability and feasibility of WI analysis were satisfactory. We reported the values and their clinical correlations of the two peaks (W ₁ and W ₂) of WI, a non-invasive hemodynamic index for assessing ventricular–arterial coupling in a large group of apparently healthy subjects.     

Hemodynamic characterization of hypertensive patients with an exaggerated orthostatic blood pressure variation

Exaggerated orthostatic blood pressure variation (EOV) is a poorly understood phenomenon related to high cardiovascular risk. We aimed to determine whether hypertensive patients with EOV have a distinct hemodynamic pattern, assessed through impedance cardiography. Methods: In treated hypertensive patients, we measured the cardiac index (CI), systemic vascular resistance index (SVRI), blood pressure (BP), and heart rate (HR) in the supine and standing (after 3 minutes) positions, defining three groups according to BP variation: 1) Normal orthostatic BP variation (NOV): standing systolic BP (stSBP)-supine systolic BP (suSBP) between ?20 and 20 mmHg and standing diastolic BP (stDBP)-supine diastolic BP (suDBP) between ?10 and 10 mmHg; 2) orthostatic hypotension (OHypo): stSBP-suSBP≤-20 or stDBP-suDBP≤-10 mmHg; 3) orthostatic hypertension (OHyper): stSBP-suSBP≥20 or stDBP-suDBP≥10 mmHg. We performed multivariable analyses to determine the association of hemodynamic variables with EOV. Results: We included 186 patients. Those with OHyper had lower suDBP and higher orthostatic SVRI variation compared to NOV. In multivariable analyses, orthostatic HR variation (OR = 1.06 (95%CI 1.01–1.13), p = 0.03) and orthostatic SVRI variation (OR = 1.16 (95%CI 1.06–1.28), p = 0.002) were independently related to OHyper. No variables were independently associated with OHypo. Conclusion: Patients with OHyper have a distinct hemodynamic pattern, with an exaggerated increase in SVRI and HR when standing.     

Changes in collagen metabolism account for ventricular functional recovery following beta-blocker therapy in patients with chronic heart failure

While beta blockade improves left ventricular (LV) function in patients with chronic heart failure (CHF), the mechanisms are not well known. This study aimed to examine whether changes in myocardial collagen metabolism account for LV functional recovery following beta-blocker therapy in 62 CHF patients with reduced ejection fraction (EF). LV function was echocardiographically measured at baseline and 1, 6, and 12 months after bisoprolol therapy along with serum markers of collagen metabolism including C-terminal telopeptide of collagen type I (CITP) and matrix metalloproteinase (MMP)-2. Deceleration time of mitral early velocity (DcT) increased even in the early phase, but LVEF gradually improved throughout the study period. Heart rate (HR) was reduced from the early stage, and CITP gradually decreased. LVEF and DcT increased more so in patients with the larger decreases in CITP (r = ?0.33, p < 0.05; r = ?0.28, p < 0.05, respectively), and HR (r = ?0.31, p < 0.05; r = ?0.38, p < 0.05, respectively). In addition, there were greater decreases in CITP, MMP-2 and HR from baseline to 1, 6, or 12 months in patients with above-average improvement in LVEF than in those with below-average improvement in LVEF. Similar results were obtained in terms of DcT. There was no significant correlation between the changes in HR and CITP. In conclusion, improvement in LV systolic/diastolic function was greatest in patients with the larger inhibition of collagen degradation. Changes in myocardial collagen metabolism are closely related to LV functional recovery somewhat independently from HR reduction.     

Quality of life of liver donors following donor hepatectomy

Background

Although morbidity following living liver donation is well characterized, there is sparse data regarding health-related quality of life (HRQOL) of donors.

Methods

HRQOL of 200 consecutive live liver donors from 2011–2014 performed at an Indian center were prospectively collected using the SF-36 version 2, 1 year after surgery. The effect of donor demographics, operative details, post-operative complications (Clavien-Dindo and 50-50 criteria), and recipient mortality on the quality-of-life (QOL) scoring was analyzed.

Results

Among 200 donors (female/male=141:59), 77 (38.5%) had complications (14.5%, 16.5%, 4.5%, and 3.5%, Clavien-Dindo grades I–IV, respectively). The physical composite score (PCS) of donors 1 year after surgery was less than ideal (48.75±9.5) while the mental composite score (MCS) was good (53.37±6.16). Recipient death was the only factor that showed a statistically significant correlation with both PCS (p<0.001) and MCS (p=0.05). Age above 50 years (p<0.001), increasing body mass index (BMI) (p=0.026), and hospital stay more than 14 days ( p= 0.042) negatively affected the physical scores while emergency surgery (p<0.001) resulted in lower mental scores. Gender, postoperative complications, type of graft, or fulfillment of 50-50 criteria did not influence HRQOL. On asking the hypothetical question whether the donors would be willing to donate again, 99% reiterated there will be no change in their decision.

Conclusion

Recipient death, donation in emergency setting, age above 50, higher BMI, and prolonged hospital stay are factors that lead to impaired HRQOL following live liver donation. Despite this, 99% donors did not repent the decision to donate.

     

Effects of alcohol septal ablation on left ventricular diastolic filling patterns in obstructive hypertrophic cardiomyopathy

Alcohol septal ablation (ASA) has been shown to improve left ventricular (LV) diastolic function in patients with obstructive hypertrophic cardiomyopathy (HCM). However, its beneficial effect on diastolic function assessed by cardiac magnetic resonance (CMR) has not been reported. We investigated the mid-term changes of diastolic function by CMR combined with echocardiography in HCM patients after ASA at a median of 14-month follow-up. CMR parameters of diastolic function including peak filling rate (PFR), and time to peak filling rate (TPFR) were evaluated in 43 patients (aged 48 ± 9 years). LV diastolic function improved significantly measured by echocardiography with the decrease in ratio of transmitral early LV filling velocity (E) to early diastolic mitral lateral annular velocity (E′) (14.20 ± 1.17 to 11.58 ± 1.16, p < 0.001) and E-wave deceleration time (194.04 ± 19.30 to 168.45 ± 12.58 ms, p < 0.001). PFR increased significantly with associated decrease in TPFR after ASA (both p < 0.001) at follow-up. Furthermore, patients with larger decrease in LVOT gradients had a greater improvement of LV diastolic function, as measured by the reduction of E/E′ (p < 0.001) and increase of PFR (p < 0.001). In conclusion, this study demonstrated that successful ASA results in both echocardiographic and CMR indices of diastolic function improvement after ASA at 14-month follow-up. ASA therapy can significantly reduce LVOT gradient and mitral regurgitation, both of which may contribute to the improvement of diastolic function.     

Relationship between HRV measurements and demographic and clinical variables in a population of patients with atrial fibrillation

Little is known about the role of HRV in atrial fibrillation (AF) patients. Aim of our study was to assess the relationship between HRV measurements and demographic and clinical variables in a population of 274 AF patients. We selected all consecutive patients with persistent/permanent AF among whom had performed a Holter ECG in our Department from April 2010 to April 2015. Time-domain analysis of HRV was evaluated. Demographic and clinical variables were collected for each patient. At multivariable logistic regression, a higher pNN50 was associated with ACE inhibitors/ARBs (p = 0.016) and a lower pNN50 with obesity (p = 0.037) and higher heart rate (HR) (p < 0.0005). A higher RMSSD was associated with ACE inhibitors/ARBs (p = 0.001), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower RMSSD with a higher HR (p < 0.0005). A higher SDNN_i was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower SDNN_i with dysthyroidism (p = 0.048) and higher HR (p < 0.0005). A higher SDANN was associated with non-dihydropyiridine calcium-channel-blockers (p = 0.002) and ACE inhibitors/ARBs (p = 0.002) and a lower SDANN with hypertension (p = 0.034), obesity (p = 0.011), stroke (p = 0.031), pneumonia (p = 0.005) and higher HR (p < 0.0005). A higher SDNN was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.022) and a lower SDNN with obesity (p = 0.012), pneumonia (p = 0.049) and higher HR (p < 0.0005). Our study showed that, in AF patients, there is a direct relationship between some clinical variables and HRV measurements; as for patients with sinus rhythm, even in AF patients this relationship seemed to reflect the autonomic nervous system activity.     

Effect of CPAP therapy on cardiovascular events and mortality in patients with obstructive sleep apnea: a meta-analysis

Purpose

Continuous positive airway pressure (CPAP) therapy may decrease the risk of mortality and cardiovascular events in patients with obstructive sleep apnea. However, these benefits are not completely clear.

Methods

We undertook a meta-analysis of randomized clinical trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database.

Results

Eighteen studies (4146 patients) were included. Overall, CPAP therapy did not significantly decrease the risk of cardiovascular events compared with the control group (odds ratio (OR), 0.84; 95 % confidence intervals (CI), 0.62–1.13; p = 0.25; I ² = 0 %). CPAP was associated with a nonsignificant trend of lower rate of death and stroke (for death: OR, 0.85; 95 % CI, 0.35–2.06; p = 0.72; I ² = 0.0 %; for stroke: OR, 0.56; 95 % CI, 0.18–1.73; p = 0.32; I ² = 12.0 %), a significantly lower Epworth sleepiness score (ESS) (mean difference (MD), ?1.78; 95 % CI, ?2.31 to ?1.24; p < 0.00001; I ² = 76 %), and a significantly lower 24 h systolic and diastolic blood pressure (BP) (for 24 h systolic BP: MD, ?2.03 mmHg; 95 % CI, ?3.64 to ?0.42; p = 0.01; I ² = 0 %; for diastolic BP: MD, ?1.79 mmHg; 95 % CI, ?2.89 to ?0.68; p = 0.001; I ² = 0 %). Daytime systolic BP and body mass index were comparable between the CPAP and control groups. Subgroup analysis did not show any significant difference between short- and mediate-to-long-term follow-up groups with regard to cardiovascular events, death, and stroke.

Conclusions

CPAP therapy was associated with a trend of decreased risk of cardiovascular events. Furthermore, ESS and BP were significantly lower in the CPAP group. Larger randomized studies are needed to confirm these findings.

     

The predictability of renin–angiotensin–aldosterone system factors for clinical outcome in patients with acute decompensated heart failure

Although counter-regulation between B-type natriuretic peptide (BNP) levels and renin–angiotensin–aldosterone system (RAAS) activation in heart failure (HF) has been suggested, whether the regulation is preserved in acute decompensated heart failure (ADHF) patients remains unclear. This study aimed to determine: (1) the relationship between RAAS activation and clinical outcomes in ADHF patients, and (2) the relationships between plasma BNP levels and degrees of activation in RAAS factors. This study included ADHF patients (n = 103, NYHA3-4, plasma BNP > 200 pg/ml). We studied the predictability of RAAS factors for cardiovascular events and the relationships between plasma BNP levels and the degrees of activation in RAAS factors, which were evaluated by plasma renin activity (PRA) and aldosterone concentration (PAC). PRA was a strong predictor of cardiovascular (CV) events over 1 year, even after accounting for plasma BNP levels (hazard ratio (HR): 1.04, CI [1.02–1.06], p < 0.01) and medication such as RAAS blockers (HR: 1.03, CI [1.01–1.05], p < 0.01), whereas PAC was borderline-significant (univariate analysis, p = 0.06). Cut-off value of PRA (5.3 ng/ml/h) was determined by AUC curve. Of the enrolled patients, higher PRA was found in 40 % of them. Although no correlation between the plasma BNP levels and PRA was found (p = 0.36), after adjusting for hemodynamic parameters, eGFR and medication, a correlation was found between them (p = 0.01). Elevated RAAS factors were found in a substantial number of ADHF patients with high plasma BNP levels in the association with hemodynamic state, which predicts poor clinical outcomes. The measurements of RAAS factors help to stratify ADHF patients at risk for further CV events.     

Subendocardial viability ratio in patients with rheumatoid arthritis: comparison with healthy controls and identification of prognostic factors

Cardiac involvement is common in rheumatoid arthritis. Subendocardial viability ratio (SEVR) is a non-invasive measure of microvascular coronary perfusion, yet it remains unclear whether it is affected in rheumatoid arthritis patients. We additionally sought predictors of SEVR in rheumatoid arthritis among a wide range of disease-related parameters, cardiac and hemodynamic factors, and markers of atherosclerosis, arteriosclerosis, and endothelial dysfunction. SEVR was estimated in rheumatoid arthritis patients and healthy controls by applanation tonometry, which was also used to evaluate arterial stiffness (pulse wave velocity and augmentation index). In the rheumatoid arthritis group, carotid intima–media thickness (cIMT) was additionally estimated by ultrasound, cardiac and hemodynamic parameters by impedance cardiography, and endothelial dysfunction by measurement of asymmetric dimethylarginine (ADMA). In a total of 122 participants, SEVR was lower among 91 patients with rheumatoid arthritis compared to 31 controls (141.4 ± 21.9 vs 153.1 ± 18.7%, p = 0.009) and remained so among 29 rheumatoid arthritis patients without hypertension, diabetes, or cardiovascular diseases, compared to the control group (139.7 ± 21.7 vs 153.1 ± 18.7%, p = 0.013). SEVR did not significantly correlate with arterial stiffness, cIMT, ADMA, or disease-related parameters. Multivariate analysis revealed gender (p = 0.007), blood pressure (p = 0.028), heart rate (p = 0.025), cholesterol levels (p = 0.008), cardiac index (p < 0.001) and left ventricular ejection time (p = 0.004) as independent predictors of SEVR among patients with rheumatoid arthritis. Patients with rheumatoid arthritis exhibit lower values of SEVR compared to healthy individuals. Cardiac and hemodynamic parameters, rather than functional indices of endothelial and macrovascular dysfunction, may be useful as predictors of myocardial perfusion in rheumatoid arthritis.     

Ankylosing spondylitis diagnosis in US patients with back pain: identifying providers involved and factors associated with rheumatology referral delay

This study aimed to identify providers involved in diagnosing ankylosing spondylitis (AS) following back pain diagnosis in the USA and to identify factors leading to the delay in rheumatology referrals. The Truven Health MarketScan® US Commercial Database was searched for patients aged 18–64 years with back pain diagnosis in a non-rheumatology setting followed by AS diagnosis in any setting during January 2000–December 2012. Patients with a rheumatologist visit on or before AS diagnosis were considered referred. Cox regression was used to determine factors associated with referral time after adjusting for age, sex, comorbidities, physician specialty, drug therapy, and imaging procedures. Of 3336 patients included, 1244 (37 %) were referred to and diagnosed by rheumatologists; the others were diagnosed in primary care (25.7 %), chiropractic/physical therapy (7 %), orthopedic surgery (3.8 %), pain clinic (3.6 %), acute care (3.4 %), and other (19.2 %) settings. Median time from back pain diagnosis to rheumatology referral was 307 days and from first rheumatologist visit to AS diagnosis was 28 days. Referred patients were more likely to be younger (hazard ratio [HR]?=?0.986; p?<?0.0001), male (HR?=?1.15; p?=?0.0163), diagnosed with uveitis (HR?=?1.49; p?=?0.0050), referred by primary care physicians (HR?=?1.96; p?<?0.0001), prescribed non-steroidal anti-inflammatory drugs (HR?=?1.55; p?<?0.0001), disease-modifying antirheumatic drugs (HR?=?1.33; p?<?0.0001), and tumor necrosis factor inhibitors (HR?=?1.40; p?=?0.0036), and to have had spinal/pelvic X-ray prior to referral (HR?=?1.28; p?=?0.0003). During 2000–2012, most patients with AS were diagnosed outside of rheumatology practices. The delay before referral to rheumatology was 10 months; AS diagnosis generally followed within a month. Earlier referral of patients with AS signs and symptoms may lead to more timely diagnosis and appropriate treatment.     

The Effect of a Community-Based Exercise Program on Inflammation,Metabolic Risk,and Fitness Levels Among Persons Living with HIV/AIDS

The human immunodeficiency virus (HIV) pandemic remains a top national health priority. Chronic inflammation may be a critical component in the disease course of HIV as C-reactive protein (CRP) is elevated and associated with increased mortality. This study examined the effect of 3 months of combined aerobic and resistance exercise training among a diverse cohort of HIV-infected men and women. The fixed effect of time for CRP was found to be non-significant (F[1,57.3] = 1.7, p = 0.19). There was a significant fixed effect for time for upper body (F[1,51.6] = 18.1, p < 0.05) and lower body strength (F[1,48.0] = 15.7, p < 0.05) and significant declines in diastolic blood pressure (p = 0.002) and waist circumference (p = 0.027). Though levels of CRP were not impacted after 3 months training, participants demonstrated a significant increase in muscular strength as well as beneficial changes in metabolic risk factors. Future studies should focus on determining the optimal exercise intervention length and mode to reduce inflammation among individuals living with HIV.     

Linkage of sleep-disordered breathing and acute aortic dissection with patent false lumen

Sleep-disordered breathing (SDB) is known as a cardiovascular risk factor and has high prevalence in hypertension, which is a major risk factor of aortic dissection (AD). However, the impact of SDB on AD has not been fully clarified. The aim of this study is to elucidate the impact of SDB on AD, especially on the type of false lumen in AD. We enrolled twenty-three consecutive patients with acute AD (mean age: 66 ± 13 years). All subjects were evaluated by an ambulatory polygraphic sleep monitoring within 1 month from the onset. AD was evaluated by axial images of computed tomography. We comparatively analyzed SDB and AD. 35 % of the subjects presented severe OSA (apnea–hypopnea index: AHI ≥30). The patent false lumen group showed significantly higher systolic and diastolic blood pressure (BP) on arrival and AHI, and lower percutaneous oxygen saturation (SaO₂) compared with those in the thrombosed false lumen group. The prevalence of severe SDB was higher in the patent false lumen group (60 vs 15 %, p = 0.039). Systolic BP on arrival was significantly correlated with AHI (r = 0.457, p = 0.033) and the minimum SaO₂ (r = ?0.537, p = 0.010). The present study revealed close linkage between SDB and AD, and a high prevalence of SDB among AD patients. Severe SDB was related to the development of AD, especially for the patent false lumen type through highly elevated BP which might be easily evoked in the presence of severe SDB. Repetitive occurrence of intrathoracic negative pressure also might influence the repair or closure of false lumen of AD, although the present analysis did not reach statistical significance.     

Surgical Resection for Pulmonary Carcinoid: Long-Term Results of Multicentric Study—The Importance of Pathological N Status,More Than We Thought

Background

Histological subdivision into typical (TC) and atypical (AC) is crucial for treatment and prognosis of lung carcinoids but can be also very challenging, even for experts. In this study, we aimed to strengthen or reduce the prognostic value of several pathological, clinical, or per-operative factors some of which are still controversial.

Methods

We retrospectively reviewed clinical records related to 195 patients affected by TC (159) or AC (36) surgically treated between 2000 and 2014, in three different centers. Survival and subtypes comparison analyses were performed to identify potential prognostic factors.

Results

TCs showed a lower rate of nodal involvement than ACs (N0 = 94.9%; N1 = 1.9%; N2 = 3.2% in typical and N0 = 63.8%; N1 = 16.6%; N2 = 19.4% in atypical carcinoids, respectively, p < 0.0001). Long-term oncological results of resected carcinoids were significantly better in TCs than ACs with higher 5- and 10-year overall survival rates (97.2 and 88.2% vs. 77.9 and 68.2%, respectively; p = 0.001) and disease-free survival rates (98.2 and 90.3% in typical and 80.8 and 70.7% atypical carcinoids, respectively; p = 0.001). Risk factors analysis revealed that AC subtype [HR 4.33 (95% CI 1.72–8.03), p = 0.002], pathological nodal involvement [HR 3.05 (95% CI 1.77–5.26), p < 0.0001], and higher SUV_max [HR 4.33 (95% CI 1.03–7.18), p = 0.002] were independently and pejoratively associated with overall survival. Factors associated with a higher risk of recurrence were AC subtype [HR 6.13 (95% CI 1.13–18.86), p = 0.002]; nodal involvement [HR 5.48 (95% CI 2.85–10.51), p < 0.0001]; higher Ki67 expression level [HR 1.09 (95% CI 1.01–1.20), p = 0.047]; and SUV_max [HR 1.83 (95% CI 1.04–3.23), p = 0.035].

Conclusion

Surgery for lung carcinoids allows satisfactory oncological results which mainly depend on carcinoid subtype dichotomy, pathological nodal status, and SUV_max.

     

SOFA score and left ventricular systolic function as predictors of short-term outcome in patients with sepsis

In a group of septic patients, we assess the short-term prognostic value of LV systolic performance, evaluated through conventional left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (LV GLS). One hundred forty-seven patients with sepsis were recruited; LVEF by planimetry and peak GLS by 2D speckle tracking could be assessed within 24 h. The study population was stratified according to SOFA tertiles assessed at the time of the echocardiogram (G1: SOFA score <5; G2: SOFA score 5–7; G3: SOFA score >7). Day-7 follow-up data were used as reference. Patients in G2 and G3 show a significant hemodynamic derangement, paralleling the more pronounced organ damage by definition; nevertheless, LVEF and GLS are comparable among the three groups (both p > 0.1). All-cause mortality at day-7 follow-up is slightly lower in G1 (9%) versus G2 and G3 (14 and 26%, respectively, p = NS). Analyses through ROC curves focusing on day-7 mortality show that the SOFA score fairly correlates with events (AUC 0.635, p = 0.037), while low LVEF (AUC 0.35, p = 0.022) and less negative GLS (AUC 0.73, p = 0.001) do so. In multivariate analyses, mortality by day-7 follow-up is more likely per higher GLS (i.e., indicative of worst systolic dysfunction, HR 1.22/%, p = 0.005) and per increasing SOFA score (HR 1.22/unit, p = 0.010), whereas LVEF, adjusted for age and SOFA score, does not enter the prognostic model. In the very short term in patients with severe sepsis, LV systolic function assessment by means of GLS predicts the short-term prognosis, independent of SOFA.     

Teneligliptin improves left ventricular diastolic function and endothelial function in patients with diabetes

Incretin hormones have been reported to have cytoprotective actions in addition to their glucose-lowering effects. We evaluated whether teneligliptin, a novel dipeptidyl peptidase-4 (DPP-4) inhibitor, affects left ventricular (LV) function in patients with type 2 diabetes mellitus (T2DM). Twenty-nine T2DM patients not receiving any incretin-based drugs were enrolled and prescribed with teneligliptin for 3 months. Compared to baseline levels, hemoglobin A1c levels decreased (7.6 ± 1.0 % to 6.9 ± 0.7 %, p < 0.01) and 1,5-anhydro-d-glucitol levels increased (9.6 ± 7.2 μg/mL to 13.5 ± 8.7 μg/mL, p < 0.01) after treatment. Clinical parameters, including body mass index and blood pressure, did not show any difference before and after treatment. Three months after treatment, there were improvements in LV systolic and diastolic function [LV ejection fraction, 62.0 ± 6.5 % to 64.5 ± 5.0 %, p = 0.01; peak early diastolic velocity/basal septal diastolic velocity (E/e′) ratio, 13.3 ± 4.1 to 11.9 ± 3.3, p = 0.01]. Moreover, there was an improvement in endothelial function (reactive hyperemia peripheral arterial tonometry [RH-PAT] index; 1.58 ± 0.47 to 2.01 ± 0.72, p < 0.01). There was a significant negative correlation between changes in the E/e’ ratio and RH-PAT values. Furthermore, circulating adiponectin levels increased (27.0 ± 38.5 pg/mL to 42.7 ± 33.2 pg/mL, p < 0.01) without changes in patient body weight. Teneligliptin treatment was associated with improvements in LV function and endothelial functions, and an increase in serum adiponectin levels. These results support the cardio-protective effects of teneligliptin in T2DM patients and increase in serum adiponectin levels.     

Long-term effects of L- and N-type calcium channel blocker on uric acid levels and left atrial volume in hypertensive patients

Left ventricular (LV) diastolic dysfunction is associated with hypertension and hyperuricemia. However, it is not clear whether the L- and N-type calcium channel blocker will improve LV diastolic dysfunction through the reduction of uric acid. The aim of this study was to investigate the effects of anti-hypertensive therapy, the L- and N-type calcium channel blocker, cilnidipine or the L-type calcium channel blocker, amlodipine, on left atrial reverse remodeling and uric acid in hypertensive patients. We studied 62 patients with untreated hypertension, randomly assigned to cilnidipine or amlodipine for 48 weeks. LV diastolic function was assessed with the left atrial volume index (LAVI), mitral early diastolic wave (E), tissue Doppler early diastolic velocity (E′) and the ratio (E/E′). Serum uric acid levels were measured before and after treatment. After treatment, systolic and diastolic blood pressures equally dropped in both groups. LAVI, E/E′, heart rate and uric acid levels decreased at 48 weeks in the cilnidipine group but not in the amlodipine group. The % change from baseline to 48 weeks in LAVI, E wave, E/E′ and uric acid levels were significantly lower in the cilnidipine group than in the amlodipine group. Larger %-drop in uric acid levels were associated with larger %-reduction of LAVI (p < 0.01). L- and N-type calcium channel blocker but not L-type calcium channel blocker may improve LV diastolic function in hypertensive patients, at least partially through the decrease in uric acid levels.     

Three-question set from Michigan Neuropathy Screening Instrument adds independent prognostic information on cardiovascular outcomes: analysis of ALTITUDE trial

Aims/hypothesis

The self-administered Michigan Neuropathy Screening Instrument (MNSI) is used to diagnose diabetic peripheral neuropathy. We examined whether the MNSI might also provide information on risk of death and cardiovascular outcomes.

Methods

In this post hoc analysis of the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial, we divided 8463 participants with type 2 diabetes and chronic kidney disease (CKD) and/or cardiovascular disease (CVD) into independent training (n = 3252) and validation (n = 5211) sets. In the training set, we identified specific questions that were independently associated with a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction/stroke, heart failure hospitalisation). We then evaluated the performance of these questions in the validation set.

Results

In the training set, three questions (‘Are your legs numb?’, ‘Have you ever had an open sore on your foot?’ and ‘Do your legs hurt when you walk?’) were significantly associated with the cardiovascular composite outcome. In the validation set, after multivariable adjustment for key covariates, one or more positive responses (n = 3079, 59.1%) was associated with a higher risk of the cardiovascular composite outcome (HR 1.54 [95% CI 1.28, 1.85], p < 0.001), heart failure hospitalisation (HR 1.74 [95% CI 1.29, 2.35], p < 0.001), myocardial infarction (HR 1.81 [95% CI 1.23, 2.69], p = 0.003), stroke (HR 1.75 [95% CI 1.20, 2.56], p = 0.003) and three-point major adverse cardiovascular events (MACE) (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) (HR 1.49 [95% CI 1.20, 1.85], p < 0.001) relative to no positive responses to all questions. Associations were stronger if participants answered positively to all three questions (n = 552, 11%). The addition of the total number of affirmative responses to existing models significantly improved Harrell’s C statistic for the cardiovascular composite outcome (0.70 vs 0.71, p = 0.010), continuous net reclassification improvement (+22% [+10%, +31%], p = 0.027) and integrated discrimination improvement (+0.9% [+0.4%, +2.1%], p = 0.007).

Conclusions/interpretation

We identified three questions from the MNSI that provide additional prognostic information for individuals with type 2 diabetes and CKD and/or CVD. If externally validated, these questions may be integrated into the clinical history to augment prediction of CV events in high-risk individuals with type 2 diabetes.

     

Pharmacokinetic comparison of cyclosporin A and tacrolimus in graft-versus-host disease prophylaxis

A number of studies were published with contradictory results comparing tacrolimus (Tac) and cyclosporine A (CsA) for graft-versus-host disease (GVHD) prophylaxis, but there are only few that accounted for pharmacokinetic (PK) parameters. In this study, we created a model based on median concentrations, variability of concentrations, and failures to maintain target levels that distinguished patients with low, intermediate, and high risks of acute GVHD (hazard ratios (HR) 1.77, 95%CI 1.36–2.32, p < 0.0001). This model was used to compare 95 patients with CsA and 239 with Tac GVHD prophylaxis. In the multivariate analysis, incorporating PK risk, no differences were observed for grade II–IV acute GVHD (HR 0.73, 95%CI 0.48–1.10, p = 0.13), but grade III–IV acute GVHD was lower in the Tac group (HR 0.47, 95%CI 0.28–0.78, p = 0.004). The observed difference was due to patients with high PK risk (HR 0.377, 95%CI 0.19–0.75, p = 0.005), but not with low and intermediate PK risk (p > 0.05). Patients in the Tac group had better GVHD relapse-free survival (HR = 0.659, p = 0.01) and comparable overall survival (p > 0.05). In conclusion, PK risk should be accounted for in comparisons of GVHD prophylaxis regimens with calcineurin inhibitors, and Tac was superior to CsA in patients with high, but not intermediate and low PK risk.     

Assessment of risk factors and left ventricular function in patients with slow coronary flow

Slow coronary flow (SCF) is characterized by delayed distal vessel opacification in the absence of significant epicardial coronary disease. Life-threatening arrhythmias and sudden cardiac death can occur; however, the pathological mechanism and influence on left ventricular function remain undetermined. We aimed to assess the risk factors and left ventricular (LV) function in SCF and evaluate the relationships between thrombolysis in myocardial infarction frame count (TFC) and the number of involved coronary arteries with LV function in patients with SCF. We included 124 patients who underwent coronary angiography because of symptoms of angina; 71 patients with angiographically proven SCF and 53 cases with normal coronary flow pattern. SCF was diagnosed as TFC >27 in at least one coronary artery. Complete blood count and biochemical parameters were compared between the two groups. Conventional echocardiography and tissue Doppler imaging were used to assess LV systolic and diastolic function. Platelet aggregation rate induced by ADP was an independent predictor of SCF and positively correlated with coronary artery mean TFC (mTFC) (r = 0.514, P < 0.001) and the number of coronary arteries with SCF (r = 0.628, P < 0.001). Early diastolic mitral inflow velocity (E) (0.66 ± 0.15 vs. 0.74 ± 0.17, P = 0.008), ratio of early to late diastolic mitral inflow velocity (E/A) (0.95 ± 0.29 vs. 1.15 ± 0.35, P = 0.002), global myocardial peak early diastolic velocity (gVe) (4.41 ± 1.25 vs. 4.96 ± 1.45, P = 0.037), and ratio of global myocardial peak early to late diastolic velocity (gVe/gVa: 1.09 ± 0.45 vs. 1.36 ± 0.58, P = 0.006) were decreased in patients with SCF compared with controls. gVe (3 vs. 0 branches, 4.08 ± 1.14 vs. 4.97 ± 1.45, respectively, P = 0.008) deteriorated significantly in patients with SCF involving three coronary arteries. mTFC negatively correlated with E and E/A (r = ?0.22, P = 0.02; r = ?0.20, P = 0.04, respectively). The number of coronary arteries with SCF negatively correlated with E, E/A, gVe and gVe/gVa (r = ?0.23, P = 0.02; r = ?0.25, P = 0.009; r = ?0.25, P = 0.008; r = ?0.21, P = 0.03, respectively). Platelet aggregation rate induced by ADP was an independent predictor of SCF and positively correlated with coronary artery TFC and the number of affected coronary arteries. Left ventricular global and regional diastolic function was impaired in SCF patients. Furthermore, the number of coronary arteries involved rather than coronary artery TFC determined the severity of left ventricular dysfunction in patients with SCF.