Quan Fang

The prognostic value of left ventricular systolic function measured by tissue Doppler imaging in septic shock

IntroductionLeft ventricular (LV) dysfunction is common in septic shock. Its association with the clinical outcome is still controversial. Tissue Doppler imaging (TDI) is a useful tool to quantify LV function; however, little knowledge is available about the prognostic value of these TDI variables in septic shock. Therefore, we performed this prospective study to determine the role of TDI variables in septic shock.MethodsPatients with septic shock in a medical intensive care unit were studied with transthoracic echocardiography with TDI within 24 hours after the onset of septic shock. Baseline clinical, laboratory, and echocardiographic variables were prospectively collected. Independent predictors of 90-day mortality were analyzed with the Cox regression model.ResultsDuring a 20-month period, 61 patients were enrolled in the study. The 90-day mortality rate was 39%; the mean APACHE IV score was 84 (68 to 97). Compared with survivors, nonsurvivors exhibited significantly higher peak systolic velocity measured at the mitral annulus (Sa) (11.0 (9.1 to 12.5) versus 7.8 (5.5 to 9.0) cm/sec; P < 0.0001), lower PaO2/FiO2 (123 (83 to 187) versus 186 (142 to 269) mm Hg; P = 0.002], higher heart rate (120 (90 to 140) versus 103 (90 to 114) beats/min; P = 0.004], and ahigher dose of norepinephrine (0.6 (0.2 to 1.0) versus 0.3 (0.2 to 0.5) μg/kg/min; P = 0.007]. In the multivariate analysis, Sa > 9 cm/sec (hazard ratio (HR), 5.559; 95% confidence interval (CI), 2.160 to 14.305; P < 0.0001), dose of norepinephrine (HR, 1.964; 95% CI, 1.338 to 2.883; P = 0.001), and PaO2/FiO2 (HR, 0.992; 95% CI, 0.984 to 0.999; P = 0.031) remain independent predictors of 90-day mortality in septic-shock patients.ConclusionsOur study demonstrated that LV systolic function as determined by TDI, in particular, Sa, might be associated with mortality in patients with septic shock.

HIV infection: an independent risk factor of peripheral arterial disease.

To the Editors: Highly active antiretroviral therapy (HAART) had significantly reduced the death rate resulted from HIV infection. However, HAART had also increased the risk of coronary heart disease in HIVinfected patients, especially in those on protease inhibitors (PIs). Whether HIV infection itself can promote the atherosclerosis is still controversial. Ankle brachial index (ABI) has been validated against lower extremity contrast angiography to determine its sensitivity, specificity, and accuracy as a diagnostic tool for lower extremity peripheral arterial disease, and the presence of a low ABI was predictive of total and cardiovascular mortality. Pulse wave velocity (PWV) is noninvasive parameter directly proportional to arterial wall stiffness. Our study aimed to determine whether the HIVinfected patients with or without receiving HAART are more likely to develop atherosclerosis in comparison to the general population, using ABI and PWV; and to assess the associated factors of peripheral arterial atherosclerosis. Our study had been approved by Peking Union Medical College Hospital Institutional Review Board. Eighty-two patients with HIV infection were divided into 2 groups: antiretroviral therapy (ART) na€ıve group comprising 41 antiretroviral-naive patients and HAARTtreated group comprising 41 patients on HAART for more than 12 months (34.76 17.1 months). Forty-three healthy people whose HIV screen tests were negative were enrolled as control subjects. Total cholesterol, triglyceride, lowdensity lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined by standard methods using Olympus AU5400 chemistry autoanalyzer (Olympus, Tokyo, Japan). CD4 lymphocyte count and CD8 lymphocyte count were measured by Epics XL flow cytometry (Beckman Coulter, Ramsey, MN). Plasma HIV RNA level was determined using a branched DNA assay (lower limit of quantification, 50 copies RNA/mL, version 3.0; Bayer Health Care, Leverkusen, Germany). ABI and PWV were determined using a pulse pressure analyzer (model BP-203RPE II; Nihon Colin, Komaki, Japan). The ABI was performed by measuring the systolic blood pressure from both brachial arteries and from both posterior tibial arteries; ABI was then calculated by the device as the ratio of systolic blood pressure in the leg to that in the arm on each side, and the average value was used for analysis. Pulse waves were recorded using sensors placed on both posterior tibial arteries. The time intervals required for the pulse waves to travel from the heart to both posterior tibial arteries were measured, and the distances between the heart and both posterior tibial arteries were estimated from the patient’s height. The PWV was calculated by dividing the distance by the time interval. For statistical analysis, between-group differences were compared by 2-sample t tests or Mann– Whitney tests (non-normal distribution) for continuous variables and by x analysis for categorical variables. Correlation was tested with Spearman rank order or Pearson correlation coefficient. Multiple linear regression analysis was used to test for independent associations between ABI and various factors. No significant statistical differences were observed among 3 groups considering age, sex, and family history of coronary heart disease or current smoking (Table 1). The ART-naive patients were more likely to be hypertensive and had lower level of total cholesterol and LDL-C than control subjects (P < 0.01). A lower HDL-C level was also noted in our ART-naive patients (P < 0.01). ART na€ıve HIV-infected patients have a lower ABI (P < 0.001) and a higher PWV (P = 0.010) when compared with control subjects. We included 41 ART-naive patients and 43 control subjects in a single group for linear regression analysis (R = 0.362; P = 0.001). We found that factors associated with reduced ABI were age (B = 0.03; 95% confidence interval: 0.000–0.005; P = 0.039) and HIV infection (B = 0.069; 95% confidence interval: 0.120 to 0.017; P = 0.01). That meant, after adjustment for other cardiovascular risk factors, HIV infection group was associated with a 0.069 lower ABI compared with control subjects. However, Pearson relation analysis shows not any association between ABI and common HIV infection parameters [CD4 lymphocyte count (r = 0.161; P = 0.314), CD8 lymphocyte count (r = 0.026; P = 0.871), CD4/CD8 ratio (r = 0.055; P = 0.731), and HIV RNA (r = 0.047; P = 0.770)] in patients with HIV. Patients in HAART-treated group mostly were treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs, 40 of 41, 98%) and nucleoside reverse transcriptase inhibitors (NRTIs, 41 of 41, 100%). Only 7.3% (3 of 41) of the patients were on PIs–containing regimen. There were no differences in total cholesterol, triglyceride, LDL-C, HDL-C, and ABI between HAART-treated group and ART-naive group. Compared with ART-naive patients, the HAART-treated patients showed a lower body mass index, blood pressure, and PWV, as well as the HIV RNA level (P < 0.05). The idea that HIV-infected patients are likely to have an atherogenic lipid profile, such as high levels of total cholesterol, LDL-C, and triglyceride, has been reported by several studies. HAART is thought to be associated with these metabolic abnormalities. However, our ART-naive patients had lower total cholesterol and LDL-C levels, which is an atheroprotective lipid profile. This result supports the assumption that HAART may be contributory to dyslipidemia in HIV-infected patients. In this study, we proved that ART-naive patients have lower ABI compared with HIVuninfected control subjects, suggesting that HIV-infected patients are more likely to develop peripheral arterial disease. We also found in ART-naive HIV-infected patients having higher PWV level, which is also a marker of Supported by National Key Technologies R&D Program for the 11th Five-year Plan (2008ZX10001-006), Ministry of Health Clinical HIV/AIDS Research Grant (2007–2009), and Beijing Science and Technology Program Fund (D0906003040491).

Danon disease as a cause of concentric left ventricular hypertrophy in patients who underwent endomyocardial biopsy

BACKGROUND Danon disease is an X-linked dominant disorder; concentric left ventricular hypertrophy (LVH) is one of its manifestations. In this study, we investigated the prevalence of Danon disease in patients with concentric LVH who underwent endomyocardial biopsy (EMB). METHODS AND RESULTS A total of 50 patients with concentric LVH underwent EMB from January 2008 to December 2010. Cardiac amyloidosis was diagnosed in 14 patients; genetic analysis of lysosome-associated membrane protein 2 (LAMP2) was done in the remaining 36 patients. Three novel LAMP2 frameshift mutations were found. They were c.808_809 insG in exon 6, c.320_321 insCATC in exon 3, and c.257_258delCC in exon 3, leading to a premature stop codon on cDNA analysis. The prevalence of Danon disease was seen in 6% (3 of 50) of unselected concentric LVH patients who underwent EMB, or 8% (3 of 36) after excluding cardiac amyloidosis through EMB. All the three patients were male teenagers with a mean age of 15 ± 1 years, and had mild mental retardation, two of the three with Wolff-Parkinson-White (WPW) syndrome and markedly increased left ventricular voltage. All the three patients had increased serum hepatic enzymes and creatine kinase (CK) concentrations. There was no death or cardiovascular hospitalization during 20 ± 15 months of follow-up. CONCLUSIONS Danon disease may account for a number of patients with concentric LVH who underwent EMB. Danon disease should be suspected in the male teenager with concentric LVH, especially with elevated serum hepatic enzymes and CK concentrations, and/or WPW syndrome with markedly increased voltage of the left ventricle. Genetic analysis of LAMP2 can help make the diagnosis.

Utility of Combined Indexes of Electrocardiography and Echocardiography in the Diagnosis of Biopsy Proven Primary Cardiac Amyloidosis

Objective: Primary cardiac amyloidosis (CA) is associated with poor prognosis. However, the noninvasive diagnostic tools are limited. The aim of the study is to assess the utility of combined indexes of electrocardiography (ECG) and echocardiography (ECHO) in the diagnosis of primary CA.

Effect of statins in preventing contrast-induced nephropathy: an updated meta-analysis.

ObjectiveThe effect of statins in preventing contrast-induced nephropathy (CIN) has been reported, with conflicting results. The aim of this study was to carry out an updated meta-analysis to determine whether pretreatment with statins can reduce the risk of CIN and adverse clinical events. Materials and methodsSystematic database searches of MEDLINE (1950 to December 2013), EMBASE (1966 to December 2013), and the Cochrane Central Register of Controlled Trials (Issue 12, December 2013) were performed. All randomized controlled trials assessing the efficacy of statins on CIN were included. ResultsSeventeen studies with 6323 patients were included. Pretreatment with statins before angiography significantly reduced the risk of CIN [relative risk 0.50; 95% confidence interval (CI) 0.35–0.71; P<0.001] and was associated with significantly lower postprocedural serum creatinine levels (weighted mean difference −0.05 mg/dl; 95% CI −0.09 to −0.02 mg/dl; P=0.005). Meanwhile, the use of statins resulted in trends of reduced risks of renal replacement therapy and all-cause death within 30 days (relative risk 0.44; 95% CI 0.18–1.08; P=0.07). Further analyses indicated that high-dose statins were more effective than low-dose statins in reducing the risk of CIN and that different types of statins showed similar effects in preventing CIN. ConclusionPretreatment with statins before angiography is effective in preventing CIN and may reduce the risk of adverse clinical events. However, the optimal dose and duration for statin pretreatment are still unknown.

Urokinase receptor surface expression regulates monocyte migration and is associated with accelerated atherosclerosis

BACKGROUND The urokinase receptor (uPAR) is a key regulator of pericellular proteolysis, cell adhesion and migration, all of which are fundamental processes in atherogenesis. We hypothesized that increased monocytic uPAR expression in circulation is associated with the formation and development of atherosclerosis. METHODS A total of 42 male apoE-/- mice were ramdonly divided into high-fat (HF) diet and normal diet (n=21 per group). The percentage of uPAR expressing monocytes (PUEM) and the expression of uPAR within different types of atherosclerotic plaques were measured at an interval of 3 weeks from week 10 to week 16. In vitro, uPAR expression upon ox-LDL stimulation and the migration of monocytes were examined. RESULTS PUEM in circulation was significantly higher in animals with HF diet compared with those having normal diet (p<0.03). The augmented levels of PUEM were associated with body weight, visceral fat weight and numbers of uPAR+macrophages within atherosclerotic lesions. Accumulation of uPAR+macrophages increased with the progression of atherosclerosis. Monocytes upon ox-LDL stimulation exhibited an increased uPAR expression and uPAR antibody markedly suppressed monocyte migration induced by monocyte chemotactic protein-1. uPAR modulated monocyte migration was accelerated by uPA and was suppressed by amino terminal fragment of uPA dependent. CONCLUSIONS Over-expression of uPAR both in circulating monocytes and in atherosclerotic lesions is associated with the development of atherosclerotic plaques. uPAR and its interaction with uPA may contribute to enhanced monocyte migration. Thus, uPAR may be a novel target for prevention of uncontrolled monocyte recruitment in inflammatory atherogenic process.

The R-wave deflection interval in lead V3 combining with R-wave amplitude index in lead V1: a new surface ECG algorithm for distinguishing left from right ventricular outflow tract tachycardia origin in patients with transitional lead at V3.

BACKGROUND To distinguish left ventricular outflow tract (LVOT) from right ventricular outflow tract (RVOT) origin in idiopathic premature ventricular contractions or ventricular tachycardia (PVCs/VT) patients with transitional lead at V3 is still a challenge. We sought to develop a new electrocardiography (ECG) algorithm for distinguishing LVOT from RVOT origin in patients with idiopathic outflow tract PVCs/VT with precordial transitional lead at V3. METHODS We analyzed the surface ECG characteristics in a retrospective cohort of idiopathic PVCs/VT patients with transitional lead at V3 who underwent successful radiofrequency catheter ablation and developed a new surface ECG algorithm, then validated it in a prospective cohort. RESULTS A total of 82 consecutive patients (47 ± 17 years, 39% male) underwent radiofrequency catheter ablation of idiopathic outflow tract PVCs/VT between January 2006 and August 2010. Among them, 31 patients (38%) with transitional lead at V3 constituted the retrospective cohort. Based on the areas under the receiver operating characteristic curves, R-wave deflection interval in lead V3>80 ms and R-wave amplitude index in lead V1>0.30 were selected to develop the new surface ECG algorithm. It correctly identified the origin sites of eleven from 12 patients in the prospective cohort, yielding the accuracy of 91.7%. CONCLUSIONS We presented a new simple surface ECG algorithm, R-wave deflection interval in lead V3>80 ms combining with R-wave amplitude index in lead V1>0.30 which can reliably distinguish LVOT from RVOT origin in idiopathic outflow tract PVCs/VT in patients with transitional lead at V3.

The amplitude of fibrillatory waves on leads aVF and V1 predicting the recurrence of persistent atrial fibrillation patients who underwent catheter ablation.

To evaluate whether the amplitude of fibrillatory wave (F wave) on electrocardiography could predict the recurrence in persistent atrial fibrillation (AF) patients who underwent catheter ablation.

Characterization of Compacted Myocardial Abnormalities by Cardiac Magnetic Resonance With Native T1 Mapping in Left Ventricular Non-Compaction Patients – A Comparison With Late Gadolinium Enhancement –

BACKGROUND Native T1 mapping is an emerging cardiac magnetic resonance technique for quantitative evaluation of cardiomyopathies. This study aimed to investigate the usefulness of native T1 mapping in characterizing myocardial abnormalities in left ventricular non-compaction (LVNC) by comparing it with late gadolinium enhancement (LGE). METHODSANDRESULTS The study group of 31 LVNC patients and 8 normal controls underwent cardiovascular magnetic resonance to acquire the native T1 maps and LGE images. Of the 31 LVNC patients, 14 had LGE. The mean native T1 value of the normal controls, LGE(-) and LGE(+) patients was 1,098.8±40.8 ms, 1140.6±32.8 ms, and 1181.4±53.7 ms, respectively. Significant differences were found in native T1 between any 2 groups (F=9.74, P<0.001). In discriminating the presence of LGE in LVNC patients, the odds ratio and corresponding 95% confidence interval (CI) of native T1 were, respectively, 2.966 (95% CI: 1.123-7.835, P=0.028) and 4.348 (95% CI: 1.155-16.363, P=0.030) before and after adjusting for confounding factors with an increment of 1 standard deviation. CONCLUSIONS The finding that LGE(-) patients had elevated native T1 compared with normal controls suggested native T1 mapping can be used earlier than LGE imaging to detect myocardial fibrosis in LVNC patients. Furthermore, higher native T1 values in LGE(+) patients than in the LGE(-) group suggested native T1 mapping is more sensitive than LGE imaging for identifying myocardial fibrosis in LVNC patients. (Circ J 2016; 80: 1210-1216).

Left ventricular systolic function and systolic asynchrony in patients with septic shock and normal left ventricular ejection fraction.

ABSTRACT Few studies were performed to investigate the association between tissue Doppler imaging parameters about left ventricular (LV) systolic function and LV systolic asynchrony and prognosis in patients with septic shock and normal LV ejection fraction (LVEF). This prospective study was performed from January 2010 to April 2012 in a medical intensive care unit. Fifty-one patients with septic shock and LVEF greater than or equal to 50% were analyzed. The clinical variables and transthoracic echocardiography data were obtained on admission. The mean value of the peak myocardial systolic velocity (Sm-mean) was measured in the four LV basal segments. Tissue Doppler imaging–based parameter (Ts-SD) was used to evaluate LV intraventricular asynchrony. The 28-day all-cause mortality was 43.1%. The nonsurvivors exhibited higher baseline heart rate and Sm-mean and lower mean arterial blood pressure and Ts-SD. A cutoff value of Sm-mean greater than or equal to 6.2 cm/s in identifying 28-day mortality was determined by the receiver operating characteristic curve analysis. The patients with Sm-mean greater than or equal to 6.2 cm/s or Ts-SD less than 33 ms had higher 28-day mortality. In the Cox multivariate analysis, Sm-mean, Ts-SD, and mean arterial blood pressure emerged as independent predictors for 28-day mortality. We concluded that LV systolic dysfunction and systolic asynchrony assessed by tissue Doppler imaging were associated with improved 28-day all-cause mortality in patients with septic shock and normal LVEF.