Left Ventricular Assist Devices: A Primer For the General Cardiologist.

Durable implantable left ventricular assist devices (LVADs) have been shown to improve survival and quality of life for patients with stage D heart failure. Even though LVADs remain underused overall, the number of patients with heart failure supported with LVADs is steadily increasing. Therefore, general cardiologists will increasingly encounter these patients. In this review, we provide an overview of the field of durable LVADs. We discuss which patients should be referred for consideration of advanced heart failure therapies. We summarize the basic principles of LVAD care, including medical and surgical considerations. We also discuss the common complications associated with LVAD therapy, including bleeding, infections, thrombotic issues, and neurologic events. Our goal is to provide a primer for the general cardiologist in the recognition of patients who could benefit from LVADs and in the principles of managing patients with LVAD. Our hope is to "demystify" LVADs for the general cardiologist.

Right atrial volume index to left atrial volume index ratio is associated with adverse clinical outcomes in cardiogenic shock.

BACKGROUND: Structural remodeling in chronic systolic heart failure (HF) is associated with neurohormonal and hemodynamic perturbations among HF patients presenting with cardiogenic shock (CS) and HF. Our objective was to test the hypothesis was that atrial remodeling marked by an increased right atrial volume index (RAVI) to left atrial volume index (LAVI) ratio is associated with adverse clinical outcomes in CS. METHODS: Patients in this cohort were admitted to the intensive care unit with evidence of congestion (pulmonary capillary wedge pressure > 15) and cardiogenic shock (cardiac index < 2.2, systolic blood pressure < 90 mmHg, and clinical evidence supporting CS) and had an echocardiogram at the time of admission. RAVI was measured using Simpson's method in the apical four-chamber view, while LAVI was measured using the biplane disc summation method in the four and two-chamber views by two independent observers. Cox proportional hazards regression analysis was used to assess the association of RAVI-LAVI with the combined outcome of death or left ventricular assist device (LVAD). RESULTS: Among 113 patients (mean age 59 ± 14.9 years, 29.2% female), median RAVI/LAVI was 0.84. During a median follow-up of 12 months, 43 patients died, and 65 patients had the combined outcomes of death or LVAD. Patients with RAVI/LAVI ratio above the median had a greater incidence of death or LVAD (Log-rank p ≤ 0.001), and increasing RAVI/LAVI was significantly associated with the outcomes of death or LVAD (HR 1.71 95% CI 1.11-2.64, chi square 5.91, p = 0.010) even after adjustment for patient characteristics, echocardiographic and hemodynamic variables. CONCLUSION: RAVI/LAVI is an easily assessed novel echocardiographic parameter strongly associated with the survival and or the need for mechanical circulatory support in patients with CS.

Short-term efficacy and safety of levosimendan in patients with chronic systolic heart failure.

The objective was to investigate and evaluate the short-term efficacy and safety of levosimendan in patients with chronic systolic heart failure. Forty-nine patients with chronic systolic heart failure during acute decompensation were randomly divided into a levosimendan group (26 cases) and a control group (23 cases). The control group received only routine treatment, while the levosimendan group received a levosimendan bolus with a load of 12 µg/kg, in addition to the same routine treatment as the control group. After 48 hours of treatment, N-terminal pro B-type natriuretic peptide (NT-proBNP) levels in the levosimendan group were significantly lower than those in the control group. In addition, the left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) cardiac function scores of the levosimendan group were significantly higher and more improved than those of the control group seven days after treatment, but there was no significant difference in the left ventricular end-diastolic diameter between the two groups. Furthermore, 48 hours after treatment, there were no significant differences in potassium, haemoglobin, haematocrit and creatinine levels between the levosimendan and control groups. During the whole hospitalisation, there was one case of sudden death in the control group and one case of palpitations in the levosimendan group, and no hypotension or severe hypokalaemia occurred in either group. Levosimendan significantly improved NT-proBNP and LVEF in patients with chronic systolic heart failure, and improved NYHA cardiac function classification without significant cardiovascular events. Levosimendan is therefore effective and safe in the short-term treatment of chronic systolic heart failure.

MicroRNA-183-3p up-regulated by vagus nerve stimulation mitigates chronic systolic heart failure via the reduction of BNIP3L-mediated autophagy.

Chronic systolic heart failure (CSHF) was a complex syndrome. Recently, vagus nerve stimulation (VNS), a novel treatment method, has emerged for the treatment of CSHF. therefore the aim of this study was to explore the possible mechanism of VNS treatment alleviating CSHF in rats. Firstly, we found after VNS treatment for 72 h, the level of B-type natriuretic peptide in VNS group was lower than that in CSHF group. In addition, VNS treatment induced the elevated left ventricular ejection fraction level, reduced left ventricular end diastolic volume and left ventricular end systolic volume level in VNS group, suggesting a mitigation of CSHF by VNS. Then we found the level of miR-183-3p in CSHF group was much lower than that in VNS group by High-throughput sequencing. The further results indicated that Bcl-2 interacting protein 3 like (BNIP3L) was identified as the target gene of miR-183-3p, and the expression of BNIP3L was notably reduced in rats of VNS group compared with CSHF group. Moreover, the down-regulated expression of miR-183-3p increased BNIP3L-mediated autophagy in rats of CSHF group compared with VNS group. Further mechanism findings demonstrated that up-regulation of miR-183-3p reduced the expression of BNIP3L, while down-regulation of miR-183-3p facilitated the expression of BNIP3L in H9c2 cells. miR-183-3p could also regulate autophagy by targeting BNIP3L in vitro, which was manifested by overexpression of miR-183-3p to inhibit BNIP3L-mediated autophagy. Our data demonstrated that VNS treatment benefited CSHF via the up-regulation of miRNA-183-3p, which reduced the BNIP3L-mediated autophagy, providing a new therapeutic direction for CSHF.

Pulse pressure and prognosis in patients with heart failure with reduced ejection fraction.

BACKGROUND: A high pulse pressure (PP) is associated with adverse cardiovascular (CV) outcomes; however, this relationship may be reversed in patients with heart failure with reduced ejection fraction (HFREF). METHODS: Patients from the WARCEF trial with left ventricular ejection fraction ≤35% were included. PP was divided into tertiles: ≤42, 42-54 and >54 mm Hg. Age and ejection fraction adjusted Kaplan-Meier curves were generated to evaluate the relationship between PP and outcomes [mortality, CV mortality, stroke and HF hospitalizations (HFH)]. Cox proportional hazards models were created incorporating PP as a continuous variable. The interaction of PP with New York Heart Association (NYHA) functional class was examined. Linear and restricted cubic splines were used to study nonlinear association between PP and outcomes. RESULTS: We included 2,299 patients with a mean(±SD) follow-up of 3.5 ± 1.8 years. The lowest tertile of PP (≤42 mm Hg) was associated with significantly higher CV mortality and HFH. Cox proportional hazards models showed a reduction in CV death and HFH with higher PP, with adjusted hazard ratios (HR) of 0.91 (P = 0.02) and 0.93 (P = 0.04) per 10 mm Hg increase in PP. This relationship was more pronounced in subjects with NYHA functional class III-IV. Spline analysis showed that the association between PP and CV mortality and HFH was only seen at PP values lower than 40 mm Hg. CONCLUSIONS: In patients with advanced HFREF, a low PP (<40 mm Hg) portends a worse prognosis, whereas a high PP (>50 mm Hg) predicts a relatively favourable prognosis.

Etiology-specific assessment of predictors of long-term survival in chronic systolic heart failure.

BACKGROUND: We sought to identify prognostic factors of long-term mortality, specific for the underlying etiology of chronic systolic heart failure (CHF). METHODS AND RESULTS: Between 1995 and 2009 baseline characteristics, treatment and follow-up data from 2318 CHF-patients due to ischemic (ICM; 1100 patients) or dilated cardiomyopathy (DCM; 1218 patients) were prospectively compared. To calculate hazard ratios with 95%-confidence intervals cox regression was used. We respectively established etiology-specific multivariable models of independent prognostic factors. During the follow-up period of up to 14.8 years (mean = 53.1 ± 43.5 months; 10,264 patient-years) 991 deaths (42.8%) occurred. In the ICM-cohort, 5-year-survival was 53.4% (95% CI: 49.9-56.7%), whereas in DCM-patients it was higher (68.1% (95% CI: 65.1-71.0%)). Age, ejection fraction, or hyponatremia were independent predictors for mortality in both cohorts, whereas diabetes, COPD, atrial fibrillation and a heart rate of ≥ 80/min carried independent predictive power only in ICM-patients. CONCLUSION: This study demonstrates the disparity of prognostic value of clinically derived risk factors between the two main causes of CHF. The effects of covariables in DCM-patients were lower, suggesting a less modifiable disease through risk factors considering mortality risk. An etiology-specific prognostic model may improve accuracy of survival estimations in CHF.

Five-year survival of patients with chronic systolic heart failure of ischemic and non-ischemic etiology: analysis of prognostic factors.

INTRODUCTION: Despite advances in pharmacotherapy, electrotherapy and interventional treatment, chronic heart failure (HF) is still associated with poor long-term outcome. AIM OF THE STUDY: To determine the death rate and risk factors in patients with HF of ischemic and non-ischemic etiology in five-year follow-up. MATERIAL AND METHODS: Consecutive patients with chronic systolic HF hospitalized in the period 2006-2008 were analyzed retrospectively. Study exclusion criteria were: infections (< 3 months before hospitalization), hemodynamically significant valve disease, advanced chronic kidney disease, liver cirrhosis and neoplastic diseases (< 5 years before hospitalization). RESULTS: The analysis encompassed 266 patients divided into two groups: Group A, with HF of ischemic etiology (n = 157), and Group B, with HF of non-ischemic etiology (n = 109). Mortality was significantly higher in Group A than in Group B (49% vs. 28.4%, p = 0.001). The independent risk factors for death in Group A were: New York Heart Association (NYHA) class (HR = 1.81; p < 0.001); concentrations of high-sensitivity C-reactive protein (hs-CRP) (HR = 1.01; p < 0.05), fibrinogen (HR = 1.04; p < 0.001) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) (HR = 1.02; p < 0.001); and right ventricular end-diastolic diameter (RVEDd) (HR = 1.07; p < 0.01). In Group B they were age (HR = 1.07; p < 0.05) and NT-proBNP concentration (HR = 1.03; p < 0.001). CONCLUSIONS: Mortality was significantly lower in Group B than in Group A. The independent risk factors for death in Group B were age and NT-proBNP serum concentration, whilst in Group A they were NYHA class, serum concentrations of hs-CRP, NT-proBNP and fibrinogen, and RVEDd.

The seasonal variation in hospitalizations due to chronic systolic heart failure correlates with blood sodium levels and cardiac function.

BACKGROUND: Although seasonal variation in hospitalizations due to chronic heart failure is recognized, the possible contributors to such variability are less well documented. METHODS: Records from all admissions to 12 hospitals in Hubei province, China, over a 10-year period with diagnostic codes for chronic systolic heart failure (CSHF) were reviewed. A total of 16,145 patients with CSHF were analyzed. RESULTS: There was a marked seasonal variation in the number of hospitalizations due to CSHF, with two peaks in the monthly rate of hospitalization due to CSHF occurring in December and August compared with the spring and autumn months. Monthly hospitalizations due to CSHF for patients with New York Heart Association class III and IV ranged from a peak of 40.4% and 23.3% above average in December and August, respectively, to 18.6% below average in November, while hospitalizations due to CSHF for patients with New York Heart Association class I and II exhibited no obvious seasonal variation. Blood sodium level (95% CI 2.132 to 2.144; P=0.036) was an independent risk factor for hospitalizations due to CSHF in August. CONCLUSION: The number of hospitalizations due to CSHF increased during the colder and warmer months in China. A low blood sodium level was associated with the peak in hospitalizations in August.

Haemodynamic response during low-dose dobutamine infusion in patients with chronic systolic heart failure: comparison of echocardiographic and invasive measurements.

AIMS: To investigate whether left ventricular (LV) systolic shortening velocity (s'), diastolic lengthening velocity (e'), and non-invasively estimated LV filling pressure (E/e') during low-dose dobutamine echocardiography (LDDE) reflect invasive measures of cardiac output and pulmonary capillary wedge pressure (PCWP) in stable patients with chronic systolic heart failure. METHODS AND RESULTS: Fourteen patients with heart failure (aged 65 ± 8 years, LVEF 36 ± 8%) underwent simultaneous tissue Doppler echocardiography and invasive measurements of cardiac output and PCWP by right heart catheterization at rest and during dobutamine infusion at rates of 10 and 20 µg/kg/min. Cardiac output increased from rest to peak dobutamine (4.9 ± 1.2 to 6.6 ± 2.0 L/min, P < 0.001) and correlated with the peak systolic tissue velocity (s') at rest (R = 0.61, P = 0.02) and during dobutamine stimulation (R = 0.79, P < 0.001). Increases in early diastolic mitral inflow (E, 74.9 ± 29.0-90.8 ± 29.5 cm/s) and LV lengthening (e', 6.5 ± 2.4-8.2 ± 2.8 cm/s) velocities were observed during LDDE leaving the E/e' ratio unchanged. Although a mean PCWP was also unchanged from rest to peak dobutamine (16.6 ± 8.3-14.2 ± 9.2, P = 0.25), E/e' and PCWP only correlated at rest (R = 0.64, P = 0.014). CONCLUSION: The LV systolic shortening velocity is closely associated with cardiac output during LDDE in CHF patients. Dobutamine stimulation increases early diastolic mitral inflow and lengthening velocities, but the E/e' ratio does not reflect the PCWP during LDDE, which warrants some caution in converting changes in E/e' into changes in LV filling pressure. The sample size is, however, small and the observation need to be confirmed in a larger population.

Investigation on the prevalence and related factors of medicinal therapy in patients with chronic svstolic heart failure / 中华流行病学杂志

Objective To investigate the prevalence and related factors of medicinal therapy in patients with chronic systolic heart failure (CSHF).Methods Data on in-hospital patients with CSHF were studied from 12 hospitals in Hubei province,in 2000 and 2010.Differences on gender and age were calculated and Multivariate Cox regression analysis was performed to determinate the independent risk factors of all-cause mortality.Results (1) 16 681 patients were enrolled in this study.Among which,6453 died during the 5.82 ± 1.63 years of follow-up.The annual medical expenditure was larger in the survival group than in the dead ones (3.19 ± 0.65 vs.3.32 ± 0.57,P＜0.01).(2)The prevalence of Angiotensin Ⅱ receptor blocker increased along with age which accounted as 7.73％,7.35％,12.26％,14.29％,17.19％,19.87％ and 20.49％,respectively,in the ＜30,30-39,40-49,50-59,60-69,70-79 and ≥80-year groups.The distribution of digitalis,diuretics,β-receptor blocker,Angiorensin- converting enzyke inhibitors showed inversed U shape.(3)The annual medical expenditure increased as patients got older,with age groups ＜30,30-39,40-49,50-59,60-69 and 70-79 years old as 2.96 ± 0.70,3.09 ± 0.62,3.15 ± 0.58,3.30 ± 0.59 and 3.25 ±0.58,respectively (P＜0.01).It reduced to the same level as in the 50-59 year-old group.The distribution of annual medical expenditure showed similar pattern in males.However,the trends were only found in patients at 50-59,60-69,70-79 and ≥80 years-old groups in female.Conclusion More attention should be paid to medicinal therapy in patients with CSHF.Medicinal therapy shifted with age and gender,of which females had more adverse trend than in males.

The prognostic value of etiology in patients with chronic systolic heart failure / 中华流行病学杂志

Objective To determinate the prognostic value of etiology in patients with chronic systolic heart failure (CSHF).Methods Data of in-hospital patients with CSHF were investigated between 2000 and 2010 from 12 hospitals in Hubei province.All patients were followed up through telephone calls.Univariate and multivariate Cox proportional hazards analyses were then used to explore the differences in the all-cause mortality,heart failure (HF) mortality and sudden cardiac death (SCD) among patients caused by different etiologies.Kaplan-Meier curve were then constructed and Univariate and multivariate Cox regression analyses were used to select demographic and clinical variables in predicting the all-cause mortality,HF mortality and SCD in CSHF patients.Multivariate logistic models and ROC curve were developed with or without the cinfirmed etiology to assess the incremental additive information related to different etiologies.Results (1)Over the median 3 (2-4) years follow-up program,6453 (38.69％) patients died,including 5505 (33.00％) due to HF prognosis and 717 (4.30％) died of SCD.All-cause mortality rates accounted for 34.50％,54.30％,41.48％ and 15.76％,with HF mortality rates as 30.11％,44.95％,36.25％ and 13.10％.SCDs accounted 8.46％,8.45％,9.84％ and 1.05％ in patients with CHD,DCM,HHD and RHD,respectively.(2) Compared with RHD patients,the adjusted HRs for all-cause mortality were 1.554 (1.240 to 1.947;P＜0.001),1.405(1.119 to 1.764;P=0.003) and 1.315(1.147 to 1.467;P=0.005) while the adjusted HRs and 95％CIs for HF mortality were 1.458( 1.213-1.751 ;P＜0.001 ),1.763( 1.448-2.147;P＜0.001 ) and 1.281 ( 1.067-1.537; P=0.008),in patients with CHD,DCM and HHD,respectively.There were no significant differences in CHD (HR 3.345; 95％ CI,1.291 to 8.666; P=0.013 ) or HHD (HR 2.062; 95％CI,0.794 to 5.352; P=0.137 ),while only DCM ( HR 4.764; 95％CI,1.799 to 12.618;P=0.002) remained significant in SCD despite of the multivariate adjustment.(3) Etiology increased the sensitivity and specificity of predicting models for all-cause mortality(AUC 0.839,95％CI,0.832to 0.845 vs.0.776,95％CI,0.768 to 0.784) and HF mortality(AUC 0.814,95％CI,0.806 to 0.822 vs.0.796,95％CI,0.788 to 0.804) but not with SCD (AUC 0.777,95％CI,0.749 to 0.809 vs.0.747,95％CI,0.727 to 0.766).Conclusion CSHF due to CHD,DCM and HHD carried a worse prognosis than that of RHD.Different etiologies provided significant incremental prognostic information beyond readily available clinical variables for all-cause mortality and HF mortality.

Relationship between the level of uric acid and oxidative stress in patients with chronic systolic heart failure / 中国医师进修杂志

Objective To study the relationship between the level of uric acid and oxidative stress in patients with chronic systolic heart failure (CSHF). Methods One hundred and nine hospitalized patients from June 2006 to March 2007 were selected. Based on organic heart disease and heart function, they were classified into two groups: CSHF group (81 cases) and control group (28 eases). According to NYHA heart function grade (Ⅱ, Ⅲ, Ⅳ), CSHF group was divided into three subgroups. The plasma concentration of GSH and GSSG was determined by using glutathione reduetase recycling method (GR-DTNB). Redox potential (Eh) was calculated using Nemst equation according to the concentration of reduced and oxidized glutathione. Results There was significant difference between control group and CSHF group in the level of uric acid [(310.54±99.92) μ mol/L vs (499.09±168.04) μ mol/L], P < 0.01. Uric acid had a negative correlation with LVEF (r=-0.247, P=0.026), and a positive correlation with LVED D (r=0.266, P=0.016). The concentration of uric acid had a negative correlation with GSH (r=-0.328,P=0.003), and a positive correlation with GSSG (r=0.244, P=0.028) and Eh (r=0.309, P=0.005). Conclusions The concentration of uric acid increases in CSHF patients and has a correlation with LVEF and LVEDD. It may be a supplementary marker to reflect heart function and the serious degree of CSHF. The concentration of uric acid has a negative correlation with GSH, and a positive correlation with GSSG and the value of Eh. It may be used as an indicator of oxidative stress concerning its metabolic pathway.