Assessment of heart failure and left ventricular systolic dysfunction after cardiac pacing in patients with preserved left ventricular systolic function

BACKGROUND: There is an accumulating data suggesting the deleterious effects of right ventricular pacing on left ventricular performance. Such pacing mimics left bundle branch block resulting in a prolonged QRS duration and causes ventricular asynchrony. AIMS: The purpose of this study is to assess heart failure and left ventricular systolic function after cardiac pacemaker implantation in patients with atrioventricular block and preserved systolic left ventricular function. Secondly, we sought to search for predictive factors of developing left ventricular dysfunction after pacing. METHODS: In this prospective study, we included patients who had been implanted for at least six months. They underwent medical history and examination, 12 leads electrocardiogram and echocardiography before pacemaker implantation and when attending to routine pacemaker follow up. RESULTS: Forty-three patients (22 men and 21 women, age 71+/-12 years) were included in this study. Twenty-nine patients had DDD pacing and 14 VVI pacing. The ventricular lead was implanted in the apex in all patients. After a median follow up of 18+/-11 months, 11 patients (25%) developed signs of congestive heart failure. NYHA was higher after implantation (1.64+/-0.7 versus 2.27+/-0.8, p>0.00001). Left ventricular ejection fraction decreased significantly during follow up (60+/-6% versus 51+/-13%, p=0.0002). Eleven (25%) patients developed left ventricular dysfunction. We compared patients who had left ventricular ejection fraction (LV EF) less or equal to 40% (group A) and patients having LV EF greater than 40% (group B) after implantation. Patients in group A had a paced QRS width significantly larger than group B (181+/-32 ms versus 151+/-26 ms, p=0.002), a significantly prolonged intra left ventricular electromechanical delay (115+/-59 ms versus 45+/-35 ms, p<0.0001) and interventricular delay (44+/-29 ms versus 27+/-18 ms, p=0.02). Age, sex, diabetes hypertension, pacing mode and percentage of ventricular pacing were similar in both groups. A paced QRS width of 180 ms had the best sensitivity and specificity for detecting left ventricular dysfunction: sensitivity=54% and specificity=93%, p=0.01, area under the curve=0.75. CONCLUSION: Patients with atrioventricular block and preserved left ventricular systolic function at baseline decrease significantly left ventricular ejection fraction after pacing. Induced ventricular asynchronism plays a major role in the deterioration of left ventricular function. Prolonged paced QRS width is a good predictor of left ventricular dysfunction after pacing. Larger prospective studies are needed to confirm these data.     

Right ventricular systolic echocardiographic parameters in chronic systolic heart failure and prognosis

BackgroundRight ventricular (RV) dysfunction is associated with poor prognosis in patients with heart failure (HF). Several RV echocardiographic parameters have been proposed as sensitive markers to detect patients at risk.ObjectiveThe aim is to compare the predictive value of several RV systolic echocardiographic parameters for adverse outcome in patients with chronic systolic HF.MethodsWe assessed 117 patients with chronic systolic HF and left ventricular ejection fraction (LVEF) <40% for the following: (i) RV fractional area change (RVFAC), (ii) tricuspid annular plane systolic excursion (TAPSE), (iii) integral of the systolic wave (ISW_tdi), and (iv) peak systolic velocity (Sa_tdi). ISW_tdi and Sa_tdi were measured using tissue Doppler imaging at the tricuspid annulus. The primary endpoint was death, urgent transplantation, or acute HF episode requiring hospital admission. The follow-up extended for one year.ResultsFifty-two patients reached the primary endpoint. The cut-off thresholds for RVFAC, TAPSE, Sa_tdi, and ISW_tdi defined using receiver-operating characteristic curves were 30%, 15.5 mm, 10.0 cm/s, and 2.4 cm, respectively. The area under the curve and the 95% confidence interval for RVFAC, TAPSE, Sa_tdi, and ISW_tdi were 0.71(0.65–0.85), 0.66(0.55–0.76), 0.85(0.70–0.96), and 0.75(0.64–0.86), respectively. NYHA > 2, and Sa_tdi were found to be independent predictors of adverse outcome.ConclusionSa_tdi is an independent predictor of adverse outcome in HF at a threshold value of 10.0 cm/s and appears to be superior to other RV systolic echocardiographic parameters.     

The prevalence of heart failure and asymptomatic left ventricular systolic dysfunction in a typical regional pacemaker population.

AIMS: To assess the prevalence of heart failure and asymptomatic left ventricular systolic dysfunction in the chronically paced population. METHODS AND RESULTS: Three hundred and seven patients were identified from attendance at routine pacemaker follow-up clinic. Subjects underwent a medical history and examination, 6-minute walk test and echocardiography. 94 (31%) had a left ventricular ejection fraction (LVEF) <40%, of whom 83 had symptoms of heart failure (70% NYHA II, 26% NYHA III and 4% NYHA IV). Heart failure was more prevalent in patients with single chamber compared to dual chamber pacemakers, (DDD(R) 18% vs 35% VVI(R), p<0.008), and those with chronic atrial fibrillation (AF) compared to those with sinus rhythm (42% vs 21%, p=0.003). Decreasing 6-minute walk distance, history of ischaemic heart disease and years of pacing were independently associated with the presence of heart failure (combined R=0.572, p<0.001). CONCLUSIONS: Heart failure due to left ventricular systolic dysfunction is common in the paced population. Only a minority of these had a pre-existing diagnosis and a smaller proportion were on 'optimal' therapy. Echocardiographic screening of this high-risk population is justified to improve rates of diagnosis and treatment of heart failure.     

Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection fraction: The VICTORIA echocardiographic substudy

Aim

Vericiguat significantly reduced the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death in the VICTORIA trial. It is unknown if these outcome benefits are related to reverse left ventricular (LV) remodelling with vericiguat in patients with HF with reduced ejection fraction (HFrEF). The aim of this study was to compare the effects of vericiguat versus placebo on LV structure and function after 8 months of therapy in patients with HFrEF.

Methods and results

Standardized transthoracic echocardiography (TTE) was performed at baseline and after 8 months of therapy in a subset of HFrEF patients in VICTORIA. The co-primary endpoints were changes in LV end-systolic volume index (LVESVI) and LV ejection fraction (LVEF). Quality assurance and central reading were performed by an echocardiographic core laboratory blinded to treatment assignment. A total of 419 patients (208 vericiguat, 211 placebo) with high-quality paired TTE at baseline and 8 months were included. Baseline clinical characteristics were well balanced between treatment groups and echocardiographic characteristics were representative of patients with HFrEF. LVESVI significantly declined (60.7 ± 26.8 to 56.8 ± 30.4 ml/m²; p < 0.01) and LVEF significantly increased (33.0 ± 9.4% to 36.1 ± 10.2%; p < 0.01) in the vericiguat group, but similarly in the placebo group (absolute changes for vericiguat vs. placebo: LVESVI −3.8 ± 15.4 vs. −7.1 ± 20.5 ml/m²; p = 0.07 and LVEF +3.2 ± 8.0% vs. +2.4 ± 7.6%; p = 0.31). The absolute rate per 100 patient-years of the primary composite endpoint at 8 months tended to be lower in the vericiguat group (19.8) than the placebo group (29.6) (p = 0.07).

Conclusions

In this pre-specified echocardiographic study, significant improvements in LV structure and function occurred over 8 months in both vericiguat and placebo in a high-risk HFrEF population with recent worsening HF. Further studies are warranted to define the mechanisms of vericiguat's benefit in HFrEF.     

左室射血分数正常的心力衰竭患者的临床特点及左室收缩功能

目的 应用超声测量左室射血分数(LVEF)正常的心力衰竭(心衰)患者的房室平面位移,观察该类患者是否存在心室长轴方向收缩功能异常.方法 收集住院心衰患者96例,LVEF正常心衰组和LVEF降低心衰组各48例,50例健康体检者入选为对照组.比较各组在NYHA心功能分级、基础病因、房室平面位移、血浆N末端B型利钠肽原浓度的差异.结果 LVEF正常心衰组和LVEF降低心衰组的NYHA心功能分级差异无统计学意义.LVEF正常心衰组常见病因为高血压性心脏病和冠心病.对照组、LVEF正常心衰组、LVEF降低心衰组的房室平面位移依次下降.房室平面位移与血浆N末端B型利钠肽原水平负相关(r=-0.35,P<0.05).结论 通过传统方法测定的LVEF正常心衰组患者存在心室长轴方向上的收缩功能异常,而非单纯的舒张性心衰.     

Effects of nebivolol on left ventricular function in elderly patients with chronic heart failure: results of the ENECA study

AIM: To examine the effect of the beta(1)-selective beta-blocker nebivolol, administered as add-on therapy, on left ventricular function in 260 elderly patients (>65 years) with chronic heart failure (CHF). METHODS: The principal inclusion criteria were (1) NYHA class II-IV CHF and (2) a left ventricular ejection fraction (LVEF) <= 35%. The primary end-point was the change in LVEF in response to nebivolol treatment for 8 months. RESULTS: Baseline LVEF values in the two groups were as follows: nebivolol 25.41+/-7.09% and control 26.41+/-5.55%. LVEF improved significantly (p=0.027) more in the nebivolol group (6.51+/-9.15%) than in the control group (3.97+/-9.20%), the relative improvement (percentage increase in the initial value) being 35.70+/-57.62% in the nebivolol group and 19.19+/-40.96% (p=0.008) in the placebo group. Examination of different subgroups did not reveal any heterogeneity in the effects of nebivolol treatment vs. placebo treatment. There were no significant differences between the nebivolol and placebo groups as concerns the changes in clinical status, quality of life, or safety parameters. CONCLUSION: The findings of the ENECA study confirmed that nebivolol significantly improved cardiac function and proved to be safe and well tolerated in elderly patients with signs of CHF and an impaired LVEF.     

Echocardiographic indices of left ventricular diastolic dysfunction in 647 individuals with preserved left ventricular systolic function

BACKGROUND: Knowledge about the occurrence of isolated diastolic dysfunction (DD) in the general population is limited. AIMS: This population study was performed to assess the frequency and distribution pattern of echocardiographic indices of left ventricular (LV) DD in an elderly population aged 50-89 years in which LV systolic function is preserved. METHODS AND RESULTS: The study population (n=764) recruited from the background population answered a heart failure questionnaire and underwent echocardiography. Excluding subjects with a LV ejection fraction <50% or atrial fibrillation, diastolic function was evaluated in 647 subjects. The frequency of impaired relaxation according to earlier guidelines was 0.5%, vs. 2.5% using age- and gender-specific normal values of 'E/A-ratio' and 'deceleration time'. In a subpopulation of 167 participants, 6.6% had 'pseudonormalisation'. No difference was found in the frequency of dyspnea in subjects with impaired relaxation or 'pseudonormalisation' compared to subjects with normal filling pattern. CONCLUSION: The prevalence of LV impaired relaxation was highly dependent on the choice of normal (cut-off) values for Doppler indices. Furthermore, our findings suggest that either isolated DD is often asymptomatic, or that Doppler flow derived parameters as a diagnostic method for assessing DD have a low specificity when used as a screening tool in the general population.     

老年舒张性心力衰竭与收缩性心力衰竭患者左心形态及功能的超声评价

目的　探讨老年舒张性心力衰竭与收缩性心力衰竭患者超声左心形态、功能的特点。方法　对临床确诊的 30例老年左心室舒张性心力衰竭 (L VDHF)病例及 36例老年左心室收缩性心力衰竭 (L VSHF)病例进行超声检测 ,以2 0例正常人为对照组。结果　 1与 L VSHF组比较 ,L VDHF组左心房内径 (L AD)、左心室内径 (L VD)扩大程度小 ,但室间隔厚度 (IVST)、左心室后壁厚度 (PWT)增加。 2与对照组比较 ,L VDHF组 L AD、IVST、PWT增加 ,但L VD无显著性差异 ,L VSHF组 L VD显著性扩大。 3L VDHF组左心室射血分数 (L VEF)、心脏指数 (CI)与对照组比较无显著差异 ,而 L VSHF组 L VEF、CI减低。4与对照组比较 ,L VDHF组二尖瓣舒张早期流速峰值 (EPFV)、二尖瓣舒张早、晚期流速峰值比 (E/ A )、舒张早期减速度 (DC)减低 ,二尖瓣舒张晚期流速峰值 ((APFV )、等容舒张时间 (IRT)增高。L VDHF组上述指标与 L VSHF组无显著差异。结论　难以单纯从超声左心室舒张功能指标判断有无 L VDHF的存在 ,应综合分析判断。     

NT-proBNP levels, echocardiographic findings, and outcomes in breathless patients: results from the ProBNP Investigation of Dyspnoea in the Emergency Department (PRIDE) echocardiographic substudy.

AIMS: The objective of this study was to determine the integrative utility of measuring plasma NT-proBNP levels with echocardiography in the evaluation of dyspnoeic patients. METHODS AND RESULTS: Of 599 emergency department patients enrolled in a clinical study of NT-proBNP at a tertiary-care hospital, 134 (22%) had echocardiographic results available for analysis. Echocardiographic parameters correlating with NT-proBNP levels were determined using multivariable linear-regression analysis. Independent predictors of 1-year mortality were determined using Cox-proportional hazard analysis. Independent relationships were found between NT-proBNP levels and ejection fraction (P = 0.012), tissue Doppler early and late mitral annular diastolic velocities (P = 0.007 and 0.018), right ventricular (RV) hypokinesis (P = 0.006), and tricuspid regurgitation severity (P < 0.001) and velocity (P = 0.007). An NT-proBNP level <300 pg/mL had a negative predictive value of 91% for significant left ventricular systolic and diastolic dysfunction. Overall 1-year mortality was 20.1% and was independently predicted by NT-proBNP level [HR 8.65, 95% confidence interval (CI) 2.7-27.8, P = 0.0003], ejection fraction (HR 0.95, 95% CI 0.91-0.99, P = 0.009), RV dilation (HR 2.98, 95% CI 1.05-12.8, P = 0.04), and systolic blood pressure (HR 0.97, 95% CI 0.96-0.99, P = 0.01). CONCLUSION: NT-proBNP levels correlate with, and provide important prognostic information beyond, echocardiographic parameters of cardiac structure and function. Routine NT-proBNP testing may thus be useful to triage patients to more timely or deferred echocardiographic evaluation.     

Matrix metalloproteinase-1 and -2 levels are differently regulated in acute exacerbation of heart failure in patients with and without left ventricular systolic dysfunction

Matrix metalloproteinases (MMPs) play important roles in progression of chronic heart failure (HF) by regulating cardiac extracellular matrix metabolism. However, there is no report to investigate the difference of circulating MMP-1 and MMP-2 levels between systolic HF (SHF) and diastolic HF (DHF), particularly in light of acute exacerbation of HF. We assessed 110 HF patients who were admitted because of an acute exacerbation. They were divided into two groups: SHF [n = 68, left ventricular ejection fraction (LVEF) <45%] or DHF (n = 42, LVEF ≥45%). Ten patients without HF served as controls. Serum MMP-1 and MMP-2, and plasma brain natriuretic peptide (BNP) levels were examined on admission and at discharge. Serum MMP-1 level was higher on admission in both SHF and DHF than in controls. It was higher in SHF than in DHF and did not change at discharge in both groups. Serum MMP-2 level was equally higher on admission in SHF and DHF than in controls. It decreased in both groups at discharge. Treatment-induced changes in LVEF and BNP level correlated with those in MMP-2 level in SHF but not in DHF. Circulating MMP-1 and MMP-2 levels showed different dynamics between SHF and DHF in acute exacerbation and after treatment. These differences in circulating MMP-1 and MMP-2 levels may be related to the phenotype of HF.     

Effects of carvedilol on left ventricular remodeling and systolic function in elderly patients with heart failure

BACKGROUND: Recent studies have shown that carvedilol therapy in patients with heart failure improves clinical outcome and survival, however, the effects of such treatment on left cardiac morphology and function in elderly patients with severe heart failure has not been widely studied. AIM: The purpose of this study was to establish the effect of carvedilol at short- and long-term on left ventricular size and performance with mono- and two-dimensional echocardiography, in subjects with dilated cardiomyopathy, NYHA III functional class, low LV ejection fraction (EF < 35%) and mean age of > 70 years. METHODS: We studied 48 patients, previously randomized to treatment with either carvedilol or placebo, and we performed echocardiographic evaluation at the start, and after 3 and 12 months. Left ventricular diameters, LV mass and fractional shortening were calculated by Deveraux formula; left ventricular volumes and ejection fraction were measured by area-length formula; pulmonary pressure was calculated by tricuspid reflow. RESULTS: After 3 months, only LV end-diastolic diameter was lower in the carvedilol group compared to the placebo group. Nevertheless, after 12 months, patients on carvedilol treatment showed a LV geometric and functional improvement compared to placebo. We found significant differences in: diastolic (P < 0.01) and systolic diameters (P < 0.001); on LV mass (P < 0.002); on LV systolic volume (P < 0.03); and on LV ejection fraction (P<0.01). Pulmonary pressure was also reduced in beta-blocker subjects (P < 0.001). CONCLUSIONS: Carvedilol therapy for 12 months reduced LV diameters and volumes. Thus, improving cardiac remodeling and LV systolic function in elderly patients with severe heart failure. Several months of therapy are required for these favorable effects to occur, as these changes do not occur in the short term.     

Prognostic impact of matrix metalloproteinase gene polymorphisms in patients with heart failure according to the aetiology of left ventricular systolic dysfunction.

AIMS: To assess the possible effect of functional polymorphisms in matrix metalloproteinase (MMP) gene promoters on the clinical outcome of patients with heart failure. METHODS AND RESULTS: We studied 444 consecutive patients who were referred to our centre for evaluation of left ventricular dysfunction. We extracted genomic DNA from white blood cells and determined the -1306 C >T MMP-2, -1171 5A > 6A MMP-3, and -1562 C >T MMP-9 polymorphisms. Clinical follow-up (median 717 days) was obtained for 443 patients. The MMP-3 polymorphism had a different impact on cardiac survival in HF patients with ischaemic and non-ischaemic cardiomyopathy (interaction p <0.03). The MMP-3 5A/5A genotype was an independent predictor of cardiac mortality (HR 2.92 [1.23-6.69]; p = 0.01) in patients with non-ischaemic HF. In contrast, there was no evidence for any effect of the MMP-3 genotype on cardiac events in patients with ischaemic cardiomyopathy. The MMP-9 polymorphism was associated with cardiac survival (p < 0.03) independently of HF aetiology. In multivariate analysis, the MMP-9 T allele was an independent predictor of cardiac mortality (HR 1.81 [1.09-3.02]; p = 0.02). Finally, there was no evidence for any association between MMP-2 polymorphism and cardiac survival. CONCLUSION: MMP-3 and MMP-9 polymorphisms contribute to variability in cardiac survival in HF patients. These data suggest that MMP genotyping could provide important additional information for refining risk stratification in patients with heart failure. MMP genotyping may help to select patients who could benefit from MMP inhibition.     

Prevalence and predictors of anxiety and depression in a sample of chronic heart failure patients with left ventricular systolic dysfunction

OBJECTIVE: To determine the prevalence and predictors of anxiety and depression in patients with heart failure due to Left Ventricular Systolic Dysfunction (LVSD). BACKGROUND: Psychological adjustment to Chronic Heart Failure (CHF) can be poor, with the prevalence of depression in out-patients ranging from 13% to 48%. The prevalence of anxiety disorders in this population is unknown and the factors that predict anxiety and depression are not well understood. METHODS: 100 out-patients from a community heart failure programme completed a clinical diagnostic interview--the Structured Clinical Interview (SCID-I), to evaluate anxiety and depression. Mean age was 67+/-11 years, 17% were women and 91% were NYHA Class II or III. Other standardised measures were of cognition, biomedical status, social support and previous physical and mental health history. RESULTS: The prevalence rates of anxiety and depression (all subtypes) were 18.4% and 28.6%, respectively. Predictors of depression included a reported history of mental ill-health and NYHA class. Predictors of anxiety included a reported history of mental ill-health, co-morbid physical illness (diabetes and angina) and NYHA class. Severity of LVSD did not predict either anxiety or depression. CONCLUSIONS: Both anxiety and depression are common in CHF patients. The data on the predictors of poor psychological adjustment might assist in targeting bio-psychosocial intervention for patients who are at most at risk of anxiety and depression, within community CHF disease management programmes.     

Correlation with invasive left ventricular filling pressures and prognostic relevance of the echocardiographic diastolic parameters used in the 2016 ESC heart failure guidelines and in the 2016 ASE/EACVI recommendations: a systematic review in patients with heart failure with preserved ejection fraction

Aims

Five echocardiographic parameters—left atrial volume index, left ventricular mass index, tricuspid regurgitation velocity, myocardial tissue velocity, and the ratio of early mitral inflow to tissue velocity of the mitral annulus (E/e')—are recommended in both the current European Society of Cardiology heart failure guidelines and the American Society of Echocardiography/European Association of Cardiovascular Imaging recommendations for the evaluation of left ventricular diastolic function. We aimed to perform a systematic review of these echocardiographic parameters at resting conditions for their correlation with left ventricular filling pressures in patients with heart failure with preserved ejection fraction (HFpEF). In addition, the prognostic value of these parameters was assessed.

Methods and results

Nine studies reported the correlation between echocardiography and invasive haemodynamics, and 18 papers reported on the prognostic value of echocardiography in HFpEF. Among the parameters, most data were reported for E/e'. The pooled correlation coefficient r was 0.56 for the relation between E/e' and invasively measured filling pressures. Combined weighted‐mean meta‐analysis of prognostic studies resulted in a hazard ratio of 1.05 (95% confidence interval 1.03–1.06) per unit increase in E/e' for the combined outcome of all‐cause mortality and cardiovascular hospitalization. The other echocardiographic parameters, when taken individually, had similar or lower association with prognosis.

Conclusion

Only a small number of studies validated the use of echocardiographic parameters at rest in patients with HFpEF. The best established parameter appears to be E/e', but the existing data only show modest correlations of E/e' with invasive filling pressures and outcomes in HFpEF.