High-sensitivity C-reactive protein and atherosclerosis: from theory to therapy

Atherosclerosis remains the leading cause of morbidity and mortality in Western countries. Recent evidence has demonstrated that atherosclerosis is not simply a disease of lipid deposition. Inflammation plays a major role in the initiation, progression, and destabilization of atheromas. High-sensitivity C-reactive protein (hs-CRP) is a circulating acute-phase reactant that reflects active systemic inflammation. Large prospective trials have shown hs-CRP to be a strong predictor of future cardiovascular events. Increased hs-CRP concentration is in fact associated with higher cardiovascular events in individuals with and without clinical evidence of atherosclerotic disease. The relative risk associated with hs-CRP is independent of other cardiovascular disease risk factors. Assays for hs-CRP measurement are currently available but must be standardized because patients’ results will be interpreted by using population-based cutpoints. A risk-stratifying algorithm incorporating hs-CRP and total cholesterol to high-density lipoprotein cholesterol ratio has been proposed. Further research into the mechanisms and pharmacological treatment of vascular disease will provide novel management strategies in the very near future.     

Gene therapy to restore electrophysiological function in heart failure

Introduction: Heart failure (HF) is a major public health epidemic and a leading cause of morbidity and mortality in the industrialized world. Existing treatments for patients with HF are often associated with pro-arrhythmic activity and risk of sudden cardiac death. Therefore, development of novel, effective and safe therapeutic options for HF patients is a critical area of unmet need.

Areas covered: In this article, we review recent advances in the emerging field of cardiac gene therapy for the treatment of tachy- and bradyarrhythmias in HF. We provide an overview of gene-based approaches that modulate myocardial conduction, repolarization, calcium cycling and adrenergic signaling to restore heart rate and rhythm.

Expert opinion: We highlight major advantages of gene therapy for arrhythmias, including the ability to selectively target specific cell populations and to limit the therapeutic effect to the region that requires modification. We illustrate how advances in our fundamental understanding of the molecular origins of arrhythmogenic disorders are allowing investigators to use targeted gene-based approaches to successfully correct abnormal excitability in the atria, ventricles and conduction system. Translation of various gene therapy approaches to humans may revolutionize our ability to combat lethal arrhythmias in HF patients.     

Recent findings into the potential of gene therapy to reverse heart failure

The incidence of heart failure (HF) is ever growing and the mortality of HF patients is similar to patients suffering from cancer disease. The central clinical problem is a lack of therapies to target the underlying molecular defects that lead to chronic ventricular dysfunction. Substantial evidence points to a final common pathway in failing myocardium, including distinct changes in intracellular Ca²⁺-cycling and β-adrenergic receptor signaling. An attractive strategy to address these alterations is cardiac gene therapy and several distinct approaches have been undertaken during the last decade with impressing therapeutic benefit, at least in animal HF models. The present focus of research is the clinical translation of cardiac gene therapy including the optimization of vectors, delivery strategies and testing the compatibility with established pharmacologic treatment to improve the prognosis of HF in the near future.     

超声心动图预测慢性充血性心力衰竭患者心脏再同步化治疗急性反应

目的 探讨超声心动图预测慢性充血性心力衰竭(CHF)患者心脏再同步化治疗(CRT)急性反应的价值。方法 选取接受CRT的CHF患者33例,分别在CRT开启(ON)和关闭(OFF)状态下进行超声心动图检查,测量左心房最大前后径(LAD)、左心室舒张末内径(LVEDD)、左心室射血分数(LVEF)、房室同步性(A-V-D)、心室间同步性(V-V-D)。采用组织多普勒技术(TDI)测量左心室收缩(Vs-T-SD)和舒张同步性(Ve-T-SD);实时三维超声心动图(RT-3DE)检测左心室收缩同步性(T16-SD%)。将CRT-ON时,LVEF增加≥5%设为有反应(CRT-R)组,<5%为无反应(CRT-NR)组。对以上数据进行统计学分析。结果 25例患者(25/33,75.76%)为CRT-R组,8例(8/33,24.24%)为CRT-NR组。CRT-R组,CRT-ON时QRSd、LVEDD、LVESD、LAD、LVEDV、LVESV、V-V-D和T16-SD%较CRT-OFF时减小,LVSV和LVEF增加(P均<0.05);CRT-NR组,CRT-ON时LVEDD、LVESD和LAD较CRT-OFF时减小,LVEF增加(P均<0.05)。术前CRT-R组LAD和LVEDD小于CRT-NR组,而左束支传导阻滞和非缺血性心肌病患者的比例、V-V-D大于CRT-NR组(P均<0.05)。V-V-D为44 ms时,曲线下面积为0.747,预测CRT急性反应有效的敏感度及特异度分别为60.0%和87.5%(P<0.05)。结论 LAD和LVEDD较小、室间同步性较差且合并左束支传导阻滞的非缺血性心肌病的CHF患者更可能CRT急性反应有效,V-V-D可准确预测CRT急性反应。     

Relationship of baseline electrocardiographic characteristics with the response to cardiac resynchronization therapy for heart failure

Prospective identification of patients most and least likely to respond to cardiac resynchronization therapy (CRT) for congestive heart failure (CHF) will allow clinicians to target this intervention most efficiently. The authors hypothesized that ECG variables including RBBB and indicators of RV dysfunction and extensive prior myocardial infarction would correlate with diminished response to CRT. This study analyzed preimplantation ECGs in 110 patients with ICD indications and CHF due to left ventricular systolic dysfunction randomized to active biventricular pacing in the MIRACLE ICD trial. Clinical and ECG variables on the outcome of change in peak oxygen consumption from baseline to 6 months (Delta-VO2 ) were evaluated. For this cohort, average peak VO2 improved from 13.4 to 14.3 mL/kg per minute. Among clinical variables, the strongest predictors of increasing Delta-VO2 were reduced exercise time and peak VO2 at baseline. A dominant R wave in lead a VR, RBBB, and evidence of prior anterior infarction were each associated with significantly smaller average improvements in Delta-VO2 than their absence in univariate analysis. Alternative ECG criteria, including QRS duration, had no relationship with the outcome. In a multivariate model, only baseline VO2 (beta=-0.3, P=0.001) and ECG evidence of prior anterior infarction (beta=-1.3, P=0.03) were associated with the outcome. ECG markers of anterior infarction and RV dilation may help identify CHF patients unlikely to benefit from biventricular pacing. Further assessment is needed of these and other predictors of therapeutic response to CRT.     

Living with cardiac resynchronization therapy: Challenges for people with heart failure

The number of people with heart failure requiring implantation of a cardiac resynchronization device is increasing in Iran. Although this intervention is an effective life‐saving treatment, several challenges are associated with patients’ lifestyle after insertion. This study identified the challenges and coping mechanisms of Iranians with heart failure living with cardiac resynchronization therapy. A qualitative approach using conventional content analysis was adopted. Seventeen people with heart failure and three nurses were recruited between December 2014 and November 2015 from a teaching hospital and a private clinic in Rasht, Iran. Participants were interviewed using semi‐structured interviews lasting 30–60 min. Five themes emerged: (i) fear of implantation, (ii) the panic of receiving a shock from the device, (iii) lack of control over life, (iv) inadequacies of the healthcare system, and (v) psychosocial coping. A heightened understanding of these challenges and coping strategies could prepare healthcare professionals to provide better routine care, education, and support to the recipients of cardiac resynchronization therapy prior to implantation, during the recovery period, and for long‐term management.     

Pulmonary hypertension,heart failure and neutropenia due to diazoxide therapy

Primary persistent hyperinsulinaemic hypoglycaemia is characterised by clinical symptoms that occur when blood glucose levels drop below the normal range. Diazoxide treatment remains the mainstay of medical therapy. Tolerance of diazoxide is usually excellent, but several side effects of this drug have been described. We present a 4-month-old girl who developed pulmonary hypertension, heart failure and neutropenia during diazoxide therapy. Diazoxide toxicity was suspected and the drug was withdrawn on day 13. During the next 3 days, respiratory and haemodynamic status dramatically improved and she was weaned from mechanical ventilation. Control white blood cell count was 8800 cells/mm(3) and a new echocardiography showed modreduction of pulmonary artificial pressure to 20 mmHg and resolution of atrial and ventricular enlargement. Paediatric physicians should be in mind of pulmonary hypertension, heart failure and neutropenia developing during diazoxide therapy.     

Osteopathic manual therapy in heart failure patients: A randomized clinical trial

Background

Heart Failure (HF) patients usually present with increased arterial resistance and reduced blood pressure (BP) leading to an impaired functional capacity. Osteopathic Manual Therapy (OMT) focused on myofascial release techniques (MRT) and in the balancing of diaphragmatic tensions, has been shown to improve blood flow in individuals using the resistive index (RI). However, its effects in HF patients have not been examined.

QRS duration and shortening to predict clinical response to cardiac resynchronization therapy in patients with end-stage heart failure

Despite current selection criteria (NYHA Class III-IV, LVEF < 35%, QRS > 120 ms with LBBB), 30% of patients do not benefit from cardiac resynchronization therapy (CRT). The use of QRS duration as selection criteria for CRT has not been evaluated systematically yet. Accordingly, the value of QRS duration at baseline (and reduction in QRS duration after CRT) to predict responders was studied. Patients were evaluated at baseline and after 6 months of CRT for NYHA Class, quality of life score, and 6-minute walk test. QRS duration was evaluated before, directly after implantation, and after 6 months of CRT. Sixty-one patients were included; 45 (74%) patients were classified as responders (improvement of NYHA Class, 6-minute walking distance and quality of life score) and 16 (26%) as nonresponders. QRS duration at baseline was similar between the two groups: 179 +/- 30 ms versus 171 +/- 32 ms, NS. Directly after implantation, QRS duration was reduced from 179 +/- 30 ms to 150 +/- 26 ms (P < 0.01) in responders; nonresponders did not exhibit this reduction (171 +/- 32 ms vs 160 +/- 26 ms, NS). After 6 months of CRT, QRS shortening was only observed in responders (from 179 +/- 30 ms to 159 +/- 25 ms, P < 0.01). ROC curve analysis showed that a reduction in QRS duration > 10 ms had a high sensitivity (73%) with low specificity (44%); conversely, a > 50 ms reduction in QRS duration was highly specific (88%) but not sensitive (18%) to predict response to CRT. No optimal cutoff value could be defined. QRS duration at baseline is not predictive for response to CRT; responders exhibit a significant reduction in QRS duration after CRT, but individual response varies highly, not allowing adequate selection of responders.     

Cardiac resynchronization therapy in mildly symptomatic heart failure: the earlier the better

A new era is emerging in the field of complex pacing as a treatment for heart failure. Cardiac resynchronization therapy (CRT) is already established as an effective therapy to improve mortality and functional capacity in patients with moderate–severe heart failure, left ventricular systolic impairment and conduction delay (prolonged QRS duration on surface ECG). Recent evidence has demonstrated that CRT is also an effective treatment for patients with mild heart failure. As the indications for CRT expand, cardiologists face the exciting prospect of exploring where pacemaker technology can help improve patient outcomes across the entire heart failure disease continuum. Enthusiasm for future application needs to be tempered with the practicalities of delivering safe and effective care within the confines of finite healthcare resources.     

Is monocyte to HDL ratio superior to monocyte count in predicting the cardiovascular outcomes: evidence from a large cohort of Chinese patients undergoing coronary angiography

Aim: Recently, monocyte-to-high density lipoprotein ratio (MHR) has been proposed as a novel prognostic indicator of cardiovascular diseases. However, no study is currently available regarding the comparison between MHR and monocyte count (MC) in predicting the outcomes among patients undergoing coronary angiography.

Methods: A total of 3798 patients scheduled for selective coronary angiography were enrolled and followed up to capture major adverse cardiovascular events (MACEs, death, acute myocardial infarction, unstable angina, stroke, heart failure, and unexpected coronary revascularization). Cox proportional hazards models were used to evaluate the risk of MHR or MC on MACEs.

Results: During a median of 24.6 months follow-up, 347 (9.1%) MACEs occurred. The upper tertiles of MC and MHR have a significant lower event-free survival (p?=?0.011; p?=?0.014, respectively). Significantly, both MC and MHR were associated with increased MACEs risk after adjusting for potential confounders [adjusted HR (95% CI): 2.734 (1.547–4.832); 2.031 (1.268–3.254), respectively]. Additionally, the area under the receiver-operating characteristic curves of MC or MHR in predicting MACEs were 0.574 (0.542–0.606) and 0.562 (0.530–0.594) (p?Conclusions: Our data firstly indicated that MHR was an independent predictor of MACEs whereas the prognostic impact was not superior to MC in patients who underwent coronary angiography.

• Key Messages

• MHR has been suggested as a novel prognostic indicator of several cardiovascular diseases.

• No study is currently available regarding the comparison of MHR to MC in predicting the outcomes in a large cohort of patients undergoing coronary angiography.

• Our data firstly indicate that MHR is independently associated with MACEs in patients undergoing coronary angiography whereas the prognostic impact is similar to MC.

     

拓展式家庭系统治疗在慢性心力衰竭患者康复护理实践中的应用

目的：探讨拓展式家庭系统治疗在慢性心力衰竭患者康复护理实践中的应用效果。方法选取2015年1~9月收住我院的慢性心力衰竭患者99例为研究对象,随机分为对照组50例和实验组49例,对照组接受常规护理,实验组在对照组基础上接受拓展式家庭系统治疗,对两组干预后的各相关指标进行比较。结果实验组慢性心力衰竭患者干预后的家庭功能评分、生活质量评分均显著低于对照组,社会支持评分、自我护理行为评分均显著高于对照组,差异有统计学意义( P<0.05)。结论对慢性心力衰竭患者施以拓展式家庭系统治疗,对于提高其家庭功能、社会支持水平、自我护理行为能力和生活质量水平均具有积极的干预效果。     

Baroreflex activation therapy: a new treatment option for heart failure with reduced ejection fraction

Sympathovagal imbalance plays a major role in the progression of heart failure with reduced ejection fraction. Baroreflex activation therapy (BAT) by electrical stimulation of baroreceptors located at the carotid sinus can reduce sympathetic and increase parasympathetic tone. This review provides an overview on the concept of BAT in heart failure with reduced ejection fraction and available preclinical and clinical data. Animal studies of BAT in heart failure with reduced ejection fraction have demonstrated a decline in plasma norepinephrine, an improved left ventricular ejection fraction, a reduced susceptibility to induced ventricular arrhythmias and a survival benefit. First clinical data from uncontrolled studies suggest a relevant improvement in muscle sympathetic nerve activity, ejection fraction, 6-min walk distance, New York Heart Association (NYHA) class and hospitalization rate. BAT appears to be safe in this severely ill patient population.     

二维超声斑点追踪预测充血性心力衰竭患者心脏再同步化治疗的急性期反应

目的 观察二维超声斑点追踪(2D-STE)是否可预测充血性心力衰竭患者心脏再同步化治疗(CRT)的急性期反应.方法 24例充血性心力衰竭患者接受CRT治疗,术后7天分别在CRT关闭(OFF)和开启(ON)状态接受超声检查.将2D-STE测量的左心室短轴前间壁和后壁达峰值径向应变的时间差(T_(AS-POST))≥130 ms定义为左心室收缩不同步.将CRT-ON时左心室压力最大上升速率(LVdp/dt)的增长率Δdp/dt%>25%定义为急性反应有效.结果 15例患者(62.50%) CRT有反应,CRT-ON时左心室射血分数和LVdp/dt增大,T_(AS-POST) 缩短.T_(AS-POST) 是预测Δdp/dt%>25%的独立因素,T_(AS-POST)≥130 ms预测CRT急性反应的敏感度和特异度分别为86.24%和70.38%.结论 2D-STE技术能够有助于选择CRT最适病例,并预测其急性期反应.     

Cell and gene therapy for severe heart failure patients: The time and place for Pim-1 kinase

Regenerative therapy in severe heart failure patients presents a challenging set of circumstances including a damaged myocardial environment that accelerates senescence in myocytes and cardiac progenitor cells. Failing myocardium suffers from deterioration of contractile function coupled with impaired regenerative potential that drives the heart toward decompensation. Efficacious regenerative cell therapy for severe heart failure requires disruption of this vicious circle that can be accomplished by alteration of the compromised myocyte phenotype and rejuvenation of progenitor cells. This review focuses upon potential for Pim-1 kinase to mitigate chronic heart failure by improving myocyte quality through preservation of mitochondrial integrity, prevention of hypertrophy and inhibition of apoptosis. In addition, cardiac progenitors engineered with Pim-1 possess enhanced regenerative potential, making Pim-1 an important player in future treatment of severe heart failure.     

Cardiac resynchronization therapy: predictors of failure and strategies to overcome

Evaluation of: Macias A, Garcia-Bolao I, Diaz-Infante E et al. Cardiac resynchronization therapy: predictive factors of unsuccessful left ventricular lead implant. Eur. Heart J. 28, 450–456 (2007).

Congestive heart failure (CHF) is a leading cause of morbidity, mortality and hospitalization in the elderly of industrialized nations. In CHF patients with moderate-to-severe left ventricular systolic dysfunction and significant dyssynchrony, cardiac resynchronization therapy (CRT) has been shown to improve functional status and decrease heart failure mortality and hospitalizations. Inability to transvenously implant a lead within a desired branch of the coronary sinus for CRT occurs in 5–10% of cases. The article under evaluation identifies two independent predictors of failed transvenous left ventricular lead implantation – the presence of permanent atrial fibrillation and an increased anteroposterior left atrial diameter.     

HDL-replacement therapy: mechanism of action,types of agents and potential clinical indications

HDL-replacement therapy is a promising new treatment strategy involving the acute administration of HDL to rapidly stabilize patients at imminent risk for developing a myocardial infarction, such as those with acute coronary syndrome. This review will first focus on the anti-atherogenic mechanisms for HDL, such as the stimulation of the reverse cholesterol transport pathway, and then discuss the other potential beneficial biological effects of HDL on atherosclerosis. The various types of HDL-replacement therapies that are being investigated and developed will be reviewed and ongoing clinical trials and other possible clinical indications for HDL-replacement therapy besides the prevention of myocardial infarction will also be described. Finally, HDL-replacement therapy will be put into perspective by summarizing the current gaps in our knowledge of HDL metabolism and identifying challenges for future research in this area.     

Candesartan: from left ventricular hypertrophy to heart failure,a global approach

Cardiovascular disease is a continuum, starting with risk factors resulting from physiological changes and extending to vascular pathology associated with adverse clinical outcomes. The overactivation of the renin–angiotensin–aldosterone system has been related to the development and worsening of risk factors associated with cardiovascular diseases such as hypertension and heart failure. Treatment at each stage along the continuum may prevent, or at least delay, the next one, and so it is crucial to initiate therapy as early as possible in such patients so as to provide optimal care. Candesartan, a long-acting angiotensin receptor antagonist, has been shown to be an effective, and well-tolerated therapy, in both the early and late phases of cardiovascular disease (prehypertension, hypertension, left ventricular hypertrophy and heart failure). This article reviews the data supporting the use of candesartan in cardiovascular medicine, with a focus on left ventricular hypertrophy and ultimately heart failure. Particular emphasis is given to the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program, which has shown a positive impact of candesartan in patients with chronic heart failure in terms of reducing the incidence of cardiovascular deaths and chronic heart failure hospitalizations.     

Candesartan: from left ventricular hypertrophy to heart failure, a global approach

Cardiovascular disease is a continuum, starting with risk factors resulting from physiological changes and extending to vascular pathology associated with adverse clinical outcomes. The overactivation of the renin-angiotensin-aldosterone system has been related to the development and worsening of risk factors associated with cardiovascular diseases such as hypertension and heart failure. Treatment at each stage along the continuum may prevent, or at least delay, the next one, and so it is crucial to initiate therapy as early as possible in such patients so as to provide optimal care. Candesartan, a long-acting angiotensin receptor antagonist, has been shown to be an effective, and well-tolerated therapy, in both the early and late phases of cardiovascular disease (prehypertension, hypertension, left ventricular hypertrophy and heart failure). This article reviews the data supporting the use of candesartan in cardiovascular medicine, with a focus on left ventricular hypertrophy and ultimately heart failure. Particular emphasis is given to the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program, which has shown a positive impact of candesartan in patients with chronic heart failure in terms of reducing the incidence of cardiovascular deaths and chronic heart failure hospitalizations.     

Effectiveness of cognitive behavior therapy for patients with heart failure and depression: A systematic review protocol

The objective of this review is to determine the effectiveness of cognitive behavior therapy for patients with heart failure and depression, aged ≥18 years, in institutionalized healthcare settings. More specifically, the review aims to identify which cognitive behavior therapy strategy/strategies, including the method of delivery, is the most effective for the management of depression in hospitalized patients with heart failure. The review question is as follows: Is cognitive behavior therapy effective in reducing symptoms of depression in patients with heart failure? This systematic review will be conducted in accordance with the Joanna Briggs Institute methodology for systematic reviews of effectiveness evidence. This review only includes randomized controlled trials assessing the effectiveness of cognitive behavior therapy as a treatment for depression in adults (aged ≥18 years) with heart failure, compared with usual care, which might include medications.