Echo-driven V-V optimization determines clinical improvement in non responders to cardiac resynchronization treatment

Echocardiography plays an integral role in the detection of mechanical dyssynchrony in patients with congestive heart failure and in predicting beneficial response to cardiac resynchronization treatment. In patients who derive sup-optimal benefit from biventricular pacing, optimization of atrioventricular delay post cardiac resynchronization treatment has been shown to improve cardiac output. Some recent reports suggest that sequential ventricular pacing may further improve cardiac output. The mechanism whereby sequential ventricular pacing improves cardiac output is likely improved inter and possibly intraventricular synchrony, however these speculations have not been confirmed. In this report we describe the beneficial effect of sequential V-V pacing on inter and intraventricular synchrony, cardiac output and mitral regurgitation severity as the mechanisms whereby sequential biventricular pacing improves cardiac output and functional class in 8 patients who had derived no benefit or had deteriorated after CRT. Online tissue Doppler imaging including tissue velocity imaging, tissue synchronization imaging and strain and strain rate imaging were used in addition to conventional pulsed wave and color Doppler during sequential biventricular pacemaker programming.     

Pacing in congestive heart failure

Despite the major advances in medical drug therapy, heart failure remains a syndrome associated with high mortality and morbidity. Biventricular or left ventricular (LV) short atrioventricular (AV) delay pacing is being tested in congestive heart failure patients with left bundle branch block. The aim is to resynchronise the dyscoordinate LV contraction. A number of studies are underway, but it is clear that while some patients respond remarkably, this is highly variable. Accurate identification of patients likely to benefit will be crucial. The mechanism of benefit is unclear. A greater understanding of the physiological consequences of pacing will be necessary to accurately identify these patients.     

Biventricular stimulation therapy in patients with heart failure and tachycardic arrhythmias. Indications--results--prospects]

Biventricular pacing (BV-P) therapy is a new therapeutic approach in patients (pts) with drug refractory congestive heart failure; the beneficial effects of implantable cardioverter defibrillator (ICD) without BV-P therapy in patients (pts) with life-threatening ventricular tachyarrhythmias and impaired left ventricular (LV) function is associated with a relatively high cardiac and total mortality. We studied the follow-up of 410 pts (368 males, 42 females, mean age 57 +/- 11 years) after ICD implant. The LV function was assessed by the New York Heart functional class of heart failure (NYHA). Fifty pts (12%) were in NYHA I-II, 151 pts (37%) in NYHA II, 117 pts (29%) in NYHA II-III and 92 pts (22%) in NYHA III. Epicardial ICD implantation was performed in 209 pts (51%) and 201 pts (49%) received nonthoracotomy ICDs. Perioperatively (within 30 days after implant), 12 pts (3%) died, significantly more frequent after epicardial (11 of 209 pts, 5%) than after transvenous ICD implant (1 of 201 pts, < 1%)(p < 0.05). During a mean follow-up of 28 + 24 months (range < 1 to 114 months), 90 pts (23%) died: 9 pts (2%) died from sudden arrhythmic death and 5 pts (1%) suddenly, but probably not from arrhythmic causes; 55 pts (14%) died from cardiac causes (congestive heart failure, myocardial reinfarction) and 21 pts (5%) from noncardiac causes. 338 pts (82%) received ICD shocks (mean incidence 21 +/- 43 shocks per pt). Our data show that pts with LV dysfunction benefit from ICD therapy and that these pts survive for a considerable time after the first shock. However, survival is clearly influenced by the degree of left ventricular dysfunction and, in addition to ICD therapy, aggressive treatment of heart failure is necessary. Therefore, BV-P is a very promising concept to improve the worse prognosis in pts with moderate or severe congestive heart failure.     

The role of anemia in congestive heart failure and chronic kidney insufficiency: the cardio renal anemia syndrome

Anemia is a major problem in patients with chronic kidney insufficiency. The development of recombinant human erythropoietin has enabled physicians to correct this anemia. Although anemia has not been considered to be a common or important contributor to congestive heart failure, anemia of any cause can lead to cardiac damage and eventually congestive heart failure. Our joint renal-cardiac heart failure team found that anemia was indeed very common in congestive heart failure and was associated with severe, medication-resistant cardiac failure. Correction of the anemia with erythropoietin and intravenous iron led to a marked improvement in patients' functional status and their cardiac function, and to a marked fall in the need for hospitalization and for high-dose diuretics; renal function usually improved or at least stabilized. Subsequent investigations by others have confirmed many of our observations. We call this interrelationship between congestive heart failure, chronic kidney insufficiency, and anemia the Cardio-Renal Anemia syndrome. Treatment of the anemia in congestive heart failure may prove vital in preventing progression of both the heart failure and the associated renal disease.     

Importance of antioxidant and antiapoptotic effects of beta-receptor blockers in heart failure therapy

The present study was carried out to determine whether beneficial effects of carvedilol in congestive heart failure (CHF) are mediated via its beta-adrenergic blocking, antioxidant, and/or alpha-adrenergic blocking action. Rabbits with heart failure induced by rapid cardiac pacing were randomized to receive subcutaneous carvedilol, metoprolol, propranolol plus doxazosin, or placebo pellets for 8 wk and compared with sham-operated rabbits without pacing. We found rapid cardiac pacing produced clinical heart failure, left ventricular dilation, and decline of left ventricular fractional shortening. This was associated with an increase in left ventricular end-diastolic pressure, decrease in left ventricular first derivative of left ventricular pressure, and myocyte hypertrophy. Tissue oxidative stress measured by GSH/GSSG was increased in the heart with increased oxidation product of mitochondrial DNA, 8-oxo-7,8-dihydro-2'-deoxyguanosine, increase of Bax, decrease of Bcl-2, and increase of apoptotic myocytes as measured by anti-single-stranded DNA monoclonal antibody. Administration of carvedilol and metoprolol, which had no effect in sham animals, attenuated cardiac ventricular remodeling, cardiac hypertrophy, oxidative stress, and myocyte apoptosis in CHF. In contrast, propranolol plus doxazosin, which has less antioxidant effects, produced smaller effects on left ventricular function and myocyte apoptosis. In all animals, GSH/GSSG correlated significantly with changes of left ventricular end-diastolic dimension (r = -0.678, P < 0.0001), fractional shortening (r = 0.706, P < 0.0001), and apoptotic myocytes (r = -0.473, P = 0.0001). Thus our findings suggest antioxidant and antiapoptotic actions of carvedilol and metoprolol are important determinants of clinical beneficial effects of beta-receptors in the treatment of CHF.     

促红细胞生成素治疗慢性心力衰竭156例临床观察

目的:观察EPO对慢性充血性心力衰竭(CHF)治疗效果。方法:选择CHF患者212例,随机分为非EPO治疗组(56例)和EPO治疗组(156例)。其中非EPO治疗组采用常规抗心衰治疗,EPO治疗组接受常规抗心衰治疗和EPO治疗,直至临床观察结束。治疗后观察心功能指标改变。结果:156例心衰患者经过EPO治疗后,左室射血分数,每搏输出量,每分输出量,心指数均较非EPO治疗对照组患者明显改善(P<0.05),其中尤以左室射血分数改善最为明显(P<0.01)。156例EPO治疗组患者中116例心衰伴贫血患者心功能各项指标的改善较40例心衰不伴贫血患者更为明显,具有显著统计学意义(P<0.01)。结论:EPO对CHF患者心功能的改善主要是因为EPO的促红细胞生成作用。EPO对于慢性心功能不全有独立于促红细胞生成以外的治疗作用。     

Système pour la stimulation cardiaque du ventricule gauche sur de multiples électrodes reconfigurables avec une électronique encapsulée hermétique et biocompatible

MULTICARDE is a Tecsan ANR exploratory project that was launched in 2007 and ended up in 2009. ELA Medical (SORIN Group) and the CEA-Leti were associated for this development. The project aims at enhancing the therapy for congestive heart failure based on biventricular electrical resynchronization therapy. Several studies proved the efficiency of this therapy, which remains subjected to the good positioning of the left pacing lead. The MULTICARDE project develops a programmable multi-electrodes pacing to improve the hemodynamic status of the patient. Multiple constraints must be taken into account for this kind of project, such as the power consumption, the size and the interoperability towards leads’ standards. To address these requirements an innovative collective packaging process was developed to integrate electronics inside the lead.     

Statement of the ad hoc committee on the laboratory diagnosis of infectious and serum hepatitis.

A prospective study was carried out to determine the prognostic factors in patients with second-degree and complete heart block following acute myocardial infarction and to re-examine the indications for artificial transvenous pacing. Of the 117 consecutive patients with proved acute myocardial infarction, 15 developed advanced heart block (second degree and complete). The presence of the following factors, either alone or in combinations, were attended with poor prognosis: preceding Stokes-Adams syndrome, cardiogenic shock, congestive heart failure, complications secondary to cardiac arrest, anterior infarction and wide QRS complex. In the nine cases requiring artificial transvenous pacemaker because of Stokes-Adams attacks, congestive heart failure or frequent multifocal ventricular ectopic beats, there were five deaths. The remaining six patients, who were without complications and were not paced, all survived; these patients had normal QRS duration with heart rates above 60 per minute. This study indicates that prophylactic transvenous catheter insertion in acute heart block does not appear justified unless specific indication(s) arise. Postmortem studies revealed significant narrowing of all the major coronary vessels in all five fatalities. The overall mortality in this series of cases of acute heart block was 33%.     

心室不同部位起搏对正常犬和扩张型心肌病心力衰竭犬模型在体心肌跨室壁复极离散的影响

实验以正常犬和扩张型心肌病心力衰竭犬(dilated cardiomyopathy congestive heart failure,DCM-CHF)模型为对象、以心肌跨室壁复极离散的相关参数为指标,研究左心室心外膜起搏、双心室起搏(模拟临床上心室再同步治疗的方法)后的心肌电生理特性变化。实验以快速右心室起搏的方法制备DCM-CHF犬模型;正常犬和DCM-CHF犬均经射频消融希氏束制备三度房室传导阻滞模型;采用同步记录犬体表心电图和内膜下、中层、外膜下三层心肌单相动作电位(monophasic action potentials,MAP)的方法,测定不同部位起搏时的QT间期、Tpeak-Tend(Tp-Te)间期和三层心肌的单相动作电位时程(MAP duration,MAPD)、跨室壁复极离散度(transmural dispersion of repolaization,TDR)。结果显示:在正常犬,左室心外膜与双心室起搏后三层心肌的MAPD均延长,同时TDR增大(左室心外膜起搏47.16 ms、双心室起搏37.54 ms、右室心内膜起搏26.75 ms,P<0.001),体表心电图Tp-Te间期的变化与之平行;在DCM-CHF犬较正常犬已表现出中层心肌MAPD延长(276.30 ms vs 257.35 ms,P<0.0001)和TDR(33.8 ms vs 27.58 ms,P=0.002)增大的基础上,左室心外膜参与起搏后仍进一步使三层心肌的MAPD延长和TDR增大。研究结果提示,左室心外膜起搏和双心室起搏后使内膜下、中层     

Mechanical circulatory support

Currently, almost five million Americans and 23 million people worldwide are living with congestive heart failure (CHF), with 2 million new cases diagnosed each year. The etiology is mostly ischemic, idiopathic, or viral, and more than $36 billion is spent each year on the care of congestive heart failure patients. Treatment of advanced CHF takes three forms: medical therapy, surgical therapy and cardiac replacement. Medical therapy, including inotropes and vasodilators, relieves symptoms by reducing cardiac work and increasing myocardial contractility. This has helped improve quality of life, but mortality remains unaffected. Surgical therapy, including revascularization, ventricular restoration and valve replacement/repair, relieves symptoms and improves function, but in most cases does not stop the underlying disease process from progressing. When conventional medical or surgical therapies are exhausted, cardiac assist or replacement, including ventricular assist device (VAD), heart transplant or a total artificial heart (TAH) may become the only therapeutic options. This article will not discuss the use of extracorporeal membrane oxygenation for cardiac support that is described in an additional article in this issue of Organogenesis.     

Left ventricular pacing in patients with congestive heart failure

Cardiac resynchronisation therapy (CRT) using biventricular (BIV) pacing has proved its effectiveness to correct myocardial asynchrony and improve clinical status of patients with severe congestive heart failure (CHF) and widened QRS. Despite a different effect on left ventricular electrical dispersion, left univentricular (LV) pacing is able to achieve the same mechanical synchronisation as BIV pacing in experimental studies and in humans. This results in clinical benefits of LV pacing at mid-term follow-up, with significant improvement in functional class, quality of life and exercise tolerance at the same extent as those observed with BIV stimulation in non randomised studies. Furthermore these benefits are obtained at lesser costs and with conventional dual-chamber devices. However, LV pacing has to be compared to BIV pacing in randomised trials before being definitely considered as a cost-effective alternative to BIV pacing.     

Cheyne-Stokes respiration in congestive heart failure.

Cheyne-Stokes respiration is an abnormal breathing pattern which commonly occurs in patients with decompensated congestive heart failure and neurologic diseases, in whom periods of tachypnea and hyperpnea alternate with periods of apnea. In the majority of these patients, the ventilatory patterns may not be recognized, and the clinical features are generally dominated by the underlying disease process. Cheyne-Stokes respiration may, however, have profound effects on the cardiopulmonary system, causing oxygen desaturation, cardiac arrhythmias, and changes in mental status. Treatment of Cheyne-Stokes respiration in congestive heart failure with supplemental oxygen or nasal continuous positive airway pressure, in addition to conventional therapy, may improve the overall cardiac function and perhaps the patient's prognosis.     

The effects of right ventricular apical pacing on left ventricular function. Stimulation of the right ventricular apex: should it still be the gold standard?

Current pacing practice is undergoing continuous and substantial changes. Initially pacing had an exclusively palliative role, since it was reserved for patients developing complete heart block or severe symptomatic bradycardia. With the appearance of novel pacing indications such as pacing for heart failure and atrial fibrillation, the effect of pacing site on cardiac function has become a critically important issue and a subject for consideration. It seems that the classical pacing site in the right ventricular apex is no longer the gold standard because of possible disadvantageous effects on cardiac function. The aim of this review article is to discuss the effect of right ventricular apical pacing on cardiac function including cellular and hemodynamic changes. We also aim to discuss the role of alternative pacing sites in the light of cardiac function.     

Cardiomyocyte proliferation,a target for cardiac regeneration

Cardiac diseases, characterized by cardiomyocyte loss, lead to dramatic impairment of cardiac function and ultimately to congestive heart failure. Despite significant advances, conventional treatments do not correct the defects in cardiac muscle cell numbers and the prognosis of congestive heart failure remains poor. The existence, in adult mammalian heart, of low but detectable cardiomyocyte proliferative capacities has shifted the target of regenerative therapy toward new therapeutical strategy. Indeed, the stimulation of terminally differentiated cardiomyocyte proliferation represents the main therapeutic approach for heart regeneration. Increasing evidence demonstrating that the loss of mammalian cardiomyocyte renewal potential shortly after birth causes the loss of regenerative capacities, strongly support the hypothesis that a detailed understanding of the molecular mechanisms controlling fetal and postnatal cardiomyocyte proliferation is essential to identify targets for cardiac regeneration. Here, we will review major developmental mechanisms regulating fetal cardiomyocyte proliferation and will describe the impact of the developmental switch, operating at birth and driving postnatal heart maturation, on the regulation of adult cardiomyocyte proliferation, all these mechanisms representing potential targets for cardiac repair and regeneration.     

Coupled pacing improves cardiac efficiency during acute atrial fibrillation with or without cardiac dysfunction

Coupled pacing (CP), a method for controlling ventricular rate during atrial fibrillation (AF), consists of a single electrical stimulation applied to the ventricles after each spontaneous activation. CP results in a mechanical contraction rate approximately one-half the rate during AF. Paired stimulation in which two electrical stimuli are delivered to the ventricles has also been proposed as a therapy for heart failure. Although paired stimulation enhances contractility, it greatly increases energy consumption. The primary hypothesis of the present study is that CP improves cardiac function during acute AF without a similar increase in energy consumption because of the reduced rate of ventricular contractions. In a canine model, CP was applied during four stages: sinus rhythm (SR), acute AF, cardiac dysfunction (CD), and AF in the presence of cardiac dysfunction. The rate of ventricular contraction decreased in all four stages as the result of CP. In addition, we determined the changes in external cardiac work, myocardial oxygen consumption, and myocardial efficiency in the each of four stages. CP partially reversed the effects of AF and CD on external cardiac work, whereas myocardial oxygen consumption increased only moderately. In all stages but SR, CP increased myocardial efficiency because of the marked increases in cardiac work compared with the moderate increases in total energy consumed. Thus this pacing therapy may be a viable therapy for patients with concurrent atrial fibrillation and heart failure.     

Plasma glucose, insulin and free fatty acids in infants with congenital heart disease.

The effect of congestive cardiac failure, hypoxia and hypoglycaemia on glucose tolerance and insulin secretion were studied in selected groups of infants with congenital heart disease. Fasting blood glucose level was significantly decreased in patients with congestive heart failure and in cyanotic infants without congestive heart failure. In the former it seemed to be correlated with the degree of malnutrition, while in cyanotic infants it was independent of the nutritional state. Plasma insulin levels were reduced in infants, with congestive cardiac failure, although their glucose tolerance test and free fatty acid concentrations were normal. It is suggested that the decreased plasma insulin concentration was a consequence of adaptation to reduced requirements. Glucose tolerance and insulin secretion were not affected by hypoxia or hypoglycaemia.     

Haemodynamic Studies with Peruvoside in Human Congestive Heart Failure

The immediate haemodynamic effects of peruvoside, a cardiac glycoside obtained from the Indian plant Thevetia neriifolia Juss, were studied in six patients with congestive heart failure. The drug was found to have an immediate and powerful positive inotropic and negative chronotropic effect, like ouabain, on the failing human heart. Oral peruvoside was also effective in the treatment of congestive heart failure when used on a short-term as well as a long-term basis. It therefore seems that peruvoside is a useful cardiac glycoside in the management of congestive heart failure in man as a quick-acting intravenous preparation. It is equally effective when used orally.     

Adverse effects of atrioventricular synchronous right ventricular pacing on left ventricular sympathetic activity, efficiency, and hemodynamic status

Right ventricular (RV) pacing is now recognized to play a role in the development of heart failure in patients with and without underlying left ventricular (LV) dysfunction. We used the cardiac norepinephrine spillover method to test the hypothesis that RV pacing is associated with cardiac sympathetic activation. We studied 8 patients with normal LV function using temporary right atrial and ventricular pacing wires. All measurements were carried out during a fixed atrial pacing rate. The radiotracer norepinephrine spillover technique was employed to measure total body and cardiac sympathetic activity while changes in LV performance were evaluated with a high-fidelity manometer catheter. Atrioventricular synchronous RV pacing, compared with atrial pacing alone, was associated with a 65% increase in cardiac norepinephrine spillover, an increase in LV end-diastolic pressure, and a reduction in myocardial efficiency. These responses may play a role in the development of heart failure and poor outcomes that are associated with chronic RV pacing.     

Metabolic modulation and cellular therapy of cardiac dysfunction and failure

At present the prevalence of heart failure rises along with aging of the population. Current heart failure therapeutic options are directed towards disease prevention via neurohormonal antagonism (β-blockers, angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers and aldosterone antagonists), symptomatic treatment with diuretics and digitalis and use of biventricular pacing and defibrillators in a special subset of patients. Despite these therapies and device interventions heart failure remains a progressive disease with high mortality and morbidity rates. The number of patients who survive to develop advanced heart failure is increasing. These patients require new therapeutic strategies. In this review two of emerging therapies in the treatment of heart failure are discussed: metabolic modulation and cellular therapy. Metabolic modulation aims to optimize the myocardial energy utilization via shifting the substrate utilization from free fatty acids to glucose. Cellular therapy on the other hand has the goal to achieve true cardiac regeneration. We review the experimental data that support these strategies as well as the available pharmacological agents for metabolic modulation and clinical application of cellular therapy.     

两种心衰模型大鼠心功能的比较

目的　比较两种心衰模型大鼠心功能的特点。方法　用腹主动脉、下腔静脉穿刺造瘘法及冠脉结扎法建立不同的心衰模型 ,用Doppler超声心动图及心脏称重的方法比较其心功能的各项参数。结果　两组大鼠的相对心脏重量均有所增高。造瘘组射血分数有所下降 ,但心输出量、血压维持正常 ,而冠脉结扎组术后 3周射血分散、心输出量和平均动脉压均明显下降 ,等容舒张期延长。结论　腹主动脉、下腔静脉穿刺造瘘所造成的是高输出量心衰 ,而冠脉结扎法所造成的是低输出量心衰 ,其心衰程度更为严重。Doppler超声心动图为大鼠心功能的检测提供了一种简单、可靠、可随访的无创伤性检查方法。