Maze procedure in patients with left ventricular dysfunction

Background

The risks and benefits of a concomitant Maze procedure for patients with LV dysfunction undergoing major cardiac surgery have not yet been elucidated. This study aimed to evaluate the clinical impacts of the Maze procedure in patients with atrial fibrillation and left ventricular (LV) dysfunction.

Methods

Between January 1999 and March 2011, a total of 139 patients (mean age 52.7 ± 12.3 years, 54 females) with valvular atrial fibrillation (AF) and an LV ejection fraction (EF) of 40% or less underwent open heart surgery with (n = 77) or without (n = 62) a concomitant Maze procedure. We compared adverse outcomes (death and composite of death, thromboembolic events and congestive heart failure [CHF]) during a median follow-up period of 66.0 months (inter-quartile range, 27.5–106.9 months).

Results

Adverse events occurred in 41 patients, including 36 deaths, seven thromboembolic events and eight hospitalizations due to CHF. After adjustment for baseline profiles with the use of propensity scores and inverse probability weighting, patients who had the Maze procedure were at lower risks of death (hazard ratio, 0.39; 95% confidence interval, 0.16–0.93; P = 0.033) and composite adverse outcomes (hazard ratio, 0.28; 95% confidence interval, 0.14–0.57; P = 0.017) than those not undergoing the Maze procedure. Furthermore, the Maze procedure resulted in superior functional status (P < 0.001) and reduced the need for long-term anticoagulation therapy (67.1% vs. 91.2%, P = 0.001).

Conclusion

Performing the Maze procedure on patients with valvular AF and LV dysfunction reduced serious adverse outcomes and the need for long-term anticoagulation therapy when compared to cardiac surgery alone without the Maze procedure.     

Hypertonic saline with furosemide for the treatment of acute congestive heart failure: A systematic review and meta-analysis

Background

Advanced congestive heart failure (CHF) therapies include intravenous inotropic agents, change in class of diuretics, and venous ultrafiltration or hemodialysis. These modalities have not been associated with improved prognosis and are limited by availability and cost. Compared to high-dose furosemide alone, concomitant hypertonic saline solution (HSS) administration has demonstrated improved clinical outcomes with good safety profile.

Methods

A literature search was conducted for randomized controlled trials that investigated the use of HSS in patients admitted to hospital with acute CHF.

Results

1032 patients treated with HSS and 1032 controls, demonstrated decreased all-cause mortality in patients treat with HSS with RR of 0.56 (95% CI 0.41–0.76,p = 0.0003). 1012 patients treated with HSS and 1020 controls, demonstrated decreased heart failure hospital readmission with RR of 0.50 (95% CI 0.33–0.76,p = 0.001). Patients treated with HSS also demonstrated decreased hospital length of stay (p = 0.0002), greater weight loss (p < 0.00001), and preservation of renal function (p < 0.00001).

Conclusion

The results of this meta-analysis demonstrate that in patients with advanced CHF concomitant hypertonic saline administration improved weight loss, preserved renal function, and decreased length of hospitalization, mortality and heart failure rehospitalization. A future adequately powered, multi-centre, placebo controlled, randomized, double dummy, blinded trial is needed to assess the benefit of hypertonic saline in patients with renal dysfunction, in diverse patient populations, as well using a patient population on optimal current heart failure treatment. Pending further validation, there is promise for hypertonic saline as an advanced therapy for the management of acute advanced CHF.     

Anti-obesity effects of KR-66195, a synthetic DPP-IV inhibitor,in diet-induced obese mice and obese-diabetic ob/ob mice

Objective

We investigated whether KR-66195, a new synthetic dipeptidyl dipeptidase IV inhibitor, could prevent weight gain, as well as improving glycemic control in diet-induced obese (DIO) and ob/ob mice.

Materials/Methods

Male C57BL/6 mice were randomly assigned to the following groups: chow diet, high-fat diet, and high-fat diet with KR-66195. After KR-66195 treatment for eight weeks, intraperitoneal glucose tolerance tests were performed. A pair-feeding study was performed to investigate the mechanisms of the anti-obesity effects of KR-66195 in DIO mice. Female ob/ob mice were treated with KR-66195 for three weeks and compared to the vehicle-treated group.

Results

In DIO mice, KR-66195 treatment increased the plasma glucagon-like peptide (GLP)-1 levels and improved glucose tolerance. This treatment also reduced body weight gain (5.38 ± 0.94 g vs. 12.08 ± 0.55 g, P < 0.01) and food intake (2.41 ± 0.09 g vs. 2.79 ± 0.11 g, P < 0.05). In ob/ob mice, KR-66195 treatment for three weeks resulted in comparable effects in DIO mice. In the pair-feeding study, KR-66195-treated mice exhibited a 16% increase in energy expenditure (kcal/h/kg lean body mass) without significant differences in body weight or activities compared with pair-fed mice. These results suggest that KR-66195 prevented weight gain in DIO mice by decreasing food intake, as well as increasing energy expenditure.

Conclusions

KR-66195 markedly increased plasma levels of GLP-1, resulting in the probable improvement in glucose tolerance and reduced body weight and food intake. Thus, KR-66195 might be further developed as a therapeutic drug to treat obesity, as well as diabetes.     

Left ventricular diastolic function in relation to the urinary proteome: A proof-of-concept study in a general population

Background

In previous studies, we identified two urinary proteomic classifiers, termed HF1 and HF2, which discriminated subclinical diastolic left ventricular (LV) dysfunction from normal. HF1 and HF2 combine information from 85 and 671 urinary peptides, mainly up- or down-regulated collagen fragments. We sought to validate these classifiers in a population study.

Methods

In 745 people randomly recruited from a Flemish population (49.8 years; 51.3% women), we measured early and late diastolic peak velocities of mitral inflow (E and A) and mitral annular velocities (e' and a') by conventional and tissue Doppler echocardiography, and the urinary proteome by capillary electrophoresis coupled with mass spectrometry.

Results

In the analyses adjusted for sex, age, body mass index, blood pressure, heart rate, LV mass index and intake of medications, we expressed effect sizes per 1-SD increment in the classifiers. HF1 was associated with 0.204 cm/s lower e' peak velocity (95% confidence interval, 0.057–0.351; p = 0.007) and 0.145 higher E/e' ratio (0.023–0.268; p = 0.020), while HF2 was associated with a 0.174 higher E/e' ratio (0.046–0.302; p = 0.008). According to published definitions, 67 (9.0%) participants had impaired LV relaxation and 96 (12.9%) had elevated LV filling pressure. The odds of impaired relaxation associated with HF1 was 1.38 (1.01–1.88; p = 0.043) and that of increased LV filling pressure associated with HF2 was 1.38 (1.00–1.90; p = 0.052).

Conclusions

In a general population, the urinary proteome correlated with diastolic LV dysfunction, proving its utility for early diagnosis of this condition.     

Ghrelin and cannabinoids require the ghrelin receptor to affect cellular energy metabolism

Introduction

Ghrelin is a potent orexigenic brain-gut peptide with lipogenic and diabetogenic effects, possibly mediated by growth hormone secretagogue receptor (GHS-R1a). Cannabinoids also have orexigenic and lipogenic effects. AMPK is a regulator of energy homeostasis and we have previously shown that ghrelin and cannabinoids stimulate hypothalamic AMPK activity while inhibiting it in the liver and adipose tissue, suggesting that AMPK mediates both the central appetite-inducing and peripheral effects of ghrelin and cannabinoids.

Aims

Using GHS-R KO mice, we investigated whether the known ghrelin receptor GHS-R1a is required for the tissue-specific effects of ghrelin on AMPK activity, and if an intact ghrelin signalling pathway is necessary for the effects of cannabinoids on AMPK activity.

Methods

Wild-type and GHS-R KO mice were treated intraperitoneally with ghrelin 500 ng/g bodyweight or CB1 agonist HU210 20 ng/g and hypothalamic, hepatic and adipose AMPK activity was studied using a functional kinase assay.

Results

Ghrelin and HU210 significantly stimulated hypothalamic AMPK activity in wild-type animals (mean ± SEM, 122.5 ± 5.2% and 128 ± 11.6% of control, p < 0.05) and inhibited it in liver (55.1 ± 4.8% and 62.2 ± 14.5%, p < 0.01) and visceral fat (mesenteric fat (MF): 54.6 ± 16% and 52.0 ± 9.3%, p < 0.05; epididymal fat (EF): 47.9 ± 12.1% and 45.6 ± 1.7%, p < 0.05). The effects of ghrelin, and interestingly also HU210, on hypothalamic, visceral fat and liver AMPK activity were abolished in the GHS-R KO mice (hypothalamus: 107.9 ± 7.7% and 87.4 ± 13.3%, liver: 100.5 ± 11.6% and 116.7 ± 5.4%, MF: 132.1 ± 29.9% and 107.1 ± 32.7%, EF: 89.8 ± 7.3% and 91.7 ± 18.3%, p > 0.05).

Conclusions

Ghrelin requires GHS-R1a for its effect on hypothalamic, liver and adipose tissue AMPK activity. An intact ghrelin signalling pathway is necessary for the effects of cannabinoids on AMPK activity.     

Transient variations of transthoracic impedance as a predictor of heart failure and death in patients with implanted defibrillators

Background

Transient variations in physiological parameters may forewarn of life-threatening cardiac events, but are difficult to identify clinically. Implantable cardioverter defibrillators (ICD) designed to measure transthoracic impedance provide a surrogate marker for pulmonary congestion.

Objective

The aim of this study is to determine if the frequency of changes in transthoracic impedance (TTI) is associated with congestive heart failure (CHF) exacerbation and predicts mortality.

Methods

We followed 109 consecutive patients (pts) with ICDs (n = 58) or CRT-ICDs (n = 51) for a mean of 21.3 (+ 10.2) months. Using 80 ohm-days as a reference, we correlated the frequency of TTI changes above this index to CHF hospitalizations or death.

Results

There was at least one TTI threshold crossing in 79 (72%) pts over 23.3 months follow-up, with a mean of 1.8 ± 3.4 per year. There were 18 pts with CHF hospitalizations who had a mean of 4.3 TTI threshold crossings/year (S.D. = ± 7.3; median = 2.8), compared to 1.3 (S.D. = ± 1.5; median = 0.8) among pts without CHF hospitalizations (p = 0.0006). Among 20 patients who died during follow-up, there were 4.2 (S.D. = ± 7.0; median = 2.9) TTI threshold crossings/year, compared with 1.3 (S.D. = ± 1.3; median = 0.9) threshold crossings/year among survivors (p = 0.0004). Using Cox Proportional Hazard modeling, after adjusting for age, baseline EF, and number of shocks, TTI threshold crossing was an independent predictor of death (HR 1.72, 95% CI 1.26–2.36, p = 0.001).

Conclusions

Increased frequency of TTI threshold crossings may be a useful predictor of transient risk for identifying a subgroup of ICD recipients at greater individual risk for death or CHF hospitalizations.     

Effective sleep apnoea treatment improves cardiac function in patients with chronic heart failure

Background

Sleep disordered breathing (SDB) is highly prevalent in patients with chronic heart failure (CHF) and is associated with adverse effects on cardiac geometry and function. Continuous positive airway pressure (CPAP) has been proved an effective treatment modality for obstructive sleep apnoea (OSA), whereas adaptive servoventilation (ASV) is more effective in patients with central sleep apnoea (CSA). The impact of selection of therapy and effective apnoea alleviation on cardiac performance and reverse left ventricular remodelling (r-LVR) has not yet been evaluated.

Methods

Eighty five patients with stable CHF were screened for SDB and underwent polysomnography and treatment according to the type of SDB. Clinical evaluation and a comprehensive echocardiographic study was performed before initiation of therapy and after six months of effective treatment (ventilator use > 5 h/day with AHI < 5 events/h).

Results

Seventeen compliant patients under effective treatment were included in the analysis (8 OSA under Autoset CPAP and 9 CSA under ASV). In both groups, a significant improvement in all measured, conventional and TDI LV systolic indexes was recorded, including LVEF (32% ± 6% vs. 27% ± 6%, p < 0.001). A decrease in LV end-systolic volume (189 ± 94 ml vs. 211 ± 88 ml, p = 0.015, difference > 10%) was indicative of r-LVR. Furthermore, RV systolic parameters were also increased (TAPSE, p < 0.001; systolic TDI wave from lateral tricuspid annular aspect, p = 0.001), whereas right heart dimensions and areas were diminished, indicating better pulmonary haemodynamics. Moreover, a significant improvement in patients' clinical status, as evaluated by New York Heart Association Class was also documented at the end of six months follow-up.

Conclusions

Effective alleviation of SDB in CHF patients is associated with significant improvements in LV and RV systolic function and r-LVR. Longitudinal studies are needed to evaluate effects on morbidity and mortality.     

Cardiorenal anemia syndrome in chronic heart failure contributes to increased sympathetic nerve activity

Background

We sought to assess whether cardiorenal anemia syndrome (CRAS) in chronic heart failure (CHF) patients contributes to sympathetic overactivity through modulation of sympathetic reflexes.

Methods and results

We prospectively studied 15 patients with CRAS and CHF and 15 control CHF patients, matched for age, gender distribution, type of cardiomyopathy, left ventricular ejection fraction (LVEF) and BMI. We compared muscle sympathetic nerve activity (MSNA) and the effect of peripheral chemoreflex deactivation on MSNA in both groups. We also compared sympathetic baroreflex function, assessed by the slope of the relationship between MSNA and diastolic blood pressure in both groups and while peripheral chemoreflexes were (by breathing 100% oxygen for 15 min) or not deactivated. Baseline MSNA was significantly elevated in CHF patients with CRAS compared with control CHF patients (83.1 ± 4.6 versus 64.9 ± 2.9 bursts/100 heart beats; P < 0.05) and sympathetic baroreflex impaired (2.69 ± 0.44 vs 5.25 ± 0.60% bursts/mm Hg; P < 0.01). Chemoreflex deactivation with administration of 100% oxygen led to a significant decrease in muscle sympathetic nerve activity (77.8 ± 4.7 versus 82.1 ± 4.9 bursts/100 heart beats; P < 0.01) and to an increase in sympathetic baroreflex function (2.77 ± 0.45 vs 5.63 ± 0.73% bursts/mm Hg; P < 0.01) in patients with CRAS and CHF. In contrast, neither room air nor 100% oxygen changed MSNA, hemodynamic or sympathetic baroreflex function in control CHF patients.

Conclusions

CRAS in CHF patients is associated with elevated sympathetic activity mediated by both tonic activation of peripheral chemoreflex and baroreflex impairment.     

Tele-accelerometry as a novel technique for assessing functional status in patients with heart failure: Feasibility,reliability and patient safety

Background

The six-minute walk test (6MWT) is an established measure of functional exercise capacity associated with clinical prognosis in Chronic Heart Failure (CHF). The aim of this study is to evaluate the employment of tele-accelerometry for the remote assessment of 6MWT in CHF.

Methods

155 patients were subjected to tele-accelerometry in form of monthly 6MWTs in their home surroundings. Accelerometer output included steps/6 min and walking speed. Data was directly transferred via mobile network to the Telemedicine Centre subsequent to test completion. 6MWT distance was measured by hand wheel and steps were counted with a digital hand-counter at baseline (Test 1) and at 12 months follow-up (Test 2).

Results

Accelerometer accuracy was within the 99th percentile. There was a significant correlation between step count, walking speed and measured 6MWT distance (Test 1: steps: r = 0.80, P < 0.001; Test 2: steps: r = 0.90, P < 0.001 and Walking Speed Test 1: r = 0.80, P < 0.001; Walking Speed Test 2: r = 0.86, P < 0.001). The reproducibility of tele-accelerometry was within 95% margin for all performance parameters, which showed stronger associations to quality of life questionnaire (Short Form - 36) Physical Component Score (PCS) than New York Heart Association (NYHA) functional class.

Conclusion

Tele-accelerometry is feasible in patients with CHF and output parameters are indicative of exercise capacity. The benefit of this approach lies in its simplicity under every day circumstances by enabling routine performance testing to assess patients' functional status.     

Central and peripheral quadriceps fatigue in congestive heart failure

Aims

The clinical syndrome of heart failure includes exercise limitation that is not directly linked to measures of cardiac function. Quadriceps fatigability may be an important component of this and this may arise from peripheral or central factors.

Methods and results

We studied 10 men with CHF and 10 healthy age-matched controls. Compared with a rest condition, 10 min after incremental maximal cycle exercise, twitch quadriceps force in response to supramaximal magnetic femoral nerve stimulation fell in both groups (CHF 14.1% ± 18.1%, p = 0.037; Control: 20.8 ± 11.0%, p < 0.001; no significant difference between groups). There was no significant change in quadriceps maximum voluntary contraction voluntary force. The difference in the motor evoked potential (MEP) response to transcranial magnetic stimulation of the motor cortex between rest and exercise conditions at 10 min, normalised to the peripheral action potential, also fell significantly in both groups (CHF: 27.3 ± 38.7%, p = 0.037; Control: 41.1 ± 47.7%, p = 0.024). However, the fall in MEP was sustained for a longer period in controls than in patients (p = 0.048).

Conclusions

The quadriceps is more susceptible to fatigue, with a similar fall in TwQ occurring in CHF patients at lower levels of exercise. This is associated with no change in voluntary activation but a lesser degree of depression of quadriceps motor evoked potential.     

Coronary artery bypass grafting in patients with left ventricular dysfunction: Predictors of long-term survival and impact of surgical strategies

Background

In the surgical management of ischemic cardiomyopathy, factors associated with long-term prognosis after coronary artery bypass grafting (CABG) in patients with severe left ventricular (LV) dysfunction are poorly understood. This study aimed to determine predictors of clinical outcomes in patients with severe LV dysfunction undergoing CABG.

Methods

Out of 6084 patients who underwent CABG between 1997 and 2011, 476 patients (aged 62.6 ± 9.3 years, 100 females) were identified as having severe LV dysfunction (ejection fraction ≤ 35%), preoperatively. All-cause mortality and adverse cardiac events (myocardial infarction, repeat revascularization, stroke and hospitalization due to cardiovascular causes) were evaluated during a median follow-up period of 55.2 months (inter-quartile range: 26.4–94.8 months).

Results

During the follow-up, 187 patients (39.3%) died and 126 cardiac events occurred in 104 patients (21.8%). Five-year survival and event-free survival rates were 72.1 ± 2.2% and 61.3 ± 2.4%, respectively. On Cox-regression analysis, old age (P < 0.001), recent MI (P < 0.001), history of coronary stenting (P = 0.023), decreased glomerular filtration rate (P < 0.001), and presence of mitral regurgitation (≥ moderate) (P = 0.012) or LV wall thinning (P = 0.007) emerged as significant and independent predictors of death. After adjustment for important covariates affecting outcomes, none of the pump strategy (off-pump vs. on-pump), concomitant mitral surgery or surgical ventricular reconstruction (SVR) affected survival or event-free survival (P = 0.082 to > 0.99).

Conclusions

Long-term survival following CABG in patients with severe LV dysfunction was affected by age, renal function, recent MI, prior coronary stenting, and presence of mitral regurgitation or LV wall thinning. Neither concomitant mitral surgery nor SVR, however, had significant influence on clinical outcomes.     

Medical therapy versus implantable cardioverter -defibrillator in preventing sudden cardiac death in patients with left ventricular systolic dysfunction and heart failure: A meta-analysis of > 35,000 patients

Background

Patients with left ventricular systolic dysfunction (LVSD) are at high risk of sudden cardiac death (SCD). Implantable cardioverter defibrillators (ICDs) have an important role in preventing SCD in selected patients with LVSD and chronic heart failure (CHF). Drug therapies for LVSD and CHF also appear to also be useful in reducing SCD. However, the magnitude of benefit of these approaches on SCD is uncertain. We therefore conducted a meta-analysis comparing the effect on SCD achieved by ICDs versus medical therapies, additional to standard background medical therapies including ACE inhibitors and/or beta-blockers (BBs).

Methods

Our meta-analysis included trials of > 100 patients with reduced left ventricular ejection fraction (LVEF), i.e., < 40%. Fourteen randomized controlled trials met the criteria for meta-analysis, 10 involving medical therapies (angiotensin receptor blockers [ARBs], mineralocorticoid receptor antagonists [MRAs], ivabradine, n3-polyunsaturated fatty acid [PUFA], ferric carboxymaltose and aliskiren) and four involving ICDs. Results were pooled using the Mantel–Haenszel random effects method.

Results

Drug therapy (n = 36,172) reduced the risk of SCD overall (risk ratio (RR) = 0.89, 95% confidence interval (CI) = 0.82–0.98, p = 0.02) when compared to placebo. MRAs alone were most effective in reducing SCD (n = 11,032, RR = 0.79 [0.68–0.91], p = 0.001). ICD insertion greatly reduced SCD (n = 4,269, RR = 0.39 [0.30–0.51], p < 0.00001) compared with placebo. The difference in treatment effect between the ICD and drug therapy was significant (p < 0.002), and between ICD and MRAs (p < 0.002).

Conclusions

Drug therapies when added to a standard background regimen comprising ACE inhibitor and/or BB reduced SCD overall and MRAs alone were most effective in this regard. ICDs were more effective than drugs in SCD abrogation. However, the added procedural morbidity and the cost of ICD need to be considered in decision-making re-approach to SCD reduction in the individual patient.     

Intravenous immunoglobulin does not reduce left ventricular remodeling in patients with myocardial dysfunction during hospitalization after acute myocardial infarction

Background

Left ventricular (LV) remodeling takes place after acute myocardial infarction (MI), potentially leading to overt heart failure (HF). Enhanced inflammation may contribute to LV remodeling. Our hypothesis was that the immunomodulating effects of intravenous immunoglobulin (IVIg) would be beneficial in patients with impaired myocardial function after MI by reducing myocardial remodeling and improving myocardial function.

Methods

Sixty-two patients with acute MI treated by percutaneous coronary intervention, with depressed LV ejection fraction (LVEF) were randomized in a double-blinded fashion to IVIg as induction therapy and thereafter as monthly infusions or placebo for 26 weeks. The primary end point was changes in LVEF from baseline to 6 months as assessed by MRI.

Results

Our main findings were: (i) LVEF increased significantly from 38 ± 10 (mean ± SD) to 45 ± 13% after IVIg and from 42 ± 9 to 49 ± 12% after placebo with no difference between the groups. (ii) The scar area decreased significantly by 3% and 5% in the IVIg and placebo group, respectively, with no difference between the groups. (iii) During the induction therapy (baseline to day 5), IVIg induced both inflammatory (e.g., increase in tumor necrosis factor α and monocyte chemoattractant protein-1) and anti-inflammatory (e.g., increase in interleukin-10 and decrease in leukocyte counts) variables, but during maintenance therapy there were no differences in changes of inflammatory mediators between IVIg and placebo.

Conclusions

IVIg therapy after ST elevation MI managed by primary PCI does not affect LV remodeling or function. This illustrates the challenges of therapeutic intervention directed against the cytokine network, to prevent post-MI remodeling.     

Dietary ellagic acid improves oxidant-induced endothelial dysfunction and atherosclerosis: Role of Nrf2 activation

Background

Oxidative stress-induced vascular endothelial cell injury is a major factor in the pathogenesis of atherosclerosis. Several evidences indicate that ellagic acid (EA), a phenolic compound, contributes to cardiovascular health. This study was to investigate the effects of EA on endothelial dysfunction and atherosclerosis via antioxidant-related mechanisms.

Methods

In animal studies, wild-type (WT) C57BL/6 mice and apolipoprotein E-deficient mice (ApoE^−/−) mice were fed: a high-fat (21%) diet (HFD) or a HFD plus with EA (HFD + EA), for 14 weeks. Vascular reactivity was studied in mice aortas. The effect of EA in human umbilical vein endothelial cells (HAECs) exposed to hypochlorous acid (HOCl) was also investigated.

Results

Compared with animals on HFD alone, EA attenuated atherosclerosis in WT mice. In aortic rings from two mice models, EA significantly improved endothelium-dependent relaxation and attenuated HOCl-induced endothelial dysfunction. Besides, EA significantly improved nitric oxide synthase activity, antioxidant capacity and markers of endothelial dysfunction in plasma. Western blot analysis showed that EA increased NF-E2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) expression in the aortas (P < 0.05). In a separate experiment, EA did not protect against HOCl-induced endothelial dysfunction in arteries obtained from Nrf2 gene knockout mice compared with WT mice. In HAECs, EA prevented HOCl-induced cellular damage and induced HO-1 protein expression, and these effects markedly abolished by the siRNA of Nrf2.

Conclusions

Our results provide further support for the protective effects of dietary EA particularly oxidant-induced endothelial dysfunction and atherosclerosis partly via Nrf2 activation.     

Cardiac resynchronization therapy and AV optimization increase myocardial oxygen consumption,but increase cardiac function more than proportionally

Background

The mechanoenergetic effects of atrioventricular delay optimization during biventricular pacing (“cardiac resynchronization therapy”, CRT) are unknown.

Methods

Eleven patients with heart failure and left bundle branch block (LBBB) underwent invasive measurements of left ventricular (LV) developed pressure, aortic flow velocity-time-integral (VTI) and myocardial oxygen consumption (MVO₂) at 4 pacing states: biventricular pacing (with VV 0 ms) at AVD 40 ms (AV-40), AVD 120 ms (AV-120, a common nominal AV delay), at their pre-identified individualised haemodynamic optimum (AV-Opt); and intrinsic conduction (LBBB).

Results

AV-120, relative to LBBB, increased LV developed pressure by a mean of 11(SEM 2)%, p = 0.001, and aortic VTI by 11(SEM 3)%, p = 0.002, but also increased MVO2 by 11(SEM 5)%, p = 0.04.AV-Opt further increased LV developed pressure by a mean of 2(SEM 1)%, p = 0.035 and aortic VTI by 4(SEM 1)%, p = 0.017. MVO2 trended further up by 7(SEM 5)%, p = 0.22.Mechanoenergetics at AV-40 were no different from LBBB.The 4 states lay on a straight line for Δexternal work (ΔLV developed pressure × Δaortic VTI) against ΔMVO2, with slope 1.80, significantly > 1 (p = 0.02).

Conclusions

Biventricular pacing and atrioventricular delay optimization increased external cardiac work done but also myocardial oxygen consumption. Nevertheless, the increase in cardiac work was ~ 80% greater than the increase in oxygen consumption, signifying an improvement in cardiac mechanoenergetics. Finally, the incremental effect of optimization on external work was approximately one-third beyond that of nominal AV pacing, along the same favourable efficiency trajectory, suggesting that AV delay dominates the biventricular pacing effect — which may therefore not be mainly “resynchronization”.     

Minimal important difference for 6-minute walk test distances among patients with chronic heart failure

Background

The 6-minute walk test (6WT) is an established tool in the assessment of endurance and prognosis in patients with chronic heart failure (CHF). For these patients there is very limited data on biological variation of 6WT distances. We determined the minimal important difference (MID) for the 6WT in patients with stable systolic CHF.

Methods

Two cohorts of patients with stable systolic CHF were included from the outpatients' clinic of the University of Heidelberg. In these cohorts, two 6WT measurements were performed – in cohort 1 (n = 461) 180 days and in cohort 2 (n = 512) 365 days apart. Stability was defined as the absence of clinical events (3 months before the first test, between both tests, and 6 months after the second test) and stability of symptoms (NYHA) between tests. Using a standard error of measurement (SEM)-based approach, we determined the MID for both cohorts.

Results

The intraclass correlation coefficient was 0.89 at 180 days and 0.88 at 365 days. The results were consistent for groups stratified for age, gender, etiology of CHF, and individual NYHA class. The MID for the 6WT in stable CHF patients was 35 m and 37 m between presentation and 180 and 365 days, respectively.

Conclusion

Submaximal exercise capacity as represented by the 6WT varies little in stable CHF patients for up to 1-year intervals. The MID for changes in 6WT values in patients with stable CHF over a period of 6 to 12 months is ~ 36 m.     

Cross-talk between the heart and adipose tissue in cachectic heart failure patients with respect to alterations in body composition: A prospective study

Objectives

Cardiac cachexia (CC) is associated with changes in body composition. Lipolysis and increased energy expenditure caused by A- and B natriuretic peptides (NPs) have been suggested to play a role in CC. We tested the hypothesis that neurohormones and adipokines are associated with body composition in CC and that a progressive loss of fat free mass (FFM) and fat mass (FM) takes place.

Methods

Body composition with regard to FFM, FM, and body fat distribution was assessed by dual energy X-ray absorptiometry (DXA) in 19 non-diabetic patients with chronic heart failure (CHF) and CC and 38 controls (non-cachectic CHF and individuals with prior myocardial infarction-both n = 19) who were followed for 12 months. Biomarkers of neurohormonal stimulation, inflammation, and endothelial dysfunction were measured.

Results

N-terminal proBNP (NT-proBNP), midregional proANP (MR-proANP), and total adiponectin were elevated in CHF (p < 0.001) and correlated inversely to BMI and FM. An inverse correlation was observed between pro-adrenomedullin (MR-proADM) and FFM. During follow up body weight was unaltered in all groups even though FM increased by 1.35 kg (p < 0.05) and FFM decreased by 0.5 kg (p < 0.05) in CC patients. The latter correlated inversely to baseline NT-proBNP, MR-proANP, and MR-proADM (p < 0.05). No correlation to changes in FM was found.

Conclusions

FM was associated with plasma NPs and total adiponectin at baseline; whereas changes in FM and FFM did not correlate to changes in NPs or adiponectin during follow up. Prospectively, FFM decreased but FM increased, despite stable body weight in CC.     

Correlation between vectorcardiographic measures and cardiac magnetic resonance imaging of the left ventricle in an implantable cardioverter defibrillator population

Background

Measures of vectorcardiographic changes and LV remodelling have been associated with arrhythmic risk. However the correlation between the two modalities is not well characterised.

Methods

We correlated spatial QRS-T angle and ventricular gradient with cardiac MRI derived LV global measures and scar pattern in 66 ICD recipients.

Results

Spatial QRS-T angle was significantly larger in patients with ischaemic scar than those without scar (150° ± 22° vs. 119° ± 46°, p = 0.01). Larger spatial QRS-T angle was also correlated with more depressed LV function, more dilated LV and larger LV mass. Ventricular gradient azimuth was significantly different between patients with no scar, non-ischaemic scar and ischaemic scar (20° ± 49° vs. 38° ± 62° vs. 65° ± 48°, p = 0.009), but independent of spatial QRS-T angle and LV structure.

Conclusions

Spatial QRS-T angle and ventricular gradient are partially related to LV structural properties. Further investigation is warranted to examine their comparative and combined prognostic value in risk stratification of ventricular arrhythmias.     

Algisyl-LVR™ with coronary artery bypass grafting reduces left ventricular wall stress and improves function in the failing human heart

Background

Left ventricular (LV) wall stress reduction is a cornerstone in treating heart failure. Large animal models and computer simulations indicate that adding non-contractile material to the damaged LV wall can potentially reduce myofiber stress. We sought to quantify the effects of a novel implantable hydrogel (Algisyl-LVR™) treatment in combination with coronary artery bypass grafting (i.e. Algisyl-LVR™ + CABG) on both LV function and wall stress in heart failure patients.

Methods and results

Magnetic resonance images obtained before treatment (n = 3), and at 3 months (n = 3) and 6 months (n = 2) afterwards were used to reconstruct the LV geometry. Cardiac function was quantified using end-diastolic volume (EDV), end-systolic volume (ESV), regional wall thickness, sphericity index and regional myofiber stress computed using validated mathematical modeling. The LV became more ellipsoidal after treatment, and both EDV and ESV decreased substantially 3 months after treatment in all patients; EDV decreased from 264 ± 91 ml to 146 ± 86 ml and ESV decreased from 184 ± 85 ml to 86 ± 76 ml. Ejection fraction increased from 32 ± 8% to 47 ± 18% during that period. Volumetric-averaged wall thickness increased in all patients, from 1.06 ± 0.21 cm (baseline) to 1.3 ± 0.26 cm (3 months). These changes were accompanied by about a 35% decrease in myofiber stress at end-of-diastole and at end-of-systole. Post-treatment myofiber stress became more uniform in the LV.

Conclusions

These results support the novel concept that Algisyl-LVR™ + CABG treatment leads to decreased myofiber stress, restored LV geometry and improved function.