Electrocardiographic characteristics in patients with heart failure and normal ejection fraction: A systematic review and meta-analysis.

BACKGROUND: Little is known about ECG abnormalities in patients with heart failure and normal ejection fraction (HeFNEF) and how they relate to different etiologies or outcomes. METHODS AND RESULTS: We searched the literature for peer-reviewed studies describing ECG abnormalities in HeFNEF other than heart rhythm alone. Thirty five studies were identified and 32,006 participants. ECG abnormalities reported in patients with HeFNEF include atrial fibrillation (prevalence 12%-46%), long PR interval (11%-20%), left ventricular hypertrophy (LVH, 10%-30%), pathological Q waves (11%-18%), RBBB (6%-16%), LBBB (0%-8%), and long JTc (3%-4%). Atrial fibrillation is more common in patients with HeFNEF compared to those with heart failure and reduced ejection fraction (HeFREF). In contrast, long PR interval, LVH, Q waves, LBBB, and long JTc are more common in patients with HeFREF. A pooled effect estimate analysis showed that QRS duration ≥120 ms, although uncommon (13%-19%), is associated with worse outcomes in patients with HeFNEF. CONCLUSIONS: There is high variability in the prevalence of ECG abnormalities in patients with HeFNEF. Atrial fibrillation is more common in patients with HeFNEF compared to those with HeFREF. QRS duration ≥120 ms is associated with worse outcomes in patients with HeFNEF. Further studies are needed to address whether ECG abnormalities correlate with different phenotypes in HeFNEF.

Missed opportunity? Worsening breathlessness as a harbinger of death: a cohort study.

The aim of the study was to explore trajectories of breathlessness intensity by function and life-limiting illness diagnosis in the last 3 weeks of life in palliative care patients.A prospective, consecutive cohort study obtained point-of-care data of patients of Silver Chain Hospice Care Service (Perth, Australia) over the period 2011-2014 (n=6801; 51 494 data-points). Breathlessness intensity (0-10 numerical rating scale) and physical function (Australia-modified Karnofsky Performance Status (AKPS)) were measured at each visit. Time was anchored at death. Breathlessness trajectory was analysed by physical function and diagnosis using mixed effects regression.Mean±sd age was 71.5±15.1 years and 55.2% were male, most with cancer. The last recorded AKPS was >40 for 26.8%. Breathlessness was worst in people with cardiorespiratory disease and AKPS >40, and breathlessness in the last week of life increased most in this group (adjusted mean 2.92 versus all others 1.51; p=0.0001). The only significant interaction was with diagnosis and function in the last week of life (p<0.0001).Breathlessness is more intense and increases more in people with better function and cardiorespiratory disease immediately before death. Whether there are reversible causes for these people should be explored prospectively. Omitting function from previous population estimates may have overestimated breathlessness intensity for many patients in the days preceding death.

Postmortem ICD interrogation in mode of death classification.

BACKGROUND: The definition of sudden death due to arrhythmia relies on the time interval between onset of symptoms and death. However, not all sudden deaths are due to arrhythmia. In patients with an implantable cardioverter defibrillator (ICD), postmortem device interrogation may help better distinguish the mode of death compared to a time-based definition alone. OBJECTIVE: This study aims to assess the proportion of "sudden" cardiac deaths in patients with an ICD that have confirmed arrhythmia. METHODS: We conducted a literature search for studies using postmortem ICD interrogation and a time-based classification of the mode of death. A modified QUADAS-2 checklist was used to assess risk of bias in individual studies. Outcome data were pooled where sufficient data were available. RESULTS: Our search identified 22 studies undertaken between 1982 and 2015 with 23,600 participants. The pooled results (excluding studies with high risk of bias) suggest that ventricular arrhythmias are present at the time of death in 76% of "sudden" deaths (95% confidence interval [CI] 67-85; range 42-88). CONCLUSION: Postmortem ICD interrogation identifies 24% of "sudden" deaths to be nonarrhythmic. Postmortem device interrogation should be considered in all cases of unexplained sudden cardiac death.

Clinical and prognostic association of total atrial conduction time in patients with heart failure: a report from Studies Investigating Co-morbidities Aggravating Heart Failure.

BACKGROUND: The total atrial conduction time can be measured as the time from the onset of the P wave on the ECG to the peak of the A wave recorded at the mitral annulus using tissue Doppler imaging (A'; P-A'TDI); when prolonged, it might predict incident atrial fibrillation. METHODS: We measured P-A'TDI in outpatients with heart failure and sinus rhythm enrolled in the SICA-HF programme. RESULTS: P-A'TDI measured at the lateral mitral annulus was longer in patients with HF with reduced [LVEF<50%, N = 141; 126 (112-146) ms; P = 0.005] or preserved left ventricular ejection fraction [LVEF>50% and NT-proBNP > 125 ng/l, N = 71; 128 (108-145) ms; P = 0.026] compared to controls [N = 117; 120 (106-135) ms]. Increasing age, left atrial volume and PR interval were independently associated with prolonged P-A'TDI. During a median follow-up of 1251 (956-1602) days, 73 patients with heart failure died (N = 42) or developed atrial fibrillation (N = 31). In univariable analysis, P-A'TDI was associated with an increased risk of the composite outcome of death or atrial fibrillation, but only increasing log [NT-proBNP], age and more severe symptoms (NYHA III vs. I/II) were independently related to this outcome. Patients in whom both P-A'TDI and left atrial volume were above the median (127 ms and 64 ml, respectively) had the highest incidence of atrial fibrillation (hazard ratio 6.61, 95% CI 2.27-19.31; P < 0.001 compared with those with both P-A'TDI and LA volume below the median). CONCLUSION: Measuring P-A'TDI interval identifies patients with chronic heart failure at higher risk of dying or developing atrial fibrillation during follow-up.

The HF-CGM Study: An Analysis of Cardiogoniometric Axes in Patients With Cardiac Resynchronization Therapy.

GOAL: The HF-CGM is a proof-of-principle study to investigate whether cardiogoniometry (CGM), a three-dimensional electrocardiographic method, can differentiate between pacing modes in patients with cardiac resynchronization therapy (CRT). METHODS: At a tertiary cardiology center, CGM recordings were performed using four pacing modes: no pacing; right ventricular (RV) pacing; left ventricular (LV) pacing, and biventricular (BIV) pacing. Three orthogonal CGM planes orientated to the long axis (XY), the frontal plane (YZ), and the short axis (XZ) of the heart were constructed, and the direction of the QRS-axis was calculated for each pacing mode in each plane. During BIV pacing, the direction of CGM QRS-axis was compared between patients with optimal and nonoptimal 12-lead pacing variables. RESULTS: Twenty-two participants (aged 71.5 ± 10.8; 77.3% male, LVEF 29 ± 7%) were consecutively recruited. Only QRS-axis measured in the XY plane could significantly distinguish between all three pacing modes versus no pacing. Mean QRS-axis in the XY plane with pacing off and during RV pacing was leftward and basal; LV pacing was apical; and BIV pacing was rightward and basal. There was a statistically significant difference in the direction of the QRS-axis between patients with optimal versus nonoptimal paced QRS morphology in the XY plane (rightward and basal versus inconsistent). SIGNIFICANCE: CGM recorded in the XY plane can accurately detect differences between ventricular pacing sites. It may also be able to identify patients with a CRT device in situ who have optimal response.

Prevalence, predictors, and prognostic implications of PR interval prolongation in patients with heart failure.

AIMS: To determine the prevalence, incidence, predictors, and prognostic implications of PR interval prolongation in patients referred with suspected heart failure. METHODS AND RESULTS: Consecutive patients referred with suspected heart failure were prospectively enrolled. After excluding patients with implantable cardiac devices and atrial fibrillation, 1420 patients with heart failure and reduced ejection fraction (HeFREF) [age: median 71 (interquartile range IQR 63-78) years; men: 71%; NT-ProBNP: 1319 (583-3378) ng/L], 1094 with heart failure and normal ejection fraction (HeFNEF) [age: 76 (70-82) years; men: 47%; NT-ProBNP: 547 (321-1171) ng/L], and 1150 without heart failure [age: 68 (60-75) years; men: 51%; NT-ProBNP: 86 (46-140) ng/L] were included. The prevalence of first-degree heart block [heart rate corrected PR interval (PRc) > 200 ms] was higher in patients with heart failure (21% HeFREF, 20% HeFNEF, 9% without heart failure). In patients with HeFREF or HeFNEF, longer baseline PRc was associated with greater age, male sex, and longer QRS duration, and, in those with HeFREF, treatment with amiodarone or digoxin. Patients with heart failure in the longest PRc quartile had worse survival compared to shorter PRc quartiles, but PRc was not independently associated with survival in multivariable analysis. For patients without heart failure, shorter baseline PRc was independently associated with worse survival. CONCLUSION: PRc prolongation is common in patients with HeFREF or HeFNEF and associated with worse survival, although not an independent predictor of outcome. The results of clinical trials investigating the therapeutic potential of shortening the PR interval by pacing are awaited.

Outcomes Related to First-Degree Atrioventricular Block and Therapeutic Implications in Patients With Heart Failure.

The prevalence of first-degree atrioventricular block in the general population is approximately 4%, and it is associated with an increased risk of atrial fibrillation. Cardiac pacing for any indication in patients with first-degree heart block is associated with worse outcomes compared with patients with normal atrioventricular conduction. Among patients with heart failure, first-degree atrioventricular block is present in anywhere between 15% and 51%. Data from cardiac resynchronization therapy studies have shown that first-degree atrioventricular block is associated with an increased risk of mortality and heart failure hospitalization. Recent studies suggest that optimization of atrioventricular delay in patients with cardiac resynchronization therapy is an important target for therapy; however, the optimal method for atrioventricular resynchronization remains unknown. Understanding the role of first-degree atrioventricular block in the treatment of patients with heart failure will improve medical and device therapy.

Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit.

Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navß1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ.

Application of micro-computed tomography with iodine staining to cardiac imaging, segmentation, and computational model development.

Micro-computed tomography (micro-CT) has been widely used to generate high-resolution 3-D tissue images from small animals nondestructively, especially for mineralized skeletal tissues. However, its application to the analysis of soft cardiovascular tissues has been limited by poor inter-tissue contrast. Recent ex vivo studies have shown that contrast between muscular and connective tissue in micro-CT images can be enhanced by staining with iodine. In the present study, we apply this novel technique for imaging of cardiovascular structures in canine hearts. We optimize the method to obtain high-resolution X-ray micro-CT images of the canine atria and its distinctive regions-including the Bachmann's bundle, atrioventricular node, pulmonary arteries and veins-with clear inter-tissue contrast. The imaging results are used to reconstruct and segment the detailed 3-D geometry of the atria. Structure tensor analysis shows that the arrangement of atrial fibers can also be characterized using the enhanced micro-CT images, as iodine preferentially accumulates within the muscular fibers rather than in connective tissues. This novel technique can be particularly useful in nondestructive imaging of 3-D cardiac architectures from large animals and humans, due to the combination of relatively high speed ( ~ 1 h/per scan of the large canine heart) and high voxel resolution (36 µm) provided. In summary, contrast micro-CT facilitates fast and nondestructive imaging and segmenting of detailed 3-D cardiovascular geometries, as well as measuring fiber orientation, which are crucial in constructing biophysically detailed computational cardiac models.

Contrast enhanced micro-computed tomography resolves the 3-dimensional morphology of the cardiac conduction system in mammalian hearts.

The general anatomy of the cardiac conduction system (CCS) has been known for 100 years, but its complex and irregular three-dimensional (3D) geometry is not so well understood. This is largely because the conducting tissue is not distinct from the surrounding tissue by dissection. The best descriptions of its anatomy come from studies based on serial sectioning of samples taken from the appropriate areas of the heart. Low X-ray attenuation has formerly ruled out micro-computed tomography (micro-CT) as a modality to resolve internal structures of soft tissue, but incorporation of iodine, which has a high molecular weight, into those tissues enhances the differential attenuation of X-rays and allows visualisation of fine detail in embryos and skeletal muscle. Here, with the use of a iodine based contrast agent (I(2)KI), we present contrast enhanced micro-CT images of cardiac tissue from rat and rabbit in which the three major subdivisions of the CCS can be differentiated from the surrounding contractile myocardium and visualised in 3D. Structures identified include the sinoatrial node (SAN) and the atrioventricular conduction axis: the penetrating bundle, His bundle, the bundle branches and the Purkinje network. Although the current findings are consistent with existing anatomical representations, the representations shown here offer superior resolution and are the first 3D representations of the CCS within a single intact mammalian heart.