Nigel Lewis

Progression of atrial remodeling in patients with high-burden atrial fibrillation: Implications for early ablative intervention.

BACKGROUND Advanced atrial remodeling predicts poor clinical outcomes in human atrial fibrillation (AF). OBJECTIVE The purpose of this study was to define the magnitude and predictors of change in left atrial (LA) structural remodeling over 12 months of AF. METHODS Thirty-eight patients with paroxysmal AF managed medically (group 1), 20 undergoing AF ablation (group 2), and 25 control patients with no AF history (group 3) prospectively underwent echocardiographic assessment of strain variables of LA reservoir function at baseline and at 4, 8, and 12 months. In addition, P-wave duration (Pmax,, Pmean) and dispersion (Pdis) were measured. AF burden was quantified by implanted recorders. Twenty patients undergoing ablation underwent electroanatomic mapping (mean 333 ± 40 points) for correlation with LA strain. RESULT Group 1 demonstrated significant deterioration in total LA strain (26.3% ± 1.2% to 21.7% ± 1.2%, P < .05) and increases in Pmax (132 ± 3 ms to 138 ± 3 ms, P < .05) and Pdis (37 ± 2 ms to 42 ± 2 ms, P < .05). AF burden ≥10% was specifically associated with decline in strain and with P-wave prolongation. Conversely, group 2 manifest improvement in total LA strain (21.3% ± 1.7% to 28.6% ± 1.7%, P <.05) and reductions in Pmax (136 ± 4 ms to 119 ± 4 ms, P < .05) and Pdis (47 ± 3 ms to 32 ± 3 ms, P < .05). Change was not significant in group 3. LA mean voltage (r = 0.71, P = .0005), percent low voltage electrograms (r = -0.59, P = .006), percent complex electrograms (r = -0.68, P = .0009), and LA activation time (r = -0.69, P = .001) correlated with total strain as a measure of LA reservoir function. CONCLUSION High-burden AF is associated with progressive LA structural remodeling. In contrast, AF ablation results in significant reverse remodeling. These data may have implications for timing of ablative intervention.

Cardiovascular outcomes in Fabry disease are linked to severity of chronic kidney disease

Objectives Assess the impact of end-stage renal disease (chronic kidney disease stage 5 (CKD5)) on cardiovascular outcomes in patients with Fabry disease on enzyme replacement therapy. Background Fabry disease, an X-linked lysosomal storage disease, causes hypertrophic cardiomyopathy and cardiovascular dysfunction. Methods Cardiac and renal function of 25 male patients with Fabry disease were analysed at 0, 1, 2, 5, 7 and 10 years after initiation of treatment. Patients were grouped at baseline into those with CKD5 (n=10) and those without (n=15). ECG and echocardiography were performed 6 and 12 monthly, respectively, while renal function was measured yearly. Results After 10 years of treatment, cardiac and renal function in non-CKD5 patients remained unchanged. In contrast, CKD5 was associated with worse baseline cardiac parameters and progressive LV hypertrophy. LV mass index grew by 35.4±31.8 g/m2.7 in CKD5 versus 5.7±7.9 g/m2.7, p=0.044 in non-CKD5, predominantly due to increased interventricular septal wall thickness (7.7±5.5 mm vs 1.3±1.7 mm, p=0.003). Cardiovascular events, including sudden death, arrhythmia and pacing device insertion, occurred in 100% patients with CKD5 (21 events) and 26% non-CKD5 patients (7 events), p<0.0001. Additionally, estimated LV filling pressure (E/Ea) was significantly higher in patients having cardiovascular events (21.1±7.7 vs 12.5±4.5, p=0.008) irrespective of renal function. Conclusions End-stage renal disease was the strongest indicator of cardiovascular disease progression in Fabry disease. Enzyme replacement initiated prior to CKD5 was associated with stability in cardiac and renal disease while patients with CKD5 showed ongoing deterioration. Additionally, E/Ea ≥15 may predict risk of cardiac events.

Cardiac Functional Reserve is Diminished in Growth Hormone-Deficient Adults

Various studies have shown that patients with severe growth hormone deficiency (GHD) have diverse changes in left ventricular (LV) size or performance but so far there is no direct indication of cardiac reserve ability to maintain the circulation during peak exercise. We tested the hypothesis that patients with severe GHD have reduced cardiac reserve function compared with healthy controls. Eighteen patients with severe GHD were studied and compared with 18 age-, sex-, and body mass index (BMI)-matched healthy controls. Peak cardiac power and cardiorespiratory fitness were investigated using noninvasive hemodynamic measurements during maximal cardiopulmonary exercise testing. Compared with matched controls, the cardiac power of GHD patients during exercise to volitional exhaustion was significantly reduced by 15% (mean +/- SD: 4.4 +/- 1.0 watts (W) vs. 5.2 +/- 1.0 W, P= 0.02), despite attaining similar aerobic exercise peaks (VO(2max), GHD: 2390 +/- 822 mL/min vs. controls: 2461 +/- 872 mL/min, P= 0.80) and similar peak respiratory exchange ratios. The lower peak cardiac power could not be accounted for by peripheral alterations because both groups reached similar peak exercise systemic vascular resistances. Patients with GHD also had lower cardiac chronotropic reserve (peak heart rate: 154 +/- 21 bpm vs. 174 +/- 11 bpm, P= 0.001) and a lower cardiac pressure-generating capacity (systolic blood pressure [SBP] 160 +/- 25 mmHg vs. 200 +/- 15 mmHg, P < 0.0001). Using this robust noninvasive method of assessing functional cardiac pumping capacity we have for the first time shown that patients with severe GHD have a significantly impaired cardiac functional reserve associated with chronotropic incompetence and impaired pressure-generating capacity.

Confusion over thiazolidinedione-induced heart failure: need for a better definition of heart failure

Evaluation of: Erdmann E, Wilcox RG. Weighing up the cardiovascular benefits of thiazolidinedione therapy: the impact of increased risk of heart failure. Eur. Heart J. 29(1), 12–20 (2008). Thiazolidinediones (TZDs) reduce insulin resistance through the modulation of peroxisome proliferator-activated receptor (PPAR)-γ activity and are, therefore, used for the treatment of individuals with Type 2 diabetes. TZDs have been blamed for inducing heart failure (HF) and are contraindicated in patients with impaired ventricular function. Whether precipitation of HF by TZDs is overestimated or not remains hotly debated in the scientific community. One message from the TZD–HF debacle is that current definitions of HF lack scientific rigour as they fail to assess cardiac organ function directly using a representative and reliable method. Once cardiologists reappraise and update the current definition of HF, appropriate steps can then be taken to answer the question of whether TZDs really induce true HF.

The Cardiac Genetics Clinic: a model for multidisciplinary genomic medicine

Objectives: To describe patient characteristics, standard operating procedure, and uptake of genetic testing at the multidisciplinary Cardiac Genetics Clinic (CGC) at the Royal Melbourne Hospital during its first 6 years.

Atrial Fibrillation reduces the Functional REServe of the Heart by a fifth: A pilot FRESH-AF study

The advent of catheter ablation has reignited the controversy about whether rhythm or rate control should be the preferred mode of therapy for atrial fibrillation (AF) [1]. It is well known that compared to sinus rhythm (SR), AF is associated with increased mortality and morbidity including stroke, heart failure, and impaired quality of life. Furthermore, patients may experience adverse effects from drug treatment that may negate thebeneficial effects ofmaintaining SR [2].What is still unknown is inwhatways and by howmuch overall cardiac function is impairedwhen the atrial “kick” in SR is lost after the onset of AF. To fill this gap in knowledge, it is essential to assess cardiac functionnot onlyat rest but also during maximal stress, and not merely piecemeal aspects of cardiac function. This can be achieved by conducting full cardiopulmonary exercise testing (CPX) in combination with non-invasive evaluation of central haemodynamics [3]. Thiswouldprovide a quantitative assessment of aerobic physical exercise capacity represented by peak O2 consumption (VO2max), together with peak cardiac power output (CPOmax) which measures the overall cardiac dysfunction [4], and is by far the strongest predictor of prognosis in heart failure patients [5]. As metabolic and circulatory demands increase during severe exercise, patients with AF have lower cardiovascular reserve. Previous studies have shown that VO2max improved by 5–13% after restoration of SR in patients with AF [6], buthowmuchcardiac functional gain is achieved thereby is still unknown. We therefore measured changes in CPOmax after successful DC cardioversion (DCCv) in patients with optimally rate-controlled AF. In so doing, we tested the hypothesis that the cardiac pumping capability of patients in AF is diminished by about a fifth. Twelve unselected ambulatory patients (10 males, age: 57.5 ± 13.7 (mean ± SD) years) with symptomatic persistent AF recruited from outpatient clinics underwent full CPX with measurements of non-invasive haemodynamics before and after successful DCCv. The aetiologies (including overlaps) of their AF were ischaemic heart disease (17%), hypertension (25%), LV dysfunction (42%), valve disease (25%), lone AF (25%), and obesity (BMI N 35, 25%). None of the patients had previous catheter ablation, or any contraindication to undergomaximal exercise, such as significant outflow obstruction, haemodynamically serious structural heart disease, uncontrolled ventricular tachyarrhythmia, uncontrolled hypertension, limiting symptoms of ischaemic heart disease, inability or deemed unsafe to exercise on treadmill, contraindications to electrical cardioversion or full anticoagulation, or inability to provide full informed consent. Standardexerciseparametersweremeasuredaspartof an incremental cardiopulmonary exercise test performed on a Trackmaster TMX425 treadmill (Full Vision, Kansas, USA) using the Bruce or modified Bruce protocol, as previously described [3]. Rates of oxygen consumption (VO2) and other gaseous exchanges were recorded breath-by-breath using the Medgraphics Ultima CardiO2 analytic system (Medgraphics, Minnesota, USA). Using the CO2-rebreathing technique (indirect Fick), cardiac output were measured at rest and during peak exercise. Mean arterial pressure was calculated from the equation, MAP=DBP+ 0.412 ∗ (SBP− DBP) [7]. CPOmax in watts is the product of peak cardiac output (COmax in l.min−1)multiplied by theMAP inmm Hg at peak exercisemultiplied by a conversion factor (2.22 × 10−3) [8]. A paired sample t-test was used to assess the change in cardiac reserve variables pre and post DCCv. This study was approved by the National Research Ethics Service Committee for Yorkshire & Humber in Leeds East. After successful cardioversion, subjectively all patients claimed to feel better and more energetic and, as shown in Table 1, objectively their treadmill exercise duration increased by 19.3% (P b 0.05), coupled with an improvement in peak O2 consumption by 16.5% (P b 0.01). Their resting ventricular rate decreased from 83.1 ±20.3 to 66.9 ± 20.5 min− 1 (P b 0.05), while peak exercise HR decreased from 163 ± 42 to 128 ± 18 min−1 to (P b 0.05). Secondarily, these negative chronotropic effects led to heightened stroke volume at peak exercise by 46% (P b 0.0001), thereby raising the peak cardiac output by 16.5% (P b 0.0001). Due to a concomitantly greater

New evidence of cardiac dysfunction associated with renal impairment

frequency) in 20 (65%) cases. Electrocution was a work-related accident in 22 (70%) cases. Superficial burns were observed in 27 (87%) patients and did not require admission to a specialized burn care unit. Cardiac troponin Ic level (normal range b0.04 μg/ml) was increased in 5 (16%) patients to a mean of 0.09±0.03 μg/ml. Creatine kinase level was increased in 17 (55%) patients to a mean of 426±713 UI/l. Electrocardiogram abnormalities were observed in 26 (84%) cases: ventricular hypertrophy in 11, incomplete bundle branch block in 9, diffuse STsegment elevation in 6 and negative T waves in inferolateral leads in 13. Echocardiography was performed in only 2 patients and revealed mild septal hypertrophy (mean 13±2mm) without segmental wall-motion abnormalities orpericardial effusion. Standard treatment consistedof pain relievers and benzodiazepines to control anxiety. During a mean ICU stay of 1±0.5 day, none of the patients presented atrial or ventricular arrhythmias, heart failure or sudden death. After discharge, follow-up was available for 22 (71%) patients. During a mean follow-up of 30± 10months, none presented physical or psychological sequels related to electrocution. In our study, electrocardiographic changeswere frequent butwere not related to clinical symptoms suggestive of myocardial ischemia or pericarditis. Unfortunately, echocardiograms were rarely performed and we could not determine if these changes were due to cardiac injury or if they were non-specific. Their evolution after discharge is unknown. Creatine kinase elevation may be due to skeletal muscle injury and was more frequent than cardiac-specific troponin Ic elevation. The latter did not predictworse outcome since the initial course of all the patients in our series was uneventful and no complications occurred during follow-up. Our results suggest that systematic hospitalization and monitoring in ICU may not be mandatory after electrocution. Larger series are needed to better define the incidence and predictors of cardiac complications after electrocution to further determine the appropriate monitoring and treatment of these patients. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010;144:1–2).

Early and asymptomatic cardiac dysfunction in chronic kidney disease.

Background Heart failure (HF) is highly prevalent and associated with high mortality in chronic kidney disease (CKD). However, the pathophysiology of cardiac dysfunction in CKD, especially in the early asymptomatic stage, is not well understood. We studied subclinical cardiac dysfunction in asymptomatic CKD patients without comorbid cardiac disease or diabetes mellitus by evaluating peak cardiac performance. Methods In a cross-sectional study (n = 130) we investigated 70 male non-diabetic CKD patients (21 CKD stage 2-3a, 27 CKD stage 3b-4 and 22 CKD stage 5) employing specialized cardiopulmonary exercise testing to measure peak cardiac output and cardiac power output non-invasively. Data from 35 age-matched healthy male volunteers were obtained for comparison. In addition, as a positive control, data from 25 age-matched male HF patients in New York Heart Association class II and III were also obtained. Results The study subjects showed a graded reduction in peak cardiac power, with 6.13 ± 1.11 W in controls, 5.02 ± 0.78 W in CKD 2-3a, 4.59 ± 0.53 W in CKD 3b-4 and 4.02 ± 0.73 W in CKD 5, although not as impaired as in HF, with 2.34 ± 0.63 W (all P < 0.005 versus control). The central haemodynamic characteristics of the cardiac impairment in CKD mirrored that of HF, with reduced flow and pressure-generating capacities, reduced chronotropic reserve and impaired contractility. Conclusions The study demonstrates for the first time impaired peak cardiac performance and cardiac functional reserve in asymptomatic CKD patients. The evidence of myocardial dysfunction in the absence of comorbid cardiac disease and diabetes warrants further evaluation of current pathophysiological concepts of cardiovascular disease in CKD.

Reduced cardiac functional reserve and quality of life in adults with GH deficiency.

Introduction  Patients with severe GH deficiency (GHD) suffer with a reduced quality of life in addition to diverse changes in cardiac size and performance. So far, the cardiac reserve ability to maintain the circulation during peak exercise has not been measured. We tested the hypothesis that patients with severe GHD have reduced cardiac reserve function compared with healthy controls and that this could explain, in part, their reduced quality of life.

Restoration of sinus rhythm results in early and late improvements in the functional reserve of the heart following direct current cardioversion of persistent AF: FRESH-AF

BACKGROUND The improvement in cardiac physiological parameters after restoration of sinus rhythm in patients with persistent atrial fibrillation (AF) can be challenging to quantify. Overall cardiac function assessment is better assessed by peak cardiac power output (CPOpeak), rather than indirect measures of cardiac performance such as peak oxygen consumption (VO2peak). CPO was used to quantify improvement in cardiac function early and later following electrical cardioversion. METHODS AND RESULTS 29 patients with persistent AF underwent maximal treadmill cardiopulmonary exercise (CPEx) testing within 14days (±3) 8weeks (±3) following electrical cardioversion (DCCv). This enabled measurement of VO2peak, cardiac output (COpeak) and calculation of CPOpeak. Quality of life (QoL) data (EQ5D) was also recorded. Three patients attended for 2 CPEx tests and 3 were lost to follow-up (total n=26). Fourteen were successfully cardioverted and 12 remained in AF. In patients successfully cardioverted exercise duration increased significantly between all tests. CPOpeak, VO2peak, CO peak and QoL were improved significantly between Tests 1 and 2 (p<0.02) and Tests 1 and 3 (p<0.05). QoL improved by 15%. CONCLUSIONS Restoration of SR confers significant, early and sustained cardiac functional improvement following DCCv with a significant 14% increase in the calculated peak power output of the heart. Such increase in functional reserve suggests that pursuit of a rhythm control strategy in the treatment of AF may be warranted in terms of both improving quality of life and cardiac function with objective improvement of cardiac function.