Prolongation of atrio-ventricular node conduction in a rabbit model of ischaemic cardiomyopathy: Role of fibrosis and connexin remodelling.

Conduction abnormalities are frequently associated with cardiac disease, though the mechanisms underlying the commonly associated increases in PQ interval are not known. This study uses a chronic left ventricular (LV) apex myocardial infarction (MI) model in the rabbit to create significant left ventricular dysfunction (LVD) 8weeks post-MI. In vivo studies established that the PQ interval increases by approximately 7ms (10%) with no significant change in average heart rate. Optical mapping of isolated Langendorff perfused rabbit hearts recapitulated this result: time to earliest activation of the LV was increased by 14ms (16%) in the LVD group. Intra-atrial and LV transmural conduction times were not altered in the LVD group. Isolated AVN preparations from the LVD group demonstrated a significantly longer conduction time (by approximately 20ms) between atrial and His electrograms than sham controls across a range of pacing cycle lengths. This difference was accompanied by increased effective refractory period and Wenckebach cycle length, suggesting significantly altered AVN electrophysiology post-MI. The AVN origin of abnormality was further highlighted by optical mapping of the isolated AVN. Immunohistochemistry of AVN preparations revealed increased fibrosis and gap junction protein (connexin43 and 40) remodelling in the AVN of LVD animals compared to sham. A significant increase in myocyte-non-myocyte connexin co-localization was also observed after LVD. These changes may increase the electrotonic load experienced by AVN muscle cells and contribute to slowed conduction velocity within the AVN.

Long-term impact on healthcare resource utilization of statin treatment, and its cost effectiveness in the primary prevention of cardiovascular disease: a record linkage study.

AIMS: To assess the impact on healthcare resource utilization, costs, and quality of life over 15 years from 5 years of statin use in men without a history of myocardial infarction in the West of Scotland Coronary Prevention Study (WOSCOPS). METHODS: Six thousand five hundred and ninety-five participants aged 45-54 years were randomized to 5 years treatment with pravastatin (40 mg) or placebo. Linkage to routinely collected health records extended follow-up for secondary healthcare resource utilization to 15 years. The following new results are reported: cause-specific first and recurrent cardiovascular hospital admissions including myocardial infarction, heart failure, stroke, coronary revascularization and angiography; non-cardiovascular hospitalization; days in hospital; quality-adjusted life years (QALYs); costs of pravastatin treatment, treatment safety monitoring, and hospital admissions. RESULTS: Five years treatment of 1000 patients with pravastatin (40 mg/day) saved the NHS £710 000 (P < 0.001), including the cost of pravastatin and lipid and safety monitoring, and gained 136 QALYs (P = 0.017) over the 15-year period. Benefits per 1000 subjects, attributable to prevention of cardiovascular events, included 163 fewer admissions and a saving of 1836 days in hospital, with fewer admissions for myocardial infarction, stroke, heart failure and coronary revascularization. There was no excess in non-cardiovascular admissions or costs (or in admissions associated with diabetes or its complications) and no evidence of heterogeneity of effect over sub-groups defined by baseline cardiovascular risk. CONCLUSION: Five years' primary prevention treatment of middle-aged men with a statin significantly reduces healthcare resource utilization, is cost saving, and increases QALYs. Treatment of even younger, lower risk individuals is likely to be cost-effective.

Spectral microvolt T-wave alternans testing has no prognostic value in patients recently hospitalized with decompensated heart failure.

AIMS: Microvolt T-wave alternans (MTWA) testing identifies beat-to-beat fluctuations in T-wave morphology, which have been linked to ventricular arrhythmias. However, clinical studies have produced conflicting results and data in heart failure (HF) have been limited. The aim of this study was to determine the prevalence and incremental prognostic value of spectral MTWA testing in an unselected cohort of patients recently hospitalized with HF. METHODS AND RESULTS: Consecutive admissions with confirmed HF were recruited, and survivors were invited to attend 1 month post-discharge for MTWA testing. A total of 648 of 1003 enrolled patients returned for MTWA testing (58% male, mean age 71 years). Forty-nine per cent were ineligible due to AF, pacemaker dependency, or inability to exercise. Of the 330 MTWA test results, 30% were positive, 24% negative, and 46% indeterminate. Overall, 268 deaths occurred during a median follow-up of 3.1 (interquartile range 1.9-3.9) years. Of the ineligible patients, 48% died vs. 35% of eligible patients (P < 0.001). Of those patients with positive, negative, and indeterminate tests, 27, 35, and 40%, respectively, died (P = 0.12). Even when analysed as non-negative (positive/indeterminate) vs. negative, there was still no between-group difference in mortality (P = 0.95). MTWA results categorized as positive, negative, or indeterminate showed no incremental prognostic value in a multivariable model, which included BNP. Paradoxically, when compared in a binary fashion with a non-negative result, a negative test was an independent predictor of death, as was ineligibility for MTWA testing. CONCLUSION: Spectral MTWA testing was not widely applicable and failed to predict mortality, and so cannot be endorsed as a risk stratification tool in HF.

N-terminal pro-B-type natriuretic peptide and the prediction of primary cardiovascular events: results from 15-year follow-up of WOSCOPS.

AIMS: To test whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) was independently associated with, and improved the prediction of, cardiovascular disease (CVD) in a primary prevention cohort. METHODS AND RESULTS: In the West of Scotland Coronary Prevention Study (WOSCOPS), a cohort of middle-aged men with hypercholesterolaemia at a moderate risk of CVD, we related the baseline NT-proBNP (geometric mean 28 pg/mL) in 4801 men to the risk of CVD over 15 years during which 1690 experienced CVD events. Taking into account the competing risk of non-CVD death, NT-proBNP was associated with an increased risk of all CVD [HR: 1.17 (95% CI: 1.11-1.23) per standard deviation increase in log NT-proBNP] after adjustment for classical and clinical cardiovascular risk factors plus C-reactive protein. N-terminal pro-B-type natriuretic peptide was more strongly related to the risk of fatal [HR: 1.34 (95% CI: 1.19-1.52)] than non-fatal CVD [HR: 1.17 (95% CI: 1.10-1.24)] (P= 0.022). The addition of NT-proBNP to traditional risk factors improved the C-index (+0.013; P < 0.001). The continuous net reclassification index improved with the addition of NT-proBNP by 19.8% (95% CI: 13.6-25.9%) compared with 9.8% (95% CI: 4.2-15.6%) with the addition of C-reactive protein. N-terminal pro-B-type natriuretic peptide correctly reclassified 14.7% of events, whereas C-reactive protein correctly reclassified 3.4% of events. Results were similar in the 4128 men without evidence of angina, nitrate prescription, minor ECG abnormalities, or prior cerebrovascular disease. CONCLUSION: N-terminal pro-B-type natriuretic peptide predicts CVD events in men without clinical evidence of CHD, angina, or history of stroke, and appears related more strongly to the risk for fatal events. N-terminal pro-B-type natriuretic peptide also provides moderate risk discrimination, in excess of that provided by the measurement of C-reactive protein. Clinical trial registration WOSCOPS was carried out and completed prior to the requirement for clinical trial registration.

Amplitude Changes during Ventricular Fibrillation: A Mechanistic Insight.

INTRODUCTION: Clinically in ventricular fibrillation (VF), ECG amplitude, and frequency decrease as ischemia progresses and predict defibrillation success. In vitro ECG amplitude declines without ischemia, independent of VF frequencies. This study examines the contribution of cellular electrical activity and global organization to ECG amplitude changes during VF. METHODS AND RESULTS: Rabbit hearts were Langendorff-perfused (40 mL/min, Tyrode's solution) and loaded with RH237. During VF, ECG, and epicardial optical action potentials were recorded (photodiode array; 256 sites, 15 mm × 15 mm). After 60 s of VF, perfusion was either maintained, global ischemia produced by low-flow (6 mL/min), or solution [K(+)](o) raised to 8 mM. Peak-to-peak amplitude was determined for all signals. During VF, in control, ECG amplitude decreased to a steady-state (∼57% baseline), whereas in low-flow steady-state was not reached with the amplitude continuing to fall to 33% of baseline by 600 s. Optically, LV amplitude declined more than RV, reaching significance in control (LV vs. RV; 33 ± 5 vs. 63 ± 8%, p < 0.01). During VF in 8 mM [K(+)](o), amplitude changes were more complex; ECG amplitude increased with time (105 ± 13%), whilst LV amplitude decreased (60 ± 15%, p < 0.001). Microelectrode studies showed amplitude reduction in control and 8 mM [K(+)](o) (to ∼79 and ∼93% baseline, respectively). Evaluation of electrical coordination by cross-correlation of optical signals showed as VF progressed coordination reduced in control (baseline 0.36 ± 0.02 to 0.28 ± 0.003, p < 0.01), maintained in low-flow (0.41 ± 0.03 to 0.37 ± 0.005, p = NS) and increased in 8 mM [K(+)](o) (0.36 ± 0.02 to 0.53 ± 0.08, p < 0.05). CONCLUSION: ECG amplitude decline in VF is due to a combination of decreased systolic activation at the cellular level and increased desynchronization of inter-cellular electrical activity.

Profile of microvolt T-wave alternans testing in 1003 patients hospitalized with heart failure.

AIMS: Observational studies in selected populations have suggested that microvolt T-wave alternans (MTWA) testing may identify patients with heart failure (HF) at risk of sudden cardiac death. The aims of this study were to investigate the utility of MTWA testing in an unselected population of patients with HF and to evaluate the clinical characteristics associated with the MTWA results. METHODS AND RESULTS: A total of 1003 patients hospitalized with decompensated HF were enrolled. MTWA testing was planned 1 month post-discharge; 648 patients returned for MTWA testing. Mean age was 70.8 ± 10.6 years and 58% were male. Of these patients who returned, 318 (49%) were ineligible for MTWA testing due to atrial fibrillation (AF), pacemaker dependency, or physical inability to undertake the test. Of the MTWA tests, 100 (30%) were positive, 78 (24%) were negative, and 152 (46%) were indeterminate; 112/152 indeterminate tests (74%) occurred because of failure to achieve target heart rate (HR) due to chronotropic incompetence or physical limitations. There were differences in patient characteristics according to MTWA result. Independent predictors of a negative result included younger age and higher left ventricular ejection fraction (LVEF). Independent predictors of a positive result included higher HR during MTWA testing and lower LVEF. Independent predictors of an indeterminate result included older age and history of previous/paroxysmal AF. CONCLUSIONS: Only half of patients with HF are eligible for MTWA testing and the most common result is an indeterminate test. Patients with positive and indeterminate tests have different clinical characteristics. MTWA treadmill testing is not widely applicable in typical HF patients and is unlikely to refine risk stratification for sudden death on a population level.

The inverse relationship between alanine aminotransferase in the normal range and adverse cardiovascular and non-cardiovascular outcomes.

BACKGROUND: High serum alanine aminotransferase (ALT) levels have been associated with increased risk of diabetes and with increased mortality, but associations of variations of ALT in the normal range with outcomes have been less well studied. METHODS: We studied the relationship between ALT, mortality and cardiovascular events in the West of Scotland Coronary Prevention Study (WOSCOPS) and the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trials that explicitly excluded subjects with clinically significant liver damage, plus the Leiden 85-plus, a study of survivors to age 85 years. The associations between ALT and morbidity and mortality outcomes were investigated using Cox proportional hazard models adjusting for a comprehensive panel of cardiovascular risk factors. RESULTS: In all three study cohorts, ALT displayed an independent inverse relationship with all-cause mortality so that hazard ratios for fourth versus first quarter of ALT were all below 1.0; HRs 0.64 [95% confidence interval (CI) 0.50-0.81], 0.86 (0.73-1.01), 0.66 (0.50-0.87); WOSCOPS, PROSPER, Leiden 85-plus, respectively. In WOSCOPS and PROSPER, ALT was also inversely associated with risk of fatal plus non-fatal cardiovascular events, including coronary heart disease (CHD) events and stroke. CONCLUSIONS: In three independent populations, ALT in the normal range displayed an inverse relationship with total mortality, cardiovascular events and non-cardiovascular events in middle-to-older aged subjects without evidence of clinically significant liver damage, independent of traditional cardiovascular and other risk factors. These findings indicate that the relationship between ALT and clinical outcomes is more complex than generally appreciated.

Slowing of Electrical Activity in Ventricular Fibrillation is Not Associated with Increased Defibrillation Energies in the Isolated Rabbit Heart.

Prolonged out-of-hospital ventricular fibrillation (VF) arrests are associated with reduced ECG dominant frequency (DF) and diminished defibrillation success. Partial reversal of ischemia increases ECG DF and improves defibrillation outcome. We have investigated the metabolic components of ischemia responsible for the decline in ECG DF and defibrillation success. Isolated Langendorff-perfused rabbit hearts were loaded with the voltage-sensitive dye RH237. Using a photodiode array, epicardial membrane potentials were recorded at 252 sites (15 mm × 15 mm) on the anterior surface of the left and right ventricles. Simultaneously, a global ECG was recorded. VF was induced by burst pacing, and after 60s, perfusion was either reduced to 6 ml/min or the perfusate composition changed to impose hypoxia (95% N(2)/5% CO(2)), pH 6.7 (80% O(2)/20% CO(2)), or hyperkalemia (8 mM). Using fast Fourier transform, power spectra were created from the optical signals and the global ECG. The optical power spectra were summated to give a global power spectrum (pseudoECG). At 600 s the minimum defibrillation voltage (MDV) was determined by step-up protocol. During VF, the ECG and pseudoECG DF were reduced by low-flow ischemia (9.0 ± 1.0 Hz, p < 0.01, n = 5) and raised [K(+)](o) (12.2 ± 1.3 Hz, p < 0.05, n = 7) compared to control (19.2 ± 1.5 Hz, n = 20), but were unaffected by acidic pH(o) (16.7 ± 1.1 Hz, n = 11) and hypoxia (14.0 ± 1.2 Hz, n = 10). In contrast, the MDV was raised by acidic pH (156.1 ± 26.4 V, p < 0.001) and hypoxia (154.1 ± 22.1 V, p < 0.01) compared to control (65.6 ± 2.3 V), but comparable changes were not observed in low-flow ischemia (61.0 ± 0.5 V) or raised [K(+)](o) (56 ± 3 V). In summary, different metabolites are responsible for the reduction in DF and the increase in defibrillation energy during ischemic VF.

Obesity is associated with fatal coronary heart disease independently of traditional risk factors and deprivation.

BACKGROUND: The effect of body mass index (BMI) on coronary heart disease (CHD) risk is attenuated when mediators of this risk (such as diabetes, hypertension and hyperlipidaemia) are accounted for. However, there is now evidence of a differential effect of risk factors on fatal and non-fatal CHD events, with markers of inflammation more strongly associated with fatal than non-fatal events. OBJECTIVE: To describe the association with BMI separately for both fatal and non-fatal CHD risk after accounting for classical risk factors and to assess any independent effects of obesity on CHD risk. METHODS AND RESULTS: In the West of Scotland Coronary Prevention Study BMI in 6082 men (mean age 55 years) with hypercholesterolaemia, but no history of diabetes or CVD, was related to the risk of fatal and non-fatal CHD events. After excluding participants with any event in the first 2 years, 1027 non-fatal and 214 fatal CHD events occurred during 14.7 years of follow-up. A minimally adjusted model (age, sex, statin treatment) and a maximally adjusted model (including known CVD risk factors and deprivation) were compared, with BMI 25-27.4 kg/m² as referent. The risk of non-fatal events was similar across all BMI categories in both models. The risk of fatal CHD events was increased in men with BMI 30.0-39.9 kg/m² in both the minimally adjusted model (HR = 1.75 (95% CI 1.12 to 2.74)) and the maximally adjusted model (HR = 1.60 (95% CI 1.02 to 2.53)). CONCLUSIONS: These hypothesis generating data suggest that obesity is associated with fatal, but not non-fatal, CHD after accounting for known cardiovascular risk factors and deprivation. Clinical trial registration WOSCOPS was carried out and completed before the requirement for clinical trial registration.

Alternans of action potential duration and amplitude in rabbits with left ventricular dysfunction following myocardial infarction.

T-wave alternans may predict the occurrence of ventricular arrhythmias in patients with left ventricular dysfunction and experimental work has linked discordant repolarization alternans to the induction of re-entry. The aim of this study was to examine the occurrence of transmural repolarization alternans and to investigate the link between alternans and ventricular arrhythmia in rabbits with left ventricular dysfunction following myocardial infarction. Optical mapping was used to record action potentials from the transmural surface of left ventricular wedge preparations from normal and post-infarction hearts during a progressive reduction in pacing cycle length at 30 and 37°C. Data were analyzed using custom software, including spectral analysis. There were no significant differences in baseline transmural electrophysiology between the groups. Post-infarction hearts had a lower threshold for both repolarization alternans (286 vs. 333 bpm, p<0.05) and ventricular arrhythmias (79 vs. 19%, p<0.01) during rapid pacing, which was not accounted for by increased transmural discordant alternans. In VF-prone hearts, alternans in optical action potential amplitude was observed and increased until 2:1 block occurred. The degree of optical action potential amplitude alternans (12.0 ± 7.0 vs. 1.8 ± 0.3, p<0.05), but not APD(90) alternans (1.4 ± 0.6 vs. 1.1 ± 0.1, p>0.05) was associated with VF inducibility during rapid pacing. Post-infarction hearts are more vulnerable to transmural alternans and ventricular arrhythmias at rapid rates. Alternans in optical action potential amplitude was associated with conduction block and VF. The data suggest that changes in optical action potential amplitude may underlie a mechanism for alternans-associated ventricular arrhythmia in left ventricular dysfunction.

Microvolt T-wave alternans in end-stage renal disease patients--associations with uremic cardiomyopathy.

BACKGROUND AND OBJECTIVES: Premature cardiovascular (CV) events, especially sudden cardiac death, are common in ESRD patients and associated with uremic cardiomyopathy. Identification of high-risk patients is difficult. Microvolt T-wave alternans (MTWA) is a noninvasive method of detecting variability in electrocardiogram (ECG) T-wave morphology and is a promising technique for identifying patients at high risk of ventricular tachyarrhythmias. MTWA results of ESRD and hypertensive left ventricular hypertrophy (LVH) patients were assessed to determine the prevalence of abnormal results and associations with uremic cardiomyopathy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this single-center observational study, 200 ESRD and 30 LVH patients underwent assessment including CV history, ECG, cardiac magnetic resonance imaging, and an MTWA exercise test. MTWA results were classified as "negative" or "abnormal" on the basis of previously published reports. RESULTS: An abnormal MTWA result was more common in ESRD compared with LVH patients (57.5% versus 26.7%, respectively; P = 0.002). In ESRD patients, MTWA was significantly associated with uremic cardiomyopathy, clinical history of atherosclerosis (coronary, cerebral, peripheral) and diabetes mellitus, older age, and hemodialysis therapy. Independent associations with an abnormal MTWA result were older age, macrovascular disease, increased left ventricle (LV) mass, and LV dilation. CONCLUSIONS: Features of uremic cardiomyopathy are associated with an abnormal MTWA result.

Effect of activation sequence on transmural patterns of repolarization and action potential duration in rabbit ventricular myocardium.

Although transmural heterogeneity of action potential duration (APD) is established in single cells isolated from different tissue layers, the extent to which it produces transmural gradients of repolarization in electrotonically coupled ventricular myocardium remains controversial. The purpose of this study was to examine the relative contribution of intrinsic cellular gradients of APD and electrotonic influences to transmural repolarization in rabbit ventricular myocardium. Transmural optical mapping was performed in left ventricular wedge preparations from eight rabbits. Transmural patterns of activation, repolarization, and APD were recorded during endocardial and epicardial stimulation. Experimental results were compared with modeled data during variations in electrotonic coupling. A transmural gradient of APD was evident during endocardial stimulation, which reflected differences previously seen in isolated cells, with the longest APD at the endocardium and the shortest at the epicardium (endo: 165 ± 5 vs. epi: 147 ± 4 ms; P < 0.05). During epicardial stimulation, this gradient reversed (epi: 162 ± 4 vs. endo: 148 ± 6 ms; P < 0.05). In both activation sequences, transmural repolarization followed activation and APD shortened along the activation path such that significant transmural gradients of repolarization did not occur. This correlation between transmural activation time and APD was recapitulated in simulations and varied with changes in intercellular coupling, confirming that it is mediated by electrotonic current flow between cells. These data suggest that electrotonic influences are important in determining the transmural repolarization sequence in rabbit ventricular myocardium and that they are sufficient to overcome intrinsic differences in the electrophysiological properties of the cells across the ventricular wall.

EHRA Expert Consensus Statement on the management of cardiovascular implantable electronic devices in patients nearing end of life or requesting withdrawal of therapy.

The purpose of this Consensus Statement is to focus on implantable cardioverter-defibrillator (ICD) deactivation in patients with irreversible or terminal illness. This statement summarizes the opinions of the Task Force members, convened by the European Heart Rhythm Association (EHRA) and the Heart Rhythm Society (HRS), based on ethical and legal principles, as well as their own clinical, scientific, and technical experience. It is directed to all healthcare professionals who treat patients with implanted ICDs, nearing end of life, in order to improve the patient dying process. This statement is not intended to recommend or promote device deactivation. Rather, the ultimate judgement regarding this procedure must be made by the patient (or in special conditions by his/her legal representative) after careful communication about the deactivation's consequences, respecting his/her autonomy and clarifying that he/she has a legal and ethical right to refuse it. Obviously, the physician asked to deactivate the ICD and the industry representative asked to assist can conscientiously object to and refuse to perform device deactivation.

Fasting plasma glucose in non-diabetic participants and the risk for incident cardiovascular events, diabetes, and mortality: results from WOSCOPS 15-year follow-up.

AIMS: The evidence base for fasting plasma glucose (FPG) in the non-diabetic range as a risk factor for cardiovascular disease (CVD) is inconclusive. We investigated this question in the West of Scotland Coronary Prevention Study (WOSCOPS). METHODS AND RESULTS: In WOSCOPS, we related FPG in 6447 men (mean age 55 years) with hypercholesterolaemia, but no history of CVD or diabetes, to the risk of cardiovascular events and mortality over 14.7 years of follow-up; 2381 non-fatal/fatal cardiovascular events and 1244 deaths occurred. Participants were divided into fifths of baseline FPG, Q1 (< or =4.3 mmol/L) to Q5 (>5.1-6.9 mmol/L). Q2 was designated the referent based on previous studies which have suggested a J-shaped relationship between FPG and CVD. Compared with Q2 (>4.3-4.6 mmol/L), men in Q5 had no elevated risk for cardiovascular events [hazard ratio (HR) 0.95 (0.83-1.08)], or all-cause mortality [HR 0.96 (0.80-1.15)] in fully adjusted analyses despite a significant risk for incident diabetes [HR 22.05 (10.75-45.22)]. After further dividing Q5 into fifths, Q5a-e, individuals in Q5e (FPG 5.8-6.9 mmol/L) were also not at increased risk of cardiovascular events [HR 1.05 (0.82-1.35)] or other endpoints compared with Q2. All results were similar using Q1 as the referent. CONCLUSION: Elevations in FPG in the non-diabetic range were not associated with long-term risk of cardiovascular events in middle-aged men in WOSCOPS. These data suggest that the current FPG cutoff for diagnosing diabetes also appropriately identifies western men at risk of CVD.

I-123 MIBG cardiac uptake measurements: limitations of collimator choice and scatter correction in the clinical context.

OBJECTIVE: Low uptake of metaiodobenzylguanidine (MIBG) in patients with heart failure generally indicates poor prognosis. Our objective was to determine the best method for calculating I-123 MIBG uptake. MIBG uptake as a percentage of the injected dose is presented as an alternative method for serial assessment. METHODS: Patients with chronic heart failure were imaged with I-123 MIBG with both a medium-energy (ME) collimator and a low-energy high-sensitivity (LEHS) collimator. Scatter correction was used to correct the LEHS images. Heart-to-mediastinal (H/M) ratio and the percentage of myocardial uptake of MIBG were obtained. RESULTS: Mean H/M ratios for the ME images, LEHS images and scatter-corrected LEHS images were 2.45+/-0.61, 2.22+/-0.47 and 2.51+/-0.62, respectively. Mean H/M ratio was significantly different among all the three sets (P<0.001) of images. The average difference in H/M ratios between the ME images and LEHS images was lower when scatter correction was applied (4.95% vs. 9.79%). The error in calculating the myocardial uptake as a percentage of the injected dose was significantly lower than the error in calculating H/M ratio (0.2 vs.10.2% LEHS; 0.3 vs.16.0% ME; 0.2 vs.11.8% LEHS scatter corrected). CONCLUSION: For quantitative assessment of H/M ratio in I-123 MIBG imaging a LEHS collimator can be used in place of a ME collimator to achieve better counting statistics, but scatter correction must be used. The calculation of the myocardial uptake as a percentage of the injected dose has potential as an alternative method of measurement, particularly for serial assessment.

Low serum cortisol predicts early death after acute myocardial infarction.

OBJECTIVE: To determine whether low serum cortisol concentrations are associated with adverse prognosis in patients with acute myocardial infarction. Low serum cortisol concentrations have been associated with adverse prognosis in critical illness of diverse etiology. DESIGN: Nested case-control study. SETTING: Prospective cohort study of consecutive patients admitted with acute myocardial infarction to nine Scottish hospitals. PATIENTS: A total of 100 patients who survived 30 days (controls) and 100 patients who died within 30 days (cases). MEASUREMENTS AND MAIN RESULTS: Admission cortisol concentrations were lower in patients who died than those who survived (median, 1189 nmol/L vs. 1355 nmol/L; p < .001). A cortisol concentration in the bottom quartile (<1136 nmol/L) was a strong predictor of death within 30 days and remained so after adjustment for age and cardiac troponin concentration (adjusted odds ratio, 8.78; 95% confidence interval, 3.09-24.96; p < .001). CONCLUSIONS: Patients who mount a lesser cortisol stress response to acute myocardial infarction have a poorer early prognosis.

Isoprenaline increases the slopes of restitution trajectory in the conscious rabbit with ischemic heart failure.

Roughly speaking, restitution is the dependence of recovery time of cardiac electrical activity on heart rate. Increased restitution slope is theorized to be predictive of sudden death after heart injury such as from coronary artery occlusion (ischemia). Adrenaline analogs are known to increase restitution slope in normal hearts, but their effects in failing hearts are unknown. Twenty-six rabbits underwent coronary ligation (n = 15) or sham surgery (n = 11) and implantation of a lead in the heart for recording electrocardiograms. Eight weeks later, unanesthetized rabbits were given 0.25-2.0 ml of 1 µmol/L isoprenaline intravenously, which increased heart rate. Heart rate was quantified by time between QRS peaks (RR) and heart activity duration by R to T peak time (QTp). Ligated rabbits (n = 6) had lower ejection fraction than sham rabbits (n = 7, p < 0.0001) indicative of heart failure, but similar baseline RR (269 ± 15 vs 292 ± 23 ms, p = 0.07), QTp (104 ± 17 vs 91 ± 9 ms, p = 0.1), and isoprenaline-induced minimum RR (204 ± 11 vs 208 ± 6 ms, p = 0.4). The trajectory of QTp vs TQ plots displayed hysteresis and regions of negative slope. The slope of the positive slope region was >1 in ligated rabbits (1.27 ± 0.66) and <1 in sham rabbits (0.35 ± 0.14, p = 0.004). The absolute value of the negative slope was greater in ligated rabbits (- 0.81 ± 0.52 vs - 0.35 ± 0.14, p = 0.04). Isoprenaline increased heart rate and slopes of restitution trajectory in failing hearts. The dynamics of restitution trajectory may hold clues for sudden death in heart failure patients.

Paroxysmal bidirectional ventricular tachycardia with tachycardiomyopathy in a pregnant woman.

Palpitations in pregnancy are not an uncommon complaint. We present a case of palpitations in the third trimester related to bidirectional ventricular tachycardia with evidence, of left ventricular systolic dysfunction. The case was successfully managed with flecainide therapy and urgent elective caesarean section. The rhythm stabilised to sinus rhythm and left ventricular systolic function normalised. We discuss the possible underlying diagnosis of catecholaminergic polymorphic ventricular tachycardia with resultant tachycardiomyopathy. A literature review of bidirectional ventricular tachycardia is presented. This is the first reported case of bidirectional VT producing LV systolic dysfunction, which normalised following stabilisation of rhythm. The complex issues of management of this case in particular with regard to the pregnancy are discussed.