Cardiotoxicity Following Cancer Treatment.

More than half of those born after 1960 will develop cancer during their lifetime. Fortunately, owing to improved diagnosis and treatment, cure rates have risen steadily over the last three decades. With an increased survivorship, more will experience adverse effects of cancer therapeutics on the heart. As the oncologist's focus begins to encompass the issues of cancer survivorship, awareness of the management of cardiac toxicity would be prudent for all physicians looking after patients with cancer.

The cost-effectiveness of cardiac computed tomography for patients with stable chest pain.

OBJECTIVE: To assess the cost-effectiveness of cardiac CT compared with exercise stress testing (EST) in improving the health-related quality of life of patients with stable chest pain. METHODS: A cost-utility analysis alongside a single-centre randomised controlled trial carried out in Northern Ireland. Patients with stable chest pain were randomised to undergo either cardiac CT assessment or EST (standard care). The main outcome measure was cost per quality adjusted life year (QALY) gained at 1 year. RESULTS: Of the 500 patients recruited, 250 were randomised to cardiac CT and 250 were randomised to EST. Cardiac CT was the dominant strategy as it was both less costly (incremental total costs -£50.45; 95% CI -£672.26 to £571.36) and more effective (incremental QALYs 0.02; 95% CI -0.02 to 0.05) than EST. At a willingness-to-pay threshold of £20 000 per QALY the probability of cardiac CT being cost-effective was 83%. Subgroup analyses indicated that cardiac CT appears to be most cost-effective in patients with a likelihood of coronary artery disease (CAD) of <30%, followed by 30%-60% and then >60%. CONCLUSIONS: Cardiac CT is cost-effective compared with EST and cost-effectiveness was observed to vary with likelihood of CAD. This finding could have major implications for how patients with chest pain in the UK are assessed, however it would need to be validated in other healthcare systems. TRIAL REGISTRATION NUMBER: (ISRCTN52480460); results.

A comparison of cardiac computerized tomography and exercise stress electrocardiogram test for the investigation of stable chest pain: the clinical results of the CAPP randomized prospective trial.

AIMS: To determine the symptomatic and prognostic differences resulting from a novel diagnostic pathway based on cardiac computerized tomography (CT) compared with the traditional exercise stress electrocardiography test (EST) in stable chest pain patients. METHODS AND RESULTS: A prospective randomized controlled trial compared selected patient outcomes in EST and cardiac CT coronary angiography groups. Five hundred patients with troponin-negative stable chest pain and without known coronary artery disease were recruited. Patients completed the Seattle Angina Questionnaires (SAQ) at baseline, 3, and 12 months to assess angina symptoms. Patients were also followed for management strategies and clinical events. Over the year 12 patients withdrew, resulting in 245 in the EST cohort and 243 in the CT cohort. There was no significant difference in baseline demographics. The CT arm had a statistical difference in angina stability and quality-of-life domains of the SAQ at 3 and12 months, suggesting less angina compared with the EST arm. In the CT arm, there was more significant disease identified and more revascularizations. Significantly, more inconclusive results were seen in the EST arm with a higher number of additional investigations ordered. There was also a longer mean time to management. There were no differences in major adverse cardiac events between the cohorts. At 1 year in the EST arm, there were more Accident and Emergency (A&E) attendances and cardiac admission. CONCLUSION: Cardiac CT as an index investigation for stable chest pain improved angina symptoms and resulted in fewer investigations and re-hospitalizations compared with EST. CLINICAL TRIAL REGISTRATION: http://www.controlled-trials.com/ISRCTN52480460.

Multimodal functional and anatomic imaging identifies preclinical microvascular abnormalities in type 1 diabetes mellitus.

Structural and functional changes in the microcirculation in type 1 diabetes mellitus predict future end-organ damage and macrovascular events. We explored the utility of novel signal processing techniques to detect and track changes in ocular hemodynamics in patients with this disease. Twenty-four patients with uncomplicated type 1 diabetes mellitus and eighteen age- and sex-matched control subjects were studied. Doppler ultrasound was used to interrogate the carotid and ophthalmic arteries, and digital photography was used to image the retinal vasculature. Frequency analysis algorithms were applied to quantify velocity waveform structure and retinal photographic data at baseline and after inhalation of 100% O2. Frequency data were compared between groups. No significant differences were found in the resistive index between groups at baseline or after inhaled O2. Frequency analysis of Doppler flow velocity waveforms identified significant differences in bands 3-7 between patients and control subjects in data captured from the ophthalmic artery (P < 0.01 for each band). In response to inhaled O2, changes in frequency band amplitudes were significantly greater in control subjects compared with patients (P < 0.05). Only control subjects demonstrated a positive correlation (R = 0.61) between changes in retinal vessel diameter and frequency band amplitudes derived from ophthalmic artery waveform data. The use of multimodal signal processing techniques applied to Doppler flow velocity waveforms and retinal photographic data identified preclinical changes in the ocular microcirculation in patients with uncomplicated diabetes mellitus. An impaired autoregulatory response of the retinal microvasculature may contribute to the future development of retinopathy in such patients.

Pre-hospital body surface potential mapping improves early diagnosis of acute coronary artery occlusion in patients with ventricular fibrillation and cardiac arrest.

AIMS: To determine whether 80-lead body surface potential mapping (BSPM) improves detection of acute coronary artery occlusion in patients presenting with out-of-hospital cardiac arrest (OHCA) due to ventricular fibrillation (VF) and who survived to reach hospital. METHODS AND RESULTS: Of 645 consecutive patients with OHCA who were attended by the mobile coronary care unit, VF was the initial rhythm in 168 patients. Eighty patients survived initial resuscitation, 59 of these having had BSPM and 12-lead ECG post-return of spontaneous circulation (ROSC) and in 35 patients (age 69±13 yrs; 60% male) coronary angiography performed within 24 h post-ROSC. Of these, 26 (74%) patients had an acutely occluded coronary artery (TIMI flow grade [TFG] 0/1) at angiography. Twelve-lead ECG criteria showed ST-segment elevation (STE) myocardial infarction (STEMI) using Minnesota 9-2 criteria--sensitivity 19%, specificity 100%; ST-segment depression (STD) ≥0.05 mV in ≥2 contiguous leads--sensitivity 23%, specificity 89%; and, combination of STEMI or STD criteria--sensitivity 46%, specificity 100%. BSPM STE occurred in 23 (66%) patients. For the diagnosis of TFG 0/1 in a main coronary artery, BSPM STE had sensitivity 88% and specificity 100% (c-statistic 0.94), with STE occurring most commonly in either the posterior, right ventricular or high right anterior territories. CONCLUSION: Among OHCA patients presenting with VF and who survived resuscitation to reach hospital, post-resuscitation BSPM STE identifies acute coronary occlusion with sensitivity 88% and specificity 100% (c-statistic 0.94).

Improved detection of acute myocardial infarction in patients with chest pain and significant left main stem coronary stenosis.

BACKGROUND: Non-invasive diagnosis of acute myocardial infarction (AMI) associated with significant left main stem (LMS) stenosis remains challenging. METHODS: Consecutive patients presenting with acute ischaemic-type chest pain from 2000 to 2010 were analysed. Entry criteria: 12-lead ECG and Body Surface Potential Map (BSPM) at presentation, cardiac troponin T (cTnT) ≥12 h and coronary angiography during admission. cTnT ≥0.03 µg/l defined AMI. ECG abnormalities assessed: STEMI by Minnesota criteria; ST elevation (STE) aVR ≥0.5 mm; ST depression (STD) ≥0.5 mm in ≥2 contiguous leads (CL); T-wave inversion (TWI) ≥1 mm in ≥2 CL. BSPM STE was ≥2 mm in anterior, ≥1 mm in lateral, inferior, right ventricular or high right anterior and ≥0.5 mm in posterior territories. Significant LMS stenosis was ≥70%. RESULTS: Enrolled were 2810 patients (aged 60 ± 12 years; 71% male). Of these, 116 (4.1%) had significant LMS stenosis with AMI occurring in 92 (79%). STEMI by Minnesota criteria occurred in 13 (11%) (sensitivity 12%, specificity 92%), STE in lead aVR in 23 (20%) (sensitivity 23%, specificity 92%), TWI in 38 (33%) (sensitivity 34%, specificity 71%) and STD in 51 (44%) (sensitivity 49%, specificity 75%). BSPM STE occurred in 85 (73%): sensitivity 88%, specificity 83%, positive predictive value 95% and negative predictive value 65%. Of those with AMI, 74% had STE in either the high right anterior or right ventricular territories not identified by the 12-lead ECG. C-Statistic for AMI diagnosis using BSPM STE was 0.800 (P < 0.001). CONCLUSION: In patients with significant LMS stenosis presenting with chest pain, BSPM STE has improved sensitivity (88%), with specificity 83%, over 12-lead ECG in the diagnosis of AMI.

Flow-mediated dilatation of the brachial artery is a poorly reproducible indicator of microvascular function in Type I diabetes mellitus.

BACKGROUND: Flow-mediated dilatation (FMD) of the brachial artery is commonly measured as a surrogate marker of endothelial function. Its measurement is, however, technically demanding and reports regarding its reproducibility have not always been favourable. AIM: Two Type I diabetes and control group comparator studies were conducted to assess the reproducibility of FMD and to analyse blood flow data normally discarded during FMD measurement. DESIGN: The studies were sequential and differed only with regard to operator and ultrasound machine. Seventy-two subjects with diabetes and 71 controls were studied in total. METHODS: Subjects had FMD measured conventionally. Blood velocity waveforms were averaged over 10 pulses post forearm ischaemia and their component frequencies analysed using the wavelet transform, a mathematical tool for waveform analysis. The component frequencies were grouped into 11 bands to facilitate analysis. RESULTS: Subjects were well-matched between studies. In Study 1, FMD was significantly impaired in subjects with Type I diabetes vs. controls (median 4.35%, interquartile range 3.10-4.80 vs. 6.50, 4.79-9.42, P < 0.001). No differences were detected between groups in Study 2, however. However, analysis of blood velocity waveforms yielded significant differences between groups in two frequency bands in each study. CONCLUSION: This report highlights concerns over the reproducibility of FMD measures. Further work is required to fully elucidate the role of analysing velocity waveforms after forearm ischaemia.

Constriction infection.

Chronic constrictive pericarditis (CCP) is a clinical syndrome caused by compression of the heart due to a thickened or rigid pericardium. In the affluent West, the majority of cases of CCP are neither tuberculous nor calcific. In an American cohort undergoing pericardectomy for the condition, only 27% had calcification and under 10% had TB [1]. As a result, pericardial calcification (PC) as a marker of CCP has become neglected. We present a 48-year-old male admitted with atrial flutter, acute chest infection and signs of right heart congestion. PC was documented one year previously on a non-contrast CT chest. On this occasion, cardiac catheterisation confirmed hemodynamically significant CCP and cardiac magnetic resonance (cMR) study showed contiguous mass lesions in the pericardium, compression of the right ventricle, enlargement of the right atrium, hepatic enlargement and a pneumonic process in the left lung. He was commenced on antibiotics and anti-tuberculous therapy with a diagnosis of bacterial super-infection of tuberculous CCP. This was confirmed at pericardectomy along with an infected fistula into the left lung. Any finding of PC should be followed up with a thorough haemodynamic and anatomical assessment using any of a wide range of non-invasive imaging modalities.

Elevated CA 125 and ascites: not always malignancy.

BACKGROUND: We present two clinical cases from a single institution where a final diagnosis of cardiac failure was made following the initial finding of ascites and an elevated CA 125 level. In both cases gynaecological malignancy was initially suspected. METHODS: Following negative confirmatory tests for gynaecological malignancy, echocardiography was undertaken. RESULTS: Patient 1 had severe right ventricular dilatation and dysfunction. Patient 2 had biventricular dysfunction with pulmonary hypertension. Both patients responded to standard therapy for heart failure, including loop diuretics.

Waveform optimization for internal atrial defibrillation: effects of waveform rounding, phase duration, and voltage swing.

The aim of this study was to compare the efficacy of internal atrial defibrillation by conventional truncated exponential biphasic waveforms with and without waveform rounding (1-2 phases) and to determine optimal duration for this novel double rounded waveform. Atrial fibrillation, induced by rapid electrical stimulation, was converted by internal shocks through defibrillation catheters (lateral right atrium and coronary sinus) in anesthetised sheep. Rounding the leading edges of the conventional biphasic waveform (Ventritex HVS-02; settings 100/-50 V, 150/-70 V, and 200/-100 V; n = 8) reduced delivered peak and trough voltages, currents, and energy (by > or = 21 %, P < 0.001; for double (both phases) rounded) without decreasing cardioversion success. At 100/-50 V the efficacy of single (first phase) rounded (53 +/- 13%; mean +/- SEM) and double rounded (59 +/- 11%) shocks was similar to the conventional waveform (56 +/- 14%). Double rounded waveform (phase durations 1-20 ms) efficacy was optimum at 6-10 ms phase duration (100% success at 10-ms phase duration; 1.52 +/- 0.04 J delivered energy; n = 6). Successful cardioversion by conventional, single rounded, and double rounded biphasic waveforms (duration 6 ms each phase), conventional monophasic, rounded monophasic (duration 12 ms), and a damped sine waveform correlated strongly with peak-to-trough voltage swing within the waveform (r = 0.882; P < 0.01; n = 8). For internal atrial defibrillation, rounding both phases of the conventional biphasic waveforms, the double rounded waveform, permits similar efficacy to the conventional truncated exponential biphasic waveform at reduced peak voltage, current, and delivered energy. Optimum phase duration is 6-10 ms (tested range 1-20 ms).

The effects of potassium-ATP channel modulation on ventricular fibrillation and defibrillation in the pig heart.

BACKGROUND: Drugs acting on the cardiac ATP-sensitive potassium (K-ATP) channels may modulate responses to ischaemia and arrhythmogenesis. We investigated the effects of K-ATP channel modulation on frequency patterns of ventricular fibrillation (VF) and on defibrillation threshold (DFT). METHODS AND RESULTS: Each group of 24 pigs randomly received intravenous levcromakalim (LKM) 40 microgram/kg (K-ATP agonist), glibenclamide (Glib) 20 mg/kg (K-ATP antagonist), saline or vehicle. Firstly, QTc interval was measured before and after drug. VF was then induced by endocardial stimulation and its power spectra and dominant frequencies over 15 min determined by fast Fourier transformation. Secondly, transthoracic DFT was determined (step-up/step-down protocol) before and after each drug. LKM reduced QTc interval (e.g., lead II, 354-321 ms, P<0.05) and increased the dominant VF frequency between 6 and 8 min (9.5+/-0.5 Hz at 6.5 min compared with 7.2+/-0.6 Hz (saline), 7.4+/-0.8 Hz (vehicle), 6.8+/-0.5 Hz (Glib), P=0.03). LKM reduced (to 57.2+/-2.1 mmHg) and Glib increased (to 107.8+/-6.1) mean arterial BP compared with saline (80.3+/-5.6) and vehicle (87. 6+/-7.1; P<0.01). There was no significant difference in defibrillation threshold energy, current or voltage, after any drug. CONCLUSIONS: Activation of K-ATP channels reduced blood pressure and QTc interval. The lack of major effect on VF dominant frequency and DFT of either LKM or Glib suggests that prior administration of similar drugs to patients should not prejudice outcome from VF cardiac arrest.

Randomised comparison of electrode positions for cardioversion of atrial fibrillation.

OBJECTIVE: To compare the relative efficacy of anteroanterior v anteroposterior electrode pad positions for external cardioversion of atrial fibrillation. DESIGN: Prospective randomised trial. SETTING: Tertiary referral cardiology centre in the United Kingdom. PATIENTS: 90 patients undergoing elective cardioversion for atrial fibrillation. INTERVENTIONS: Cardioversion was attempted with self adhesive electrode pads with an area of 106 cm2 placed either in the anteroanterior (AA) or anteroposterior (AP) positions. Initial shock was 100 J which, if unsuccessful, was followed by 200 J, 300 J, and 360 J if required. Peak current and transthoracic impedance were measured. MAIN OUTCOME MEASURES: Cardioversion success rate and energy requirements. RESULTS: Cardioversion was successful in 81% of the patients (73/90). There was no statistically significant difference in the cardioversion success rate (AA 84%, 38/45 patients; AP 78%, 35/45 patients; p = 0.42) or mean (SD) energy requirement for all patients (AA 223 (96.1) J; AP 232 (110) J) or for patients who were successfully cardioverted (AA 197.9 (82.4) J; AP 195.4 (97.2) J; p = 0.9) between the two pad positions. The mean transthoracic impedance (TTI) for the first shock (AA 77.5 (18.4) ohms; AP 73.7 (18.7) ohms; p = 0.34) was not significantly different between the two groups. TTI correlated significantly with body mass index, percentage body fat, and chest AP diameter. There was a progressive decrease in TTI with serial shocks. While aetiology and TTI were the two independent significant predictive factors for energy requirement, duration of atrial fibrillation was the only independent predictor of cardioversion success in a multivariate analysis. CONCLUSIONS: Electrode pad position is not a determinant of cardioversion success rate or energy requirement.

Periprocedural creatine kinase-MB elevations: long-term impact and clinical implications.

Since the introduction of percutaneous transluminal coronary angioplasty (PTCA), percutaneous intervention with balloon catheters, stents, and atherectomy devices has become a widely accepted practice. The persistent complication of non-Q-wave myocardial infarction (MI), as evidenced by increased cardiac enzyme levels after intervention, has aroused only moderate concern because its incidence was perceived to be small and not clinically relevant. With more systematic assessments of cardiac enzymes--specifically, creatine kinase (CK) and its MB isoform--evidence has begun to clarify both the incidence and the prognosis of periprocedural non-Q-wave MI: It appears to occur nearly three times more often than is clinically evident across all device types (8 to 9% of all interventions) and is directly and continuously associated with adverse outcomes, including late death. Although directional and rotational atherectomy improve angiographic outcome compared with PTCA, periprocedural infarction occurs at least twice as often with these newer technologies; the incidence associated with stent placement is comparable to and possibly higher than that of PTCA. Factors that may cause elevated CK-MB levels include distal embolization, side branch occlusion, thrombus, and coronary spasm. Analyses of the major trials of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors, a class of potent antiplatelet agents, show striking effectiveness of these drugs in reducing the incidence of "enzyme-only" or "silent" MI and in improving long-term clinical outcomes. The findings implicate platelet mediation in the occurrence of periprocedural infarction and suggest an important role for antiplatelet therapy, particularly GP IIb/IIIa receptor inhibition, in protecting patients undergoing percutaneous intervention.

Rounded biphasic waveform reduces energy requirements for transvenous catheter cardioversion of atrial fibrillation and flutter.

We postulated that reducing peak leading edge shock voltage and its rate of rise (waveform rounding) would reduce energy requirements for cardioversion of AF and AFl, and may therefore reduce patient discomfort. Transvenous defibrillating catheters (In-Control Inc.) were placed in the RAA (active fixation) and the CS of six anesthetized sheep. AF or AFl was induced by electrical stimulation (100 Hz, 2 V; Grass stimulator). A standard trapezoidal biphasic (S) waveform (3-ms duration each phase) was compared with a similar waveform that had the first phase rounded (R). Cardioversion was attempted after 30 seconds of arrhythmia, using a Ventritex HVS-O2 defibrillator modified to allow waveform rounding. Each waveform was randomly tested several times at 100-, 150-, and 200-V leading edges, and percentage cardioversion success calculated. Shock energy was calculated from delivered current and voltage using Flukeview (Fluke, Inc.) software. At 100-V leading edge R (64% success) and S (59%), shocks were similarly efficacious (P = 0.37). However, R delivered less current, voltage, and energy than the comparable S shock (means 1.30 A, 65.0 V, 0.33 J R vs 1.92 A, 94.2 V, 0.47 J S; P = 0.0001). Both waveforms were equally successful at 150 V (88% vs 100%; P = NS) and 200 V (100% vs 100%), but again R delivered less current, voltage, and energy (2.05 A, 102.5 V, 0.82 J R vs 2.78 A, 142.3 V, 1.11 J S at 150 V; 2.76 A, 141.2 V, 1.58 J R vs 3.77 A, 189.4 V, 2.03 J S at 200 V; both P = 0.0001). No arrhythmic or other complications occurred in the 174 shocks delivered. Waveform rounding reduces delivered peak voltage, current, and energy without reducing defibrillation efficacy. To determine if these changes are associated with a reduction in discomfort, patients with AF are currently being cardioverted with these waveforms during electrophysiological studies.