Feasibility of cardiovascular magnetic resonance derived coronary wave intensity analysis.

BACKGROUND: Wave intensity analysis (WIA) of the coronary arteries allows description of the predominant mechanisms influencing coronary flow over the cardiac cycle. The data are traditionally derived from pressure and velocity changes measured invasively in the coronary artery. Cardiovascular magnetic resonance (CMR) allows measurement of coronary velocities using phase velocity mapping and derivation of central aortic pressure from aortic distension. We assessed the feasibility of WIA of the coronary arteries using CMR and compared this to invasive data. METHODS: CMR scans were undertaken in a serial cohort of patients who had undergone invasive WIA. Velocity maps were acquired in the proximal left anterior descending and proximal right coronary artery using a retrospectively-gated breath-hold spiral phase velocity mapping sequence with high temporal resolution (19 ms). A breath-hold segmented gradient echo sequence was used to acquire through-plane cross sectional area changes in the proximal ascending aorta which were used as a surrogate of an aortic pressure waveform after calibration with brachial blood pressure measured with a sphygmomanometer. CMR-derived aortic pressures and CMR-measured velocities were used to derive wave intensity. The CMR-derived wave intensities were compared to invasive data in 12 coronary arteries (8 left, 4 right). Waves were presented as absolute values and as a % of total wave intensity. Intra-study reproducibility of invasive and non-invasive WIA was assessed using Bland-Altman analysis and the intraclass correlation coefficient (ICC). RESULTS: The combination of the CMR-derived pressure and velocity data produced the expected pattern of forward and backward compression and expansion waves. The intra-study reproducibility of the CMR derived wave intensities as a % of the total wave intensity (mean ± standard deviation of differences) was 0.0 ± 6.8%, ICC = 0.91. Intra-study reproducibility for the corresponding invasive data was 0.0 ± 4.4%, ICC = 0.96. The invasive and CMR studies showed reasonable correlation (r = 0.73) with a mean difference of 0.0 ± 11.5%. CONCLUSION: This proof of concept study demonstrated that CMR may be used to perform coronary WIA non-invasively with reasonable reproducibility compared to invasive WIA. The technique potentially allows WIA to be performed in a wider range of patients and pathologies than those who can be studied invasively.

Mechanisms of Myocardial Ischemia in Hypertrophic Cardiomyopathy: Insights From Wave Intensity Analysis and Magnetic Resonance.

BACKGROUND: Angina is common in hypertrophic cardiomyopathy (HCM) and is associated with abnormal myocardial perfusion. Wave intensity analysis improves the understanding of the mechanics of myocardial ischemia. OBJECTIVES: Wave intensity analysis was used to describe the mechanisms underlying perfusion abnormalities in patients with HCM. METHODS: Simultaneous pressure and flow were measured in the proximal left anterior descending artery in 33 patients with HCM and 20 control patients at rest and during hyperemia, allowing calculation of wave intensity. Patients also underwent quantitative first-pass perfusion cardiac magnetic resonance to measure myocardial perfusion reserve. RESULTS: Patients with HCM had a lower coronary flow reserve than control subjects (1.9 ± 0.8 vs. 2.7 ± 0.9; p = 0.01). Coronary hemodynamics in HCM were characterized by a very large backward compression wave during systole (38 ± 11% vs. 21 ± 6%; p < 0.001) and a proportionately smaller backward expansion wave (27% ± 8% vs. 33 ± 6%; p = 0.006) compared with control subjects. Patients with severe left ventricular outflow tract obstruction had a bisferiens pressure waveform resulting in an additional proximally originating deceleration wave during systole. The proportion of waves acting to accelerate coronary flow increased with hyperemia, and the magnitude of change was proportional to the myocardial perfusion reserve (rho = 0.53; p < 0.01). CONCLUSIONS: Coronary flow in patients with HCM is deranged. Distally, compressive deformation of intramyocardial blood vessels during systole results in an abnormally large backward compression wave, whereas proximally, severe left ventricular outflow tract obstruction is associated with an additional deceleration wave. Perfusion abnormalities in HCM are not simply a consequence of supply/demand mismatch or remodeling of the intramyocardial blood vessels; they represent a dynamic interaction with the mechanics of myocardial ischemia that may be amenable to treatment.

Validation of high temporal resolution spiral phase velocity mapping of temporal patterns of left and right coronary artery blood flow against Doppler guidewire.

BACKGROUND: Temporal patterns of coronary blood flow velocity can provide important information on disease state and are currently assessed invasively using a Doppler guidewire. A non-invasive alternative would be beneficial as it would allow study of a wider patient population and serial scanning. METHODS: A retrospectively-gated breath-hold spiral phase velocity mapping sequence (TR 19 ms) was developed at 3 Tesla. Velocity maps were acquired in 8 proximal right and 15 proximal left coronary arteries of 18 subjects who had previously had a Doppler guidewire study at the time of coronary angiography. Cardiovascular magnetic resonance (CMR) velocity-time curves were processed semi-automatically and compared with corresponding invasive Doppler data. RESULTS: When corrected for differences in heart rate between the two studies, CMR mean velocity through the cardiac cycle, peak systolic velocity (PSV) and peak diastolic velocity (PDV) were approximately 40 % of the peak Doppler values with a moderate - good linear relationship between the two techniques (R(2): 0.57, 0.64 and 0.79 respectively). CMR values of PDV/PSV showed a strong linear relationship with Doppler values with a slope close to unity (0.89 and 0.90 for right and left arteries respectively). In individual vessels, plots of CMR velocities at all cardiac phases against corresponding Doppler velocities showed a consistent linear relationship between the two with high R(2) values (mean +/-SD: 0.79 +/-.13). CONCLUSIONS: High temporal resolution breath-hold spiral phase velocity mapping underestimates absolute values of coronary flow velocity but allows accurate assessment of the temporal patterns of blood flow.

Rates and causes of death from non-ST elevation acute coronary syndromes: ten year follow-up of the PRAIS-UK registry.

BACKGROUND: Long term nationally representative mortality rates following acute coronary syndrome (ACS) admissions are lacking beyond 5 years. We report rates and causes of mortality at approximately 10 years from PRAIS-UK. METHODS: PRAIS-UK was a prospective registry of 1046 non-ST-elevation ACS admissions to 56 UK hospitals between 1998 and 1999. 493 patients surviving to 6 months were consented to long term follow-up. We identified deaths and causes (ICD codes) via the UK central death register and examined the influence of baseline characteristics and early revascularisation procedures. A modified GRACE risk score was constructed to determine the association of baseline score with long term risk of death. RESULTS: The mean age was 66 years and 40% were women. After a median follow-up of 11.6 years (IQR 6.3-11.9), 46% (225) of patients had died with 55% being classified as cardiovascular. In a multivariate analysis, the following variables were associated with higher mortality (hazard ratio [HR] and 95% confidence intervals [CI]): age (10 years increase) 2.14 (1.87 to 2.45), ST depression or bundle branch block (compared to normal ECG) 1.68 (1.06 to 2.67), and history of heart failure (compared to no HF) 1.81 (1.28 to 2.56). The HR for risk of death in patients who received a revascularisation procedure (versus those who did not) in the first 6 months was 0.41 (0.24 to 0.69). The mean adapted GRACE score was 99.3 ± 26.4, associated with approximately 50% mortality at 10 years. CONCLUSIONS: Non-ST elevation ACS is associated with about 50% mortality over 10 years that may be improved by early revascularisation. Well designed long-term registries can provide key data to determine prognosis and burden of disease.

The feasibility of nurse-led assessment in acute chest pain admissions by means of coronary computed tomography.

BACKGROUND: Cardiac computed tomography (CCT) is a non-invasive imaging technique for the diagnosis of coronary artery disease (CAD). The National Institute for Health and Clinical Excellence (NICE) recommend CCT for selected patients in the assessment of chest pain of recent onset. AIMS: To assess the feasibility and utility of CCT in a nurse-led, protocol-based assessment of chest pain. METHODS: Patients admitted over 4 months with suspected angina were assessed for eligibility for CCT by a specialist nurse. Eligibility was defined by: a likelihood of CAD < 90%, no features of acute coronary syndrome, no contra-indications to the scanning process, and the ability to give written consent. An age and sex-matched historical cohort (for whom CCT was unavailable) was compared with the CCT cohort with regard to the diagnosis or exclusion of CAD at 3 months post-discharge from hospital. RESULTS: Of 198 patients admitted, 98 were identified as eligible for CCT. Of these, 37 were recommended for alternative management on cardiologist review, 18 declined consent, 23 were unable to be scanned within 24 h prior to discharge and 14 underwent CCT. CAD was diagnosed or excluded in 14/14 patients undergoing CCT. CAD was diagnosed or excluded in 11/14 patients investigated without CCT, leaving 3/14 patients with no clear diagnosis. CONCLUSION: This study suggests nurses may be trained to assess patients for CCT within agreed protocols. In the UK it is likely these protocols will be based on NICE guidance. Despite potential diagnostic utility, CCT appears likely to form a small percentage of cardiac investigations undertaken.

Variable presentation of ventricular tachycardia-like electrocardiographic artifacts.

Diagnosis of clinically significant ventricular tachycardia (VT) relies on accurate electrocardiogram (ECG) interpretation, in the context of a convincing clinical picture. ECG artifacts resembling VT are common and can be misleading. We present two instances of VT-like ECG artifacts, which demonstrate the variable presentation of such artifacts and highlight ways in which these ECG tracings can be distinguished from true VT.

Portentous pinball.

A 76-year-old woman presented with a six-day history of pleuritic pain, dyspnea and a swollen, tender left calf. She was dyspneic, tachypneic and tachycardic (heart rate 109 beats/min), with decreased oxygen saturation (83%) and a partial pressure of oxygen of 9 kPa. Her blood pressure was 119/79 mmHg, and she had elevated jugular venous pressure (11 mmHg). A computed tomographic pulmonary angiogram revealed extensive bilateral pulmonary artery thrombi and an ultrasound confirmed a lower limb thrombus. Echocardiography demonstrated a dilated right ventricle with pulmonary artery hypertension (75 mmHg) and a free-floating thrombus of 1.5 cm x 4 cm, which ricocheted across the right ventricular outflow tract from the tricuspid to the pulmonary valve. The left ventricle was underfilled and hyperdynamic. Following thrombolysis, the patient's clinical status improved. Echocardiography revealed improved biventricular function, no residual right ventricular thrombus, and pulmonary artery pressure normalization. The present case demonstrates the usefulness of echocardiography in submassive pulmonary embolus risk stratification and management.

Generalizing results of randomized trials to clinical practice: reliability and cautions.

BACKGROUND: Well designed randomized controlled trials provide reliable evidence of treatment effects, but there is no consensus on how best to apply these results to clinical practice. The main concerns are that populations enrolled in trials are more selected than those treated in a clinical setting, and whether the treatment effects observed in trials will also be observed in clinical practice. METHODS: An informal literature review was undertaken to find studies analysing the issue of generalizing trial results (external validity) to clinical practice. RESULTS: Most of the studies focused on differences in patients characteristics (age, gender, severity of disease, concomitant treatments and so on) between the clinical trial population and a 'real world' clinical population. None provided good evidence of a reduction in the treatment effect in the trial compared to what might happen in clinical practice for simple pharmacological treatments. However complex treatments like surgery or percutaneous interventional procedures, had a greater potential for variation. Extrapolating treatments to different health care settings from the trial can result in important variations in treatment effects. CONCLUSIONS: Complex therapies need careful consideration before they can be applied routinely from trials into practice, and applying results from one health care environment to a different one should be carried out with caution. Generalizing results from well conducted trials to clinical practice can mostly be carried out with confidence, especially for simple therapies with good evidence of benefit.

Successful crossing of a severe spasm of the brachial artery using a telescopic approach.

We describe a case of severe brachial artery spasm resistant to vasodilator treatment. A multi-purpose 110 cm diagnostic catheter was used as an inner dilator. This allowed easy negotiation of a guiding catheter through the tortuous segment and successful completion of the angioplasty procedure.

The management and investigation of elderly patients with acute coronary syndromes without ST elevation: an evidence-based approach? Results of the Prospective Registry of Acute Ischaemic Syndromes in the United Kingdom (PRAIS-UK).

BACKGROUND: In the elderly, acute coronary syndromes (ACS) without ST elevation are a frequent and important cause of admission. In the UK, practice patterns and outcomes in these patients need to be assessed. METHODS: We enrolled 1,046 patients admitted with ACS without ST elevation to 56 UK centres (20 consecutive patients per centre) and followed them for 6 months. We compared baseline characteristics, outcomes and treatments in those aged 80 and over (n = 119, 11%), from 70 to 79 (n = 301, 29%), from 60 to 69 (n = 283, 27%) with those below 60 (n = 343, 33%). RESULTS: The proportions of males were 40, 52, 67 and 70%, respectively (P < 0.001). There were no differences in the proportion of patients with diabetes (17% overall), treated hypertension (38%) or prior myocardial infarction (MI) (48%). The proportions with ST depression or bundle branch block on admission ECG were 40, 39%, and 28, 18% (P < 0.001), respectively. The rates of the composite endpoint of death or new MI at 6 months were 20, 18, 12 and 6% (P < 0.001), respectively. Heparin, beta blockers and statins were used in significantly higher proportions in younger patients compared with older patients. Similarly, older patients had significantly lower rates of angiography and revascularisation compared with younger patients. CONCLUSION: In this large population-based registry of UK patients admitted to hospital with ACS without ST elevation, those aged over 70 are at substantially higher risk of adverse events than younger patients. However, they are less likely to receive treatments of proven benefit or to be investigated with a view to revascularisation. A more aggressive approach to these patients may be more appropriate and is likely to result in substantial benefits.

Influence of valve prosthesis type on the recovery of ventricular dysfunction and subendocardial ischaemia following valve replacement for aortic stenosis.

BACKGROUND: Long-standing aortic stenosis (AS) causes significant progressive left ventricular (LV) dysfunction and may result in subendocardial ischaemia. Following aortic valve surgery, LV function may improve and this may be accompanied by reversal of ischaemia. There is debate about the differential effects of valve substitutes. METHODS: We studied 33 patients with significant AS and impaired LV systolic function. Patients underwent trans-thoracic Doppler echocardiography and 12-lead electrocardiography pre-operatively, prior to discharge from hospital and at 2.5 (range 1.5-3) years follow-up. RESULTS: Twenty patients received a stentless valve and 13 a stented valve. No patient had significant aortic regurgitation, other valvular disease or coronary artery disease. LV fractional shortening (FS) increased from 19+/-6% to 26+/-7% post-operatively and to 33+/-12% at follow-up in the stentless group (p<0.001). In the stented group, no significant change was seen in the post-operative FS, although it improved at follow-up and at this point did not differ from the stentless group. LV mass fell from 338+/-72 to 265+/-64 g post-operatively and to 170+/-77 g at follow-up (p<0.001) in the stentless group, whereas in the stented group a significant fall was seen only at follow-up (329+/-51 g pre-operatively, 304+/-68 g post-operatively, 166+/-28 g at follow-up, p=0.01). LV free wall excursion increased from 0.8+/-0.3 to 1.1+/-0.4 cm (p=0.05) and to 1.4+/-0.3 cm (p=0.02 compared with pre-operative values) in the stentless group. In the stented group, values were 1.0+/-0.4, 1.0+/-0.3 and 1.3+/-0.2 cm (p=0.05 compared with pre-operative) at the three time points, respectively. QRS duration fell from 113+/-36 ms pre-operatively to 99+/-12 ms at follow-up in the stentless group and from 117+/-28 to 99+/-19 ms in the stented group, p=0.01 for both comparisons. QT interval fell from 385+/-54 ms pre-operatively to 366+/-39 ms at follow-up (p=0.04) in the stentless group with no significant change in the stented group (387+/-52 and 375+/-33 ms, p=0.24). There was reversal of LV strain pattern in 11 (55%) of the stentless group and 6 (46%) of the stented group and normalisation of the inverted U wave in two thirds of patients. CONCLUSION: In patients with AS and severe LV dysfunction, there is a more rapid improvement in LV function following aortic valve replacement with a stentless prosthesis. Improvements in those receiving stented valves appear delayed, although there were no differences between the groups in LV function or mass at follow-up. Normalisation of LV free wall systolic behaviour, narrowing of the QRS complex and a reduction in the QT interval suggest that AS is associated with subendocardial ischaemia that reverses following valve replacement.

Mortality following non-ST elevation acute coronary syndrome: 4 years follow-up of the PRAIS UK Registry (Prospective Registry of Acute Ischaemic Syndromes in the UK).

AIM: To present information on long-term prognosis and risk factors following an admission with non-ST elevation acute coronary syndrome. METHODS: A cohort of 653 patients was followed for mortality and causes of death using data from the UK Office of National Statistics (ONS). Cox proportional hazards model was used to identify the prognostic factors. RESULTS: Overall survival at a maximum follow-up of 45 months was 77.8% (95% CI 74.1-81.1%). Seventy-three per cent of the deaths were clearly due to a cardiovascular cause. Age, male gender, heart failure, ST depression or bundle branch block were all associated with higher short- and long-term risk. Taking aspirin or having a revascularization procedure, over the period of six months following initial hospitalisation were both associated with a lower long-term risk. CONCLUSION: Non-ST elevation acute coronary syndromes carry a high risk of death over a 4-year period. Conventional risk factors can predict both short- and long-term risk. More invasive management and the use of evidence-based therapies appear to be associated with a lower risk.

Effects of valve replacement on left ventricular function in patients with aortic regurgitation and severe ventricular disease.

BACKGROUND AND AIM OF THE STUDY: Longstanding aortic regurgitation (AR) can result in left ventricular (LV) dysfunction that may reverse after aortic valve replacement (AVR). Stentless valves may result in a more rapid recovery in function due to a more physiological flow and lower outflow resistance. METHODS: The effect of AVR on LV function was studied in 47 patients who received either a stentless (n = 33) or stented (n = 14) valve for isolated AR. All patients had evidence of pre-existing LV dysfunction (end-systolic dimension (ESD) >50 mm). Patients were studied using transthoracic echocardiography at baseline, postoperatively, and at 2.5-year follow up. RESULTS: Preoperatively, there were no differences in LV dimensions. The end-diastolic dimension fell from 75 +/- 10 mm to 61 +/- 10 mm postoperatively and to 52 +/- 10 mm at follow up in the stentless group (p <0.001), and ESD fell from 54 +/- 10 mm to 36 +/- 8 mm at follow up (p <0.001). There were no significant early changes in patients who received stented valves, though LV dimensions fell at follow up. Fractional shortening (FS) increased from 25 +/- 8% in the postoperative period to 31 +/- 7% in the stentless group (p <0.001), but there was no change in the stented group (20 +/- 7% versus 23 +/- 8%). In the stentless group, LV mass fell from 366 +/- 104 g to 276 +/- 68 g postoperatively and to 219 +/- 79 g at follow up (p <0.001); there was no postoperative change in the stented group, though a late reduction occurred, from 349 +/- 51 g preoperatively to 265 +/- 61 g at follow up (p = 0.06). CONCLUSION: For patients with AR and LV dysfunction, AVR with a stentless prosthesis offers early reductions in LV dimensions, improved LV function, and regression of LV mass. In patients who received a stented valve, these improvements were delayed and less complete. Hence, for some patients with AR and LV dysfunction, a stentless prosthesis may be preferable.

National economic impact of tirofiban for unstable angina and myocardial infarction without ST elevation; example from the United Kingdom.

BACKGROUND: Acute coronary syndromes without ST elevation are a major health and economic burden. Treatments such as glycoprotein IIb/IIIa antagonists like tirofiban reduce the risk of complications but the cost impact of these agents including cost offsets of avoiding complications are needed particularly in Europe. METHODS: We used treatment patterns from the Prospective Registry of Acute Ischemic Syndromes in the UK, risk reductions derived from the PRISM-PLUS trial and cost estimates from the CHKS database to estimate the impact of tirofiban on PRAIS-UK patients with and without complications and subgroups at higher risk of complications. These subgroups (and proportions) were patients: (1) aged 60 or over with abnormal electrocardiograms (58%), (2) with ST depression or bundle branch block on admission (30%) and (3) with ST depression, bundle branch block or MI on admission (37%). RESULTS: Total cost of care in the UK at 6 months for the estimated 87339 acute coronary syndromes admissions annually was pound 213 million, which would increase by pound 33 million (15.7%) if tirofiban were given to all patients, avoiding 2422 complications at a mean cost per event avoided of pound 13388. Among the subgroups, the mean cost per event avoided ranges from pound 10856 for subgroup 1 to pound 5953 for subgroup 3. Treating the latter subgroup, would avoid 1977 events at a cost of pound 12 million (5.5%). CONCLUSION: The use of tirofiban in the UK to treat acute coronary syndromes patients without ST elevation provides an important therapeutic advantage at modest proportional increase in cost, particularly if targeted to higher risk subgroups as recommended in the European guidelines.