Colin Forfar

Dynamic Changes of Edema and Late Gadolinium Enhancement after Acute Myocardial Infarction and Their Relationship to Functional Recovery and Salvage Index

Background— Changes in the myocardium in acute ischemia are dynamic and complex, and the characteristics of myocardial tissue on cardiovascular magnetic resonance in the acute setting are not fully defined. We investigated changes in edema and late gadolinium enhancement (LGE) with serial imaging early after acute myocardial infarction, relating these to global and segmental myocardial function at 6 months. Methods and Results— Cardiovascular magnetic resonance scans were performed on 30 patients with ST-elevation–myocardial infarction treated by primary percutaneous coronary intervention at each of 4 time points: 12 to 48 hours; 5 to 7 days; 14 to 17 days; and 6 months. All patients showed edema at 24 hours. The mean volume of edema (% left ventricle) was 37±16 at 24 hours and 39±17 at 1 week, with a reduction to 24±13 (P<0.01) by 2 weeks. Myocardial segments with edema also had increased signal on LGE at 24 hours (&kgr;=0.77; P<0.001). The volume of LGE decreased significantly between 24 hours and 6 months (27±15% versus 22±12%; P=0.002). Of segments showing LGE at 24 hours, 50% showed resolution by 6 months. In segments with such a reduction in LGE, 65% also showed improved wall motion (P<0.0001). The area of LGE measured at 6 months correlated more strongly with troponin at 48 hours (r=0.9; P<0.01) than LGE at 24 hours (r=0.7). The difference in LGE between 24 hours and 6 months had profound effects on the calculation of salvage index (26±21% at 24 hours versus 42±23% at 6 months; P=0.02). Conclusions— Myocardial edema is maximal and constant over the first week after myocardial infarction, providing a stable window for the retrospective evaluation of area at risk. By contrast, myocardial areas with high signal intensity in LGE images recede over time with corresponding recovery of function, indicating that acutely detected LGE does not necessarily equate with irreversible injury and may severely underestimate salvaged myocardium.

Comparison of different methods for assessing sympathovagal balance in chronic congestive heart failure secondary to coronary artery disease

Twenty-five patients (aged 62 +/- 2 years) with stable, moderate to severe ischemic congestive heart failure (CHF) (New York Heart Association class II/III: 15/10; ejection fraction 21.6 +/- 2%; and peak oxygen uptake 13.6 +/- 0.7 ml/kg/min) were studied to evaluate the ability of different methods to characterize autonomic tone in chronic CHF. Sympathovagal balance was assessed by: (1) heart rate variability in the time domain, assessed by the SD of RR intervals; (2) heart rate variability in the frequency domain, assessed by low- (0.03 to 0.14 Hz) and high- (0.18 to 0.40 Hz) frequency components of heart rate variability by autoregressive power spectral analysis; (3) 24-hour, daytime and nighttime heart rate; (4) submaximal heart rate during upright bicycle exercise, with respiratory gas analysis to obtain peak oxygen uptake; and (5) radiolabeled norepinephrine spillover. These methods did not correlate, with the exception of day and nighttime heart rate (r = 0.74; p < 0.001) and the expected inverse correlation between low and high frequency (r = -0.92; p < 0.001). No method correlated significantly with peak oxygen uptake, exercise tolerance or ejection fraction. After 8 weeks of physical training at home, all methods showed improvement in autonomic balance: increases in SD of RR intervals (+21%; p < 0.02) and high frequency (+41%; p < 0.007), and decreases in low frequency (-19%; p < 0.002), low-/high-frequency ratio (-48%; p < 0.03), norepinephrine spillover (-28.9%; p < 0.03), 24-hour heart rate (-2.7%; p < 0.005) and submaximal heart rate (-10.8%; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of pulsed β-stimulant therapy on β-adrenoceptors and chronotropic responsiveness in chronic heart failure

Abstract In animals, intermittent sympathomimetic stimulation with dobutamine produces benefits analogous to those of physical conditioning. Longer intermittent or continuous β-stimulant therapies have not, however, been successful in managing patients with chronic heart failure. We have investigated the role of β-receptor stimulants in patients with severe chronic heart failure by changing the method of administration to intermittent, very short-duration pulsed intrope therapy (PIT). We studied 10 patients (mean age 64 [SE 2] years) with stable moderate to severe chronic heart failure (ejection fraction 23 [3]%) who received PIT, and 10 control patients matched for age and severity. We infused sufficient dobutamine to raise heart rate to 70-80% maximum for 30 min per day, 4 days per week for 3 weeks. PIT increased exercise tolerance (from 10·4 [1·2] min at baseline to 13·0 [1·5] min at 3 weeks; p -1 ; p

The prevalence of obstructive sleep apnoea and its association with aortic dilatation in Marfan’s syndrome

Background: Craniofacial abnormalities and increased pharyngeal collapsibility due to abnormal connective tissue suggest the possibility of an increased prevalence of obstructive sleep apnoea (OSA) in patients with Marfan’s syndrome but the actual prevalence is uncertain. Aortic dilatation and dissection are life threatening manifestations of Marfan’s syndrome and case reports have suggested a possible association with OSA but data from cohort studies are not available. Methods: A sleep study was performed in 61 patients with Ghent criteria positive Marfan’s syndrome (mean age 38.3 (SD 12.9) years; 37 females) and in 26 control subjects matched for age, gender, height and weight. OSA was defined using two conventional levels of apnoea–hypopnoea index (AHI), >5 and >15/h. In patients with Marfan’s syndrome, aortic root diameter was measured by echocardiography. Results: More patients with Marfan’s syndrome than controls had OSA (AHI >5, 32.8% compared with 11.5%, mean difference +21.3%, 95% CI 4.2% to 38.3%, p = 0.04; AHI >15, 18.0% compared with 0%, mean difference +18.0%, 95% CI 8.4% to 27.7%, p = 0.02). AHI was correlated with aortic root diameter (r = 0.50, 95% CI 0.26 to 0.69, p = 0.0003), and mean aortic root diameter was significantly greater in patients with OSA (4.5 (SD 0.6) cm) compared with those without OSA (3.7 (0.6) cm) (mean difference 0.8 cm, 95% CI 0.4 to 1.2 cm, p<0.0001). Conclusions: In patients with Marfan’s syndrome, the prevalence of OSA is considerably higher than in matched control subjects. OSA may be a risk factor for aortic root dilatation in Marfan’s syndrome.

An open study to assess the safety, tolerance and pharmacokinetics of an intravenous infusion of granisetron given at 3 mg over 30 s in patients receiving chemotherapy for malignant disease

Granisetron is a highly potent and selective 5-hydroxytryptamine3 (5-HT3) receptor antagonist indicated for the prevention of cytotoxic-induced nausea and vomiting. Clinical trials have demonstrated granisetron to be effective and well tolerated at a standard dose of 40 μg/kg or 3 mg given i.v. as a 5-min infusion. In this study, the efficacy and safety of granisetron given as a 30-s infusion was assessed. A total of 21 patients, scheduled to undergo chemotherapy, received a single 3-mg i.v. dose of granisetron over 30 s, completed at 1 h before chemotherapy administration. Patients were allowed two further i.v. doses of granisetron at 3 mg within the 24-h assessment period. Changes from baseline values in vital signs were analysed prior to granisetron administration and at 30 s as well as 1, 10, 15, 30 and 60 min after granisetron administration. Holter ECG recordings were taken for 6 h prior to and 1 h after administration. No significant change was found in vital signs at 30 s or 1 min after granisetron infusion. There was a small but statistically significant fall in diastolic blood pressure as compared with baseline and a non-significant trend in favour of a reduction in heart rate at 10 and 15 min. No ECG abnormality was recorded post-infusion that had not been present pre-infusion. None of these changes was considered to be clinically relevant. The treatment was well tolerated. The most frequenctly reported adverse events were constipation (n=6) and headache (n=5). Maximal plasma levels of granisetron were within the range of 44.57–410 ng/ml except in one patient. The median values recorded for peak concentration (Cmax) and area under the curve (AUC) were 195 ng/ml and 71.2 ng h ml−1, respectively. In conclusion, granisetron at 3 mg was shown to be safe and well tolerated when given as a 30-s i.v. infusion to patients receiving chemotherapy for malignant disease.

Contained Left Ventricular Rupture After Acute Myocardial Infarction Revealed by Cardiovascular Magnetic Resonance Imaging

A 69-year-old man with a 2-day history of chest pain was admitted to our hospital. His ECG was consistent with acute coronary syndrome (Figure 1A) and troponin I was elevated (>50 ng/mL). Coronary angiography showed a totally occluded circumflex with extensive intraluminal thrombus but no other obstructive disease (Figure 1B). Because the chest pain had completely resolved and this was a late-presentation myocardial infarction, management was medical. Echocardiography on day 6 showed inferolateral wall akinesis (Figure 1C and 1D) but preserved overall left ventricular (LV) function. Cardiovascular magnetic resonance (CMR) imaging 24 hours later to assess for viability showed an area of extreme thinning in the inferolateral wall due to myocardial rupture contained by overlying pericardium (Figure 1E and 1F, arrow, and online-only Data Supplement Movie I). Images acquired early after gadolinium contrast showed a layer of thrombus overlying the area of rupture (Figure 1G, arrow) and extensive no-reflow within the inferolateral wall (Figure 1G, arrowheads). Review of the echo images revealed an area in the inferolateral wall that could be …

Heart Within a Heart Contrast 3-Dimensional Echocardiography Imaging of a Tricuspid Valve Blood Cyst

An 80-year-old woman was referred with non-sustained palpitations, intermittent presyncope, and atypical chest pain. Examination revealed a loud “plopping” first heart sound and presystolic thrill at the lower left sternal edge. Echocardiography showed a large cystic lesion attached to the septal leaflet of the tricuspid valve, dilatation of the right heart chambers, and moderate tricuspid regurgitation (Figure 1). Three-dimensional contrast echocardiography confirmed the mobile cyst and revealed small lesions within it (Figure 2a); during systole, the cyst became deformable within the ventricle, resulting in a “heart” shape (Figure 2b). The following day, her clinical findings had changed, with loss of the “plopping” first heart sound, a new systolic murmur at the left sternal edge, and loss of the presystolic thrill. Echocardiography confirmed cyst migration into the right ventricular outflow tract with partial obstruction (Figure 3). Emergency resection on cardiopulmonary bypass revealed a blood-filled cyst with small interior cysts that was attached to the tricuspid valve. Histological examination confirmed a simple blood-filled cyst. The patient had an uncomplicated recovery. Blood -filled cysts are typically small and asymptomatic and are most commonly found in infants. In most cases, they regress spontaneously and are rare in adults, but they occasionally obstruct, as in this case.An 80-year-old woman was referred with non-sustained palpitations, intermittent presyncope, and atypical chest pain. Examination revealed a loud “plopping” first heart sound and presystolic thrill at the lower left sternal edge. Echocardiography showed a large cystic lesion attached to the septal leaflet of the tricuspid valve, dilatation of the right heart chambers, and moderate tricuspid regurgitation (Figure 1). Three-dimensional contrast echocardiography confirmed the mobile …

Transventricular Pulmonary Valve Implantation in Corrected Truncus Arteriosus

Conventional surgery for revision of right ventricular outflow tract conduits is complex and demanding. Percutaneous implantation of pulmonary valves may not be feasible in all cases. We describe a safe, alternative hybrid transapical approach from the right ventricle that avoids the extensive dissection and potential complications of revision surgery.

71 Percutaneous Coronary Intervention (PCI) Risk Scores Predicting Inpatient Mortality and Major Adverse Cardiac Events (MACE) are Poorly Concordant in High Risk Patients

Background High-risk percutaneous coronary intervention (PCI) procedures are being performed in greater numbers, in older patients with multiple comorbidities, and increasingly in the setting of acute coronary syndromes. Estimating inpatient PCI mortality and MACE risk (mortality, Q-wave myocardial infarction, urgent coronary artery bypass grafting and stroke) is essential in informing decision-making, consent, and operator and institutional benchmarking. There are a number of currently available risk scores that are often applied interchangeably. We investigated if there was concordance between contemporary risk scoring systems for inpatient mortality and MACE following PCI in patients at low, moderate or high-risk in a ‘real life’ cohort, depending upon method of presentation (elective, urgent, emergency). Methods We retrospectively identified 1,404 consecutive patients treated by PCI within a 6-month period in 2013. The New York risk score (NY) and National Cardiovascular Data Registry score (NCDR) were calculated for each patient to predict inpatient mortality risk and the Northwestern Quality Improvement score (NWQIP) and the Mayo Clinical Risk Score (MCRS) were calculated to predict inpatient MACE risk. Using the NY score as the reference for inpatient mortality and the NWQIP score as the reference for inpatient MACE, patients were divided into three risk groups (low < 1%; moderate 1–5%; high > 5%) and stratified into elective, urgent and emergency clinical presentations. Concordance was estimated using the Intraclass Correlation Coefficient (ICC) calculated with respect to each risk score and stratified by patient group. Results 757 patients were identified as low-risk (461 elective, 280 urgent, 16 emergency), 497 patients as moderate-risk (73 elective, 197 urgent, 227 emergency) and 150 patients as high-risk (4 elective, 43 urgent, 103 emergency) for inpatient mortality. 607 patients were identified as low-risk (382 elective, 225 urgent, 0 emergency), 594 patients as moderate-risk (97 elective, 237 urgent, 260 emergency) and 203 patients as high-risk (14 elective, 66 urgent, 123 emergency) for inpatient MACE events. The ICC indicated that risk scores correlated well for low-risk groups however were poorly concordant for high-risk groups (Table 1) and that this was true regardless of mode of clinical presentation (Table 2). Abstract 71 Table 1 Abstract 71 Table 2 Conclusions Currently available PCI risk scores for both inpatient mortality and MACE are broadly concordant in low risk patient groups. However in patients at higher risk with multiple co-morbid factors, current tools are poorly concordant in predicting mortality and MACE. This has important implications for consent, and benchmark analysis of operator and institutional performance. Better understanding of choice of risk score for use in clinical practice is needed particularly as case mix and complexity evolve.

Improved Coronary Sinus Blood Sampling for Cardiac Research

Background: Coronary sinus (CS) blood sampling is important for measuring metabolites and biomarkers in cardiovascular research, but can be technically challenging. Here we demonstrate the use of the antecubital fossa for CS blood sampling as an alternative to femoral access, and a simple technique of paired venous and CS blood gas analysis for confirmation of valid CS sampling. We also demonstrate improvement in sampling accuracy by using a coronary guide wire to stabilize the sampling catheter in the CS. Methods: Paired blood samples from CS and peripheral vein were collected from patients at the time of primary PCI for acute myocardial infarction. Venous access for CS sampling was via the antecubital vein. Blood gas analysis was used to confirm a true CS sample (pO2[CS]<pO2[v]). CS sampling was carried out with a catheter in the CS (standard technique) or with the addition of a coronary guide wire for stability (modified technique). Results: 108 patients underwent CS and peripheral venous blood sampling. The standard technique for CS sampling was used in 62 patients and the modified technique in 46 patients. Blood gas analysis confirmed a true CS sample in 77% of patients using the standard technique and 100% using the modified technique. Conclusions: CS blood sampling via the antecubital fossa is feasible and safe. Blood gas analysis of paired venous and CS samples can be used to confirm a valid CS sample. A coronary guide wire can be used to stabilise the sampling catheter in the CS, and this increases CS sampling accuracy.