P D Lambiase

Systemic inflammation in unstable angina is the result of myocardial necrosis

OBJECTIVESnWe investigated whether the source of the acute phase response in unstable angina (UA) lay within the culprit coronary plaque or distal myocardium.nnnBACKGROUNDnAn inflammatory response is an important component of the acute coronary syndromes. However, its origin and mechanism remain unclear.nnnMETHODSnIn 94 stable patients undergoing coronary angiography, the relationship between systemic levels of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6) and C-reactive protein (CRP) and extent of atherosclerosis was studied. The temporal relationship between these markers and troponin T (TnT) was determined in 91 patients with UA. Cytokine levels were measured in the aortic root and coronary sinus of 36 unstable patients.nnnRESULTSnThere was no relationship found between stable coronary atherosclerosis and inflammatory marker levels. Compared with this group, admission levels of IL-6 (3.6 +/- 0.3 ng/ml vs. 10.7 +/- 1.7 ng/ml, p < 0.05) and CRP (2.3 +/- 0.1 mg/l vs. 4.6 +/- 0.6 mg/l, p < 0.05) were elevated in patients with UA. In this group, IL-6 and CRP remained elevated in those who subsequently experienced major adverse cardiac events. This inflammatory response occurred in parallel to the appearance of TnT. Both TNF-alpha (19.2 +/- 3.4 ng/ml vs. 17.1 +/- 3.3 ng/ml, p < 0.001) and IL-6 (10.3 +/- 1.4 ng/ml vs. 7.7 +/- 1.1 ng/ml, p < 0.01) were elevated in the coronary sinus compared with aortic root in patients with UA. This was principally observed in those who were TnT positive. There was no cytokine gradient across the culprit plaque.nnnCONCLUSIONSnThere is an intracardiac inflammatory response in UA that appears to be the result of low-grade myocardial necrosis. The ruptured plaque does not appear to contribute to the acute phase response.

Simulation of cardiac pathologies using an electromechanical biventricular model and XMR interventional imaging

Simulating cardiac electromechanical activity is of great interest for a better understanding of pathologies and for therapy planning. Design and validation of such models is difficult due to the lack of clinical data. XMR systems are a new type of interventional facility in which patients can be rapidly transferred between X-ray and MR systems. Our goal is to design and validate an electromechanical model of the myocardium using XMR imaging. The proposed model is computationally fast and uses clinically observable parameters. We present the integration of anatomy, electrophysiology, and motion from patient data. Pathologies are introduced in the model and simulations are compared to measured data. Initial qualitative comparison on the two clinical cases presented is encouraging. Once fully validated, these models will make it possible to simulate different interventional strategies.

Exercise-induced ischemia initiates the second window of protection in humans independent of collateral recruitment

OBJECTIVESnThis study was designed to examine if exercise-induced ischemia initiated late preconditioning in humans that becomes manifest during subsequent exercise and serial balloon occlusion of the left anterior descending coronary artery (LAD).nnnBACKGROUNDnThe existence of late preconditioning in humans is controversial. We therefore compared myocardial responses to exercise-induced and intracoronary balloon inflation-induced ischemia in two groups of patients subjected to different temporal patterns of ischemia.nnnMETHODSnThirty patients with stable angina secondary to single-vessel LAD disease underwent percutaneous coronary intervention (PCI) after two separate exercise tolerance test (ETT) protocols designed to investigate isolated early preconditioning (IEP) alone or the second window of protection (SWOP). The IEP subjects underwent three sequential ETTs at least two weeks before PCI. The SWOP subjects underwent five sequential ETTs commencing 24 h before PCI.nnnRESULTSnDuring PCI there was no significant difference in intracoronary pressure-derived collateral flow index (CFI) between groups (IEP = 0.15 +/- 0.13, SWOP = 0.19 +/- 0.15). In SWOP patients, compared with the initial ETT, the ETT performed 24 h later had a 40% (p < 0.001) increase in time to 0.1-mV ST depression and a 60% (p < 0.05) decrease in ventricular ectopic frequency. During the first balloon inflation, peak ST elevation was reduced by 49% (p < 0.05) in the SWOP versus the IEP group, and the dependence on CFI observed in the IEP group was abolished (analysis of covariance, p < 0.05). The significant attenuation of ST elevation (47%, p < 0.005) seen at the time of the second inflation in the IEP patients was not seen in the SWOP patients.nnnCONCLUSIONSnExercise-induced ischemia triggers late preconditioning in humans, which becomes manifest during exercise and PCI. This is the first evidence that ischemia induced by coronary occlusion is attenuated in humans by a late preconditioning effect induced by exercise.

Relationship between endocardial activation sequences defined by high-density mapping to early septal contraction (septal flash) in patients with left bundle branch block undergoing cardiac resynchronization therapy

AIMSnEarly inward motion and thickening/thinning of the ventricular septum associated with left bundle branch block is known as the septal flash (SF). Correction of SF corresponds to response to cardiac resynchronization therapy (CRT). We hypothesized that SF was associated with a specific left ventricular (LV) activation pattern predicting a favourable response to CRT. We sought to characterize the spatio-temporal relationship between electrical and mechanical events by directly comparing non-contact mapping (NCM), acute haemodynamics, and echocardiography.nnnMETHODS AND RESULTSnThirteen patients (63 ± 10 years, 10 men) with severe heart failure (ejection fraction 22.8 ± 5.8%) awaiting CRT underwent echocardiography and NCM pre-implant. Presence and extent of SF defined visually and with M-mode was fused with NCM bulls eye plots of endocardial activation patterns. LV-dP/dt(max) was measured during different pacing modes. Five patients had a large SF, four small SF, and four no SF. Large SF patients had areas of conduction block in non-infarcted regions, whereas those with small or no SF did not. Patients with large SF had greater acute response to LV and biventricular (BIV) pacing vs. those with small/no SF (% increase dP/dt 28 ± 14 vs. 11 ± 19% for LV pacing and 42 ± 28 vs. 22 ± 21% for BIV pacing) (P < 0.05). This translated into a more favourable chronic response to CRT. The lines of conduction block disappeared with LV/BIV pacing while remaining with right ventricle pacing.nnnCONCLUSIONnA strong association exists between electrical activation and mechanical deformation of the septum. Correction of both mechanical synchrony and the functional conduction block by CRT may explain the favourable response in patients with SF.

The relationship of systemic right ventricular function to ECG parameters and NT-proBNP levels in adults with transposition of the great arteries late after Senning or Mustard surgery

Aims Heart failure is common late after Senning or Mustard palliation of transposition of the great arteries (TGA). Although cardiac magnetic resonance (CMR) is the gold standard for evaluating systemic right ventricular performance, additional information regarding heart failure status might be gleaned from the surface ECG and circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. The interrelationships between these heart failure markers were examined in adults late after Mustard and Senning surgery. Methods Thirty-five consecutive adults with Senning or Mustard repair of TGA attending a dedicated congenital heart failure clinic were studied. Assessment included symptom assessment, venous blood sampling for measurement of circulating NT-proBNP levels, surface 12-lead ECG and CMR for the assessment of right ventricular systolic function and determination of indexed right ventricular volumes. Results Mean age was 29±6.5u2005years, 54% had undergone Mustard surgery. Compared with those with uncomplicated surgery, patients with complex surgical history had higher NT-proBNP levels (55±26 vs 20±35u2005pmol/l; p=0.002) and longer QRS duration (116±28u2005ms vs 89±11u2005ms; p=0.0004) while showing no difference in New York Heart Association class and right ventricular function. There was a significant relationship between diastolic and systolic right ventricular volumes and both NT-proBNP levels (r=0.43, p=0.01; r=0.53, p=0.001, respectively) and QRS duration (r=0.47, p=0.004; r=0.53, p=0.001, respectively). Conclusions Circulating NT-proBNP levels and several surface ECG parameters constitute safe, cost-effective and widely available surrogate markers of systemic right ventricular function and provide additional information on heart failure status. Both measures hold promise as prognostic markers and their association with long-term outcome should be determined.

Electrical remodeling following percutaneous pulmonary valve implantation.

Sudden cardiac death in congenital heart disease is related to increased right ventricular end-diastolic volume (RVEDV), abnormalities of QRS duration, and QRS, JT, and QT dispersions. Surgical pulmonary valve replacement and percutaneous pulmonary valve implantation (PPVI) decrease RVEDV, but the effects of PPVI on surface electrocardiographic parameters are unknown. PPVI represents a pure model of RV mechanical and electrophysiologic changes after replacement. This prospective study sought to determine the effects of PPVI on surface electrocardiographic parameters: Ninety-nine PPVI procedures in patients with congenital heart disease (23.1 ± 10 years of age) were studied before, after, and 1 year after PPVI with serial electrocardiograms and echocardiogram/magnetic resonance images. Forty-three percent had pulmonary stenosis, 27% pulmonary regurgitation (PR), and 29% mixed lesions. In those with predominantly PR (n = 26), QRS duration decreased significantly (135 ± 27 to 128 ± 29 ms, p = 0.007). However, in the total cohort no significant change in QRS duration at 1 year was observed (137 ± 29 to 134 ± 29 ms). Corrected QT interval and QRS, QT, and JT dispersions significantly decreased at 1 year (p ≤0.001). RVEDV correlated with preprocedure QRS duration (r = 0.34, p <0.002) but there was no correlation after PPVI. In conclusion, this is the first study reporting electrical remodeling after isolated PPVI and it confirms that decreases in QRS duration occur after PPVI in PR, as reported for equivalent surgical cohorts. Further, increased homogeneity of repolarization in combination with improved conduction may decrease arrhythmic events in congenital cardiac patients with pulmonary valvular disease.

Antiarrhythmic and anti-ischaemic effects of angina in patients with and without coronary collaterals

Objective: To determine whether the changes in the manifestations of myocardial ischaemia during sequential angina episodes caused by exercise or coronary artery occlusion are collateral dependent. Methods: 40 patients awaiting percutaneous transluminal coronary angioplasty for an isolated left anterior descending artery stenosis underwent three sequential treadmill exercise tests, with the second exertion separated from the first by 15 minutes, and from the third by 90 minutes; 28 patients subsequently completed two (> 180 s) sequential intracoronary balloon inflations with measurement of collateral flow index from mean coronary artery wedge, aortic, and coronary sinus pressures. Results: On second compared with first exercise, time to 0.1 mV ST depression (mean (SD): 340 (27) v 266 (25) s) and rate–pressure product at 0.1 mV ST depression (22 068 (725) v 19 586 (584) beats/min/mm Hg) were increased (all p < 0.005), while angina and ventricular ectopic beat frequency were diminished (p < 0.05). This advantage, which had waned by the third effort, was independent of collateral flow index. Similarly, at the end of the second compared with the first coronary occlusion, ventricular tachycardia (21% v 0%, p < 0.05), ST elevation (0.47 (0.07) v 0.33 (0.05) mV, p < 0.005), and angina severity (6.1 (0.7) v 4.6 (0.7) units, p < 0.005) were reduced despite similar collateral flow indices. Conclusions: In patients with coronary artery disease, ventricular arrhythmias, ST deviation, and angina are reduced during a second exertion or during a second coronary occlusion. This protective effect can occur independently of collateral recruitment. These characteristics, together with the breadth and temporal pattern of protection, are consistent with ischaemic preconditioning.

Myocardial gene and cell delivery

Although we now have the tools to introduce vectors and stem cells into specific myocardial locations, these devices are yet to be matched by comparable advances in molecular virology, cell biology, and our understanding of the pathophysiology of ischaemic heart disease

A multi-purpose spiral high-density mapping catheter: initial clinical experience in complex atrial arrhythmias

PurposeThere is an increasing need for catheter ablation procedures to treat complex atrial tachycardias (AT) and atrial fibrillation (AF), often requiring detailed endocardial mapping. The sequential point-to-point contact mapping of complex arrhythmias is time-consuming and may not always be feasible. We assessed the utility of a novel spiral duo-decapolar high-density (HD) mapping catheter to delineate complex arrhythmia substrates for ablation.MethodsThe patients underwent HD mapping using a spiral catheter (AFocusII) and the EnSite NavX system, during catheter ablation procedures, to treat atrial arrhythmias.ResultsIn 26 patients, a total of 32 atrial arrhythmias were mapped and ablated, comprising of five focal AT, eight macroreentrant AT, 11 persistent AF and eight paroxysmal AF. The HD catheter was used to acquire endocardial surface geometries in all cases and to map the pulmonary veins in patients undergoing AF ablation. In persistent AF, HD catheter mapping permitted the creation of highly detailed complex fractionated electrogram maps (left atrium 449u2009±u2009128 points in 7.2u2009±u20092.6xa0min; right atrium 411u2009±u2009113 points in 6.7u2009±u20091.6xa0min). In AT, activation mapping was performed with the acquisition of 305u2009±u2009158 timing points in 7.3u2009±u20092.6xa0min, guiding successful ablation in all cases. During the follow-up of 7.0u2009±u20092.6xa0months, all AT patients remained free of significant arrhythmia.ConclusionsHigh-density contact mapping with a novel spiral multipolar catheter allows rapid assessment of focal and macroreentrant AT, and complex fractionated electrical activity in the atria. It has further multi-functional capabilities as a pulmonary vein mapping catheter and for accurate geometry creation when used with a 3D mapping system.

The use of a novel nitinol guidewire to facilitate transseptal puncture and left atrial catheterization for catheter ablation procedures

AIMSnAn increasing number of transseptal punctures (TSPs) are performed worldwide for atrial ablations. Transseptal punctures can be complex and can be associated with potentially life threatening complications. The purpose of the study was to evaluate the safety and efficacy of a novel transseptal guidewire (TSGW) designed to facilitate TSPs.nnnMETHODS AND RESULTSnTransseptal punctures were performed using a SafeSept TSGW passed through a standard TSP apparatus. Transseptal punctures were performed by standard technique with additional use of a TSGW allowing probing of the interatrial septum without needle exposure and penetration of the fossa into the left atrium (LA). Transseptal puncture using the TSGW was performed in 210 patients. Left atrial access was achieved successfully in 205 of 210 patients (97.6%) and in 96.3% of patients undergoing repeat TSP. Left atrial access was achieved with the first pass in 81.2% (mean 1.4 ± 0.9 passes, range 1-6) using the TSGW. No serious complications were attributable to the use of the TSGW, even in cases of failed TSP.nnnCONCLUSIONSnThe TSGW is associated with a high success rate for TSP and may be a useful alternative to transoesophageal or intracardiac echocardiogram-guided TSP.