Raymond Tukkie

Lenient versus Strict Rate Control in Patients with Atrial Fibrillation

BACKGROUNDnRate control is often the therapy of choice for atrial fibrillation. Guidelines recommend strict rate control, but this is not based on clinical evidence. We hypothesized that lenient rate control is not inferior to strict rate control for preventing cardiovascular morbidity and mortality in patients with permanent atrial fibrillation.nnnMETHODSnWe randomly assigned 614 patients with permanent atrial fibrillation to undergo a lenient rate-control strategy (resting heart rate <110 beats per minute) or a strict rate-control strategy (resting heart rate <80 beats per minute and heart rate during moderate exercise <110 beats per minute). The primary outcome was a composite of death from cardiovascular causes, hospitalization for heart failure, and stroke, systemic embolism, bleeding, and life-threatening arrhythmic events. The duration of follow-up was at least 2 years, with a maximum of 3 years.nnnRESULTSnThe estimated cumulative incidence of the primary outcome at 3 years was 12.9% in the lenient-control group and 14.9% in the strict-control group, with an absolute difference with respect to the lenient-control group of -2.0 percentage points (90% confidence interval, -7.6 to 3.5; P<0.001 for the prespecified noninferiority margin). The frequencies of the components of the primary outcome were similar in the two groups. More patients in the lenient-control group met the heart-rate target or targets (304 [97.7%], vs. 203 [67.0%] in the strict-control group; P<0.001) with fewer total visits (75 [median, 0], vs. 684 [median, 2]; P<0.001). The frequencies of symptoms and adverse events were similar in the two groups.nnnCONCLUSIONSnIn patients with permanent atrial fibrillation, lenient rate control is as effective as strict rate control and is easier to achieve. (ClinicalTrials.gov number, NCT00392613.)

Routine versus aggressive upstream rhythm control for prevention of early atrial fibrillation in heart failure: background, aims and design of the RACE 3 study.

BackgroundRhythm control for atrial fibrillation (AF) is cumbersome because of its progressive nature caused by structural remodelling. Upstream therapy refers to therapeutic interventions aiming to modify the atrial substrate, leading to prevention of AF.ObjectiveThe Routine versus Aggressive upstream rhythm Control for prevention of Early AF in heart failure (RACE 3) study hypothesises that aggressive upstream rhythm control increases persistence of sinus rhythm compared with conventional rhythm control in patients with early AF and mild-to-moderate early systolic or diastolic heart failure undergoing electrical cardioversion.DesignRACE 3 is a prospective, randomised, open, multinational, multicenter trial. Upstream rhythm control consists of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, mineralocorticoid receptor antagonists, statins, cardiac rehabilitation therapy, and intensive counselling on dietary restrictions, exercise maintenance, and drug adherence. Conventional rhythm control consists of routine rhythm control therapy without cardiac rehabilitation therapy and intensive counselling. In both arms, every effort is made to keep patients in the rhythm control strategy, and ion channel antiarrhythmic drugs or pulmonary vein ablation may be instituted if AF relapses. Total inclusion will be 250 patients. If upstream therapy proves to be effective in improving maintenance of sinus rhythm, it could become a new approach to rhythm control supporting conventional pharmacological and non-pharmacological rhythm control.

Cardiac denervation after clinical transmyocardial laser revascularization: short-term and long-term iodine 123-labeled meta-iodobenzylguanide scintigraphic evidence

OBJECTIVESnThis study was designed to investigate whether transmyocardial laser revascularization induces myocardial denervation and to correlate this with myocardial perfusion and clinical status.nnnMETHODSnTransmyocardial laser revascularization was performed with a Holmium:YAG (n = 3) or xenon chloride excimer laser (n = 5). Preoperative and postoperative iodine 123-labeled meta-iodobenzylguanide SPECT scintigraphy to assess cardiac innervation and perfusion scintigraphy were also performed. Furthermore, New York Heart Association functional angina class and quality of life were assessed.nnnRESULTSnIn all patients postoperative iodine 123-labeled meta-iodobenzylguanide SPECT showed significantly decreased uptake and therefore sympathetic myocardial denervation at up to 16 months follow-up (average preoperative and postoperative summed defect scores of 14.8 +/- 5.3 and 24.5 +/- 4.2, respectively; P =.00005). In 86% of segments, the decreased meta-iodobenzylguanide uptake could be correlated to the treated area. In all patients angina was reduced by 2 or more classes at 12 months follow-up, and quality of life improved significantly.nnnCONCLUSIONSnTransmyocardial laser revascularization-induced improvement of angina and quality of life can be explained by destruction of nociceptors or cardiac neural pathways, changing the perception of anginal pain.

Chest wall reconstruction with degradable processed sheep dermal collagen in dogs

Chest wall defects resulting from oncological operations often require prosthetic repair. The objectives of prosthetic repair are to provide a cosmetically acceptable substitute, prevent paradoxical chest wall movement, and protect vital organs. Of the many materials that have been used in these repairs, none have proved to be ideal. The aim of our study was to investigate the application of a biodegradable material--processed sheep dermal collagen--as a chest wall prosthesis. A full-thickness chest wall defect of 10 x 10 cm was created in 12 dogs; 10 had repair with a processed sheep dermal collagen prosthesis and 2, the controls, with polypropylene mesh. In this study, the biomaterial fulfilled its function as a chest wall prosthesis at 24 weeks follow-up. No respiratory problems were seen, the chest wall remained stable with minimal and decreasing respiratory paradoxical movement, and the processed sheep dermal collagen slowly degraded and was replaced by the host collagen. Processed sheep dermal collagen offers long-term advantages because it is degradable. Late complications from a nonabsorbable prosthesis, ie, infection or disintegration of the material possibly causing extrusion or fistula formation, are avoided.

Targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent atrial fibrillation: Results of the RACE 3 trial

AimsnAtrial fibrillation (AF) is a progressive disease. Targeted therapy of underlying conditions refers to interventions aiming to modify risk factors in order to prevent AF. We hypothesised that targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent AF.nnnMethods and resultsnWe randomized patients with early persistent AF and mild-to-moderate heart failure (HF) to targeted therapy of underlying conditions or conventional therapy. Both groups received causal treatment of AF and HF, and rhythm control therapy. In the intervention group, on top of that, four therapies were started: (i) mineralocorticoid receptor antagonists (MRAs), (ii) statins, (iii) angiotensin converting enzyme inhibitors and/or receptor blockers, and (iv) cardiac rehabilitation including physical activity, dietary restrictions, and counselling. The primary endpoint was sinus rhythm at 1 year during 7 days of Holter monitoring. Of 245 patients, 119 were randomized to targeted and 126 to conventional therapy. The intervention led to a contrast in MRA (101 [85%] vs. 5 [4%] patients, Pu2009<u20090.001) and statin use (111 [93%] vs. 61 [48%], Pu2009<u20090.001). Angiotensin converting enzyme inhibitors/angiotensin receptor blockers were not different. Cardiac rehabilitation was completed in 109 (92%) patients. Underlying conditions were more successfully treated in the intervention group. At 1 year, sinus rhythm was present in 89 (75%) patients in the intervention vs. 79 (63%) in the conventional group (odds ratio 1.765, lower limit of 95% confidence interval 1.021, Pu2009=u20090.042).nnnConclusionsnRACE 3 confirms that targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent AF.nnnTrial Registration numbernClinicaltrials.gov NCT00877643.

35 years of experimental research in transmyocardial revascularization: what have we learned?

In the past 35 years many experimental studies have been performed to investigate the revascularization potential of transmyocardial revascularization and the possible working mechanisms underlying the observed clinical improvement in angina pectoris after this treatment. In this review of the experimental literature, the various methods that have been used to create transmyocardial channels and the most supported hypotheses on the working mechanism (channel patency, angiogenesis and myocardial denervation) are discussed and evaluated.

Varying the heart rate response to dynamic exercise in pacemaker-dependent subjects: effects on cardiac output and cerebral blood velocity

Cerebral blood flow increases upon the transition from rest to moderate exercise, but becomes affected when the ability to raise CO (cardiac output) is limited. HR (heart rate) is considered to contribute significantly to the increase in CO in the early stages of dynamic exercise. The aim of the present study was to test whether manipulation of the HR response in patients dependent on permanent rate-responsive ventricular pacing contributes to the increase in CO, MCA V(mean) [mean MCA (middle cerebral artery) velocity] and work capacity during exercise. The effect of setting the pacemaker to DSS (default sensor setting) compared with OSS (optimized sensor setting) on blood pressure, CO, SV (stroke volume) and MCA V(mean) was evaluated during ergometry cycling. From rest to exercise at 75 W, the rise in HR in OSS [from 73 (65-87) to 116 (73-152) beats/min; P<0.05] compared with DSS [70 (60-76) to 97 (67-117) beats/min; P<0.05] was larger. There was an increase in SV during exercise with DSS, but not with OSS, such that, at all workloads, SVs were greater during DSS than OSS. The slope of the HR-CO relationship was larger with DSS than OSS (P<0.05). From rest to exercise, MCA V(sys) (systolic MCA velocity) increased in OSS and DSS, and MCA V(dias) (diastolic MCA velocity) was reduced with DSS. No changes were observed in MCA V(mean). Manipulation of the pacemaker setting had no effect on the maximal workload [133 (100-225) W in OSS compared with 129 (75-200) W in DSS]. The results indicate that, in pacemaker-dependent subjects with complete heart block and preserved myocardial function, enhancing the HR response to exercise neither augments CO by a proportional offset of the exercise-induced increase in SV nor improves cerebral perfusion.

Transmyocardial laser channels

We present 2-dimensional echocardiographic images of laser-made channels in the myocardium in an experimental model and in a patient treated with transmyocardial laser revascularization.

Transmyocardial laser revascularisation and other treatment modalities for angina pectoris

Abstractu2002Ischaemic heart disease is one of the leading causes of morbidity and mortality in the western world. This paper provides an overview of the different treatments for one of the most common manifestations of ischaemic heart disease: angina pectoris. Besides the currently available conventional methods, several alternative treatments are described, with a special focus on transmyocardial laser revascularisation.

The old spontaneously hypertensive rat as a model for transmyocardial laser revascularisation research

Abstractu2002Animal models used in transmyocardial laser revascularisation (TMLR) research lack the increased fibrosis observed in patients with chronic myocardial ischaemia. This pathology has also been described in patients with chronic elevated afterload, and therefore we evaluated the spontaneously hypertensive rat (SHR) as a model for TMLR research. We compared (1) the myocardial pathology of SHR with the pathology of three TMLR patients, (2) the reaction to TMLR in SHR and human myocardium using three different lasers, and (3) myocardial hypoxia in SHR myocardium and (healthy) Wistar rat myocardium. SHR and human myocardium both showed increased fibrosis and a similar myocardial reaction to TMLR (comparable morphology of fibrotic TMLR channel scars). More hypoxic cells were observed in SHR than in Wistar control rat myocardium. The similarities between SHR and human chronic ischaemic myocardium make the SHR a suitable model for TMLR research.