35% of the volunteers were intensive care paramedics; 26% were paramedics; 20% were students; and 19% were other healthcare professionals.  

The proportion of volunteers who maintained compressions within the optimal range of 100 to 120 a minute, in compliance with 2010 guideline-compliant rates, was significantly higher when listening to Disco Science (82%) than when listening to Achy Breaky Heart (64%) by Billy Ray Cyrus, or no music at all (65%).

But over a third of compressions were still found to be too shallow, irrespective of the test method applied, and incorrect hand positioning was observed for over half to two thirds of all completed compressions.

  The authors conclude that, “considering the combined importance of correct depth and rate, [we] are unconvinced that music provides any benefit in improving the quality of CPR compared with a metronome or audible feedback, suggesting that that this interesting but unproductive area of resuscitation research should be discontinued”.

The Bee Gees’ song Stayin’ Alive has previously been advocated as a suitable tune in the US, while the children’s song, Nellie the Elephant had been thought to be the optimal musical accompaniment to aid the delivery of CPR in the UK.

  But it has since been discredited because while it helps to maintain a compression rate of 100 a minute, it doesn’t help to provide the right compression depth of 5 to 6 cm, say the authors.

References

1 Woollard M, Poposki J, McWhinnie B, Rawlins L, Munro G, O’Meara P.  Achy breaky makey wakey heart? A randomised crossover trial of musical prompts. Emerg Med J 2011. doi: 10.1136/emermed-2011-200187.

“Emergency physicians and Interventional Cardiologists told us that more definitive ECG information could help them identify high-risk cardiac patients more quickly, when seconds count,” stated Gerald McMorrow, founder and CEO of Verathon.

“By offering a 360° view of the electrical activity of the heart, Heartscape is designed to help healthcare providers assess the patients’ status faster and accelerate their treatment. We believe that with more accurate diagnosis, better outcomes and lower costs are the result,” he added.

A US introduction is anticipated in 2012, Verathon have said.

References:

1 Owens CG, McClelland AJJ, Walsh SJ et al. Prehospital 80-lead mapping: Does it add significantly to the diagnosis of acute coronary syndrome? J Electrocard. 2004/37(suppl): 223-32.

2 McClelland AJJ, Owens CG, Menown IBA, Lown M, Adgey AJJ et al. Comparison of the 80-lead body surface map to physician and to 12-lead electrocardiogram in detection of acute myocardial infarction. Am J Cardiol. 2003/92: 252-7.

3 Ornato JP, Menown IBA, Peberdy MA et al. Body surface mapping vs 12-lead electrocardiography to detect ST-elevation mycocardial infarction. Am J Emerg Med. 2009/27: 779-84.

Professor Riley’s team is looking at how the heart’s own cells might help to replace damaged muscle and blood vessels after MI.  They have recently shown, for the first time, that some adult heart cells have the capacity to repair damage if stimulated by the protein thymosin β4.¹

The Mending Broken Hearts Appeal was launched earlier this year. The charity hopes to fund £50 million of groundbreaking regenerative medicine research to help develop new treatments in as little as 10 years’ time.

Professor Riley said:  “We’re looking for ways to awaken the healing ability of the heart – and we’ve shown in mice that the heart has the potential to repair itself, if given the right stimulus. The next step is to find a way to achieve this in patients who have suffered a heart attack.

“This BHF Professor award gives me and my team the opportunity to use the resources and expertise here in Oxford, so that together we can make faster progress towards our goal of improving the lives of patients affected by debilitating heart failure – a condition that currently has no cure.”

Professor Peter Weissberg, Medical Director at the BHF, said:  “We’re delighted that Paul Riley is the first BHF Professor to be funded by our Mending Broken Hearts Appeal. He is leading the world in this field and we couldn’t have got off to a better start.  His move to Oxford, one of our Centres of Research Excellence, means he will join several other BHF-funded scientists searching for a way to heal damaged hearts. His research gives hope to hundreds of thousands of people in the UK who suffer from heart failure after a heart attack.”

Professor Riley takes up the new post of Chair of Development and Reproduction within the University of Oxford’s Department of Physiology, Anatomy and Genetics (DPAG). He will move with his research team, currently based at University College London, in October.

References

1 Smart N, Bollini S, Dubé KN, et al. De novo cardiomyocytes from within the activated adult heart after injury. Nature 474, 640–4. doi:10.1038/nature10188

For more information about the work of the BHF visit bhf.org.uk

Patients were followed up for a mean of 3.2 years.  Cases of non-fatal MI and deaths from CHD were compared, through a nested case-control analysis, in subjects who had discontinued treatment with those who had continued.

Compared with current users, people who had recently stopped taking low dose aspirin were at a significantly increased risk (60%) of non-fatal MI, irrespective of the length of time the patient had been taking low dose aspirin.  The authors emphasise that, for every 1,000 patients, there were about four extra cases of non-fatal MI over a one-year period among patients who recently discontinued compared with those who continued therapy.

Recent discontinuers of low dose aspirin were also at a significantly increased risk of non-fatal MI or death from CHD combined, but there was no increase in risk of CHD death alone in patients who discontinued treatment.

The authors assert that increasing adherence to low dose aspirin could have a major impact on the benefit obtained in the general population.  They call for further research to test whether efforts to encourage patients to continue prophylactic treatment with low dose aspirin will result in a decrease in non-fatal MI.

“These findings are important and support previous studies showing an increase in adverse events after aspirin withdrawal,” say experts from Italy in an accompanying editorial.² They say that, while the results of further studies are eagerly awaited, patients should be maintained on low dose aspirin for as long as possible, and advised never to discontinue the treatment unless explicitly instructed.

References

1 Rodríguez LAG, Cea-Soriano L, Martín-Merino E, Johansson S. Discontinuation of low dose aspirin and risk of myocardial infarction: case-control study in UK primary care.  BMJ 2011;343:d4094. doi: 10.1136/bmj.d4094.

2 Biondi-Zoccai G, Landoni G. Discontinuation of aspirin for secondary prevention. BMJ 2011;343:d3942 doi: 10.1136/bmj.d3942.

The researchers identified a new locus, ADAMTS7, which increased the risk of developing CAD. In the heart-attack comparison, the authors found a new association at the ABO blood group locus. They found that the same gene that codes for the enzyme behind people being blood group O offered protection against heart attacks.

They say: “Discovery of ABO as the top locus for myocardial infarction in patients with angiographic CAD is notable, in view of decades of work suggesting a relation between ABO blood-groups and both thrombosis and coronary heart disease.”

They conclude: “Our findings indicate that specific genetic variants predispose to the development of coronary atherosclerosis whereas others predispose to subsequent plaque rupture and acute heart attack… The relation to specific CAD phenotypes might modify how novel loci are applied in personalized risk assessment and used in the development of novel therapies for CAD.”

In a linked comment, Drs Luca A Lotta and Flora Peyvandi, Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, and Luigi Villa Foundation, University of Milan, Italy, say: “As in other genome-wide association studies, biological explanations for the identified associations are still not evident. The field of genetics is rapidly moving forward and large re-sequencing studies, with next-generation platforms, will probably compete with or even replace genome-wide association studies as the gold-standard for the identification of disease-related genes or variants. These studies might also provide insights into associations identified by genome-wide association studies.”

References

1. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies, Reilly, MP, et al. Lancet, 2011;377:383 – 392

Read Online: http://www.thelancet.com/ journals/lancet/article/ PIIS0140-6736(10)61996-4/abstract (payment/subscription required)

“The upcoming ESC Clinical Practice Guidelines for the management of STEMI, to be published in 2012 will address this issue on the basis of the Cochrane review and the entire literature,” said Gabriel Steg from Hôpital Bichat (Paris, France), co-chairman of the ESC Task Force on the management of AMI-STEMI.

Supplemental oxygen therapy, said Stefan James, also co-chairman of the ESC AMI-STEMI Task Force, is currently recommended in European guidelines for patients with desaturation hypoxia, but that there is no clear guidance about what to do for normotensive MI patients.

“The reality is that supplemental oxygen is given to virtually all patients in the early phase of an MI, whether in the ambulance, emergency department or whilst undergoing percutaneous interventions (PCI) in the cath lab,” said James, from Uppsala Clinical Research Centre (Sweden). “But following the publication of these two papers we need to consider whether it should be clearly stated that oxygen therapy is only appropriate for hypoxic patients.”

The JACC paper, by Raman Moradkhan and Lawrence Sinoway from Pennsylvania State University College of Medicine (USA), reviewed data examining the effects of supplemental oxygen in normoxic patients with acute CAD (1) . “Although the use of oxygen is clearly appropriate and advisable to treat hypoxia, we hypothesize that excessive use of supplemental oxygen in normoxic cardiac patients could potentially lead to worse outcomes in a number of patients,” wrote the authors. “We are not aware of any studies demonstrating that normoxic subjects undergoing percutaneous coronary intervention for acute myocardial infarction derive any benefit from supplemental oxygen.”

Indeed, the Cochrane meta-analysis found that nearly three times more deaths occurred among the patients who had been randomised to oxygen therapy compared those who had been given air, and that there were no benefits in terms of pain relief (2). The review by Juan Cabello, from the Hospital General Universitario de Alicante (Alicante, Spain),   had identified only three randomised controlled trials involving just 387 patients that compared outcomes for one group given oxygen and another given normal air.  “Because the trials had few participants and few deaths this result does not necessarily mean that giving oxygen increases the risk of death. The difference in numbers may have occurred simply by chance,” wrote the authors. “We think it is important to evaluate this widely used treatment in a large trial, as soon as possible, to make sure that current practice is not causing harm to people who have had a heart attack.”

A further issue, according to James, is that the studies mentioned in the Cochrane analysis are up to 30 years old and only one was appropriately blinded.   “Over the past few years we have completely changed the way MIs are managed. Before patients were automatically transferred to cath labs for PCI there was a much stronger rationale for giving people oxygen therapy because they were more likely to develop pulmonary congestion. But even in those circumstances there doesn’t appear to have been any mortality advantage among the group receiving oxygen.”

The current widespread use of oxygen by clinicians for MI is almost intuitive. “It’s widely known that an MI causes oxygen deficits in the heart muscle, so it seems logical to provide additional oxygen,” said James. “ However, the reality is that it doesn’t follow that if you increase inhaled oxygen you will automatically transfer oxygen to the heart. In fact, there’s data to show that oxygen is a vasoconstrictor and may therefore act to increase the damage caused by an MI.”

Mechanisms need to be put in place, James commented, to organise large scale randomised trials without the support of industry in areas where there are no new pharmaceutical agents involved. “One logical way forward is to perform trials in registries. Indeed, in Sweden we are currently evaluating thrombus aspiration in MI in our Sweetheart registry,” he said.

In the meantime until new guidelines are published, James’ advice to clinicians, nurses and ambulance staff, would be to avoid oxygen in acute MI patients, unless they have demonstrably low oxygen levels, and then to only deliver sufficient to avoid hyperopic.

References

1. Revisiting the Role of Oxygen Therapy in Cardiac Patients. R Mora khan, LI Sino way. JACC September 21 2010, 56: 1013-6
2. Oxygen therapy for acute myocardial infarction (Review) Cabello JB, Burls A, Emparanza JI, Bayliss S, Quinn T. The Cochrane Library 2010. Issue 6. DOI: 10.1001/14651858.CD007160.pub2.

“This study shows that as a country, we do a good job in treating patients with heart attack,” said John S. Rumsfeld, M.D., Ph.D., chief science officer and chair of the NCDR and acting national director of cardiology for the Veterans Affairs Health Administration. “More patients with heart attacks qualify for urgent angioplasty and stenting, and they are getting it quicker. There have also been improvements in giving recommended medications to heart attack patients—many of which reduce the risk of death and long-term complications.”

Equally impressive are the results for coronary angioplasty and stenting. These procedures, which fall under the umbrella term percutaneous coronary intervention (PCI), involve threading a slender tube into the arteries of the heart, expanding a tiny balloon to widen the artery and, usually, leaving an expandable metal stent in place to hold the artery open.

“We’re seeing lower complication rates with PCI, despite greater complexity in both the types of patients and the lesions,” said Matthew T. Roe, M.D., M.H.S., associate professor of medicine at Duke University Medical Center and the Duke Clinical Research Institute, Durham, NC. “In fact, the very nature of PCI is changing, with new medications and new stents used during procedures.”

For the study, researchers drew from two large NCDR registry programs. To characterize recent trends in treatment and outcomes of heart attack, they analyzed data from the ACTION Registry^®–GWTG™. The NCDR ACTION Registry-GWTG is a partnership between the ACC and the American Heart Association and includes data on the hospital care of patients with two types of heart attack known as STEMI and NSTEMI. The resulting study group consisted of all 131,980 patients treated for a heart attack at approximately 250 participating hospitals from January 2007 through June 2009.

The data analysis showed significant improvements in several key aspects of heart attack care, including:

• Increase from 90.8 percent to 93.8 percent in the use of treatments to restore blood flow to the heart in patients with STEMI heart attacks.
• Increase from 64.5 percent to 88 percent in the number of patients with STEMI heart attacks treated with PCI within 90 minutes of arriving at the hospital—a key quality benchmark.
• Improvement from 89.6 percent to 92.3 percent in overall performance scores that measure timeliness and appropriateness of therapy for STEMI heart attacks.
• Improvement in achieving correct dosing of several types of “blood thinners” among NSTEMI patients.
• Reduction from 6.2 percent to 5.5 percent in risk-adjusted hospital death rates among STEMI patients and from 4.3 percent to 3.9 percent among NSTEMI patients.

Improvement in prescribing guidelines-recommended medications, including aspirin, clopidogrel, statins, beta blockers and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, as well as in counseling patients to stop smoking and referring patients to cardiac rehabilitation.

Patients are also taking important steps toward improving heart attack care by heeding the warning signs of heart attack, the data reveal. The time from the beginning of heart attack symptoms to the patient’s arrival at the hospital dropped significantly during the study period, from 1.7 hours to 1.5 hours, on average.

“Patients are coming to the hospital sooner,” Dr. Rumsfeld said. “That shows a greater awareness by the public that if you have unexplained chest pain or shortness of breath, you need to get to the hospital quickly. The sooner you get treatment for a heart attack, the better your chances of survival and the less likely you are to experience long-term complications like heart failure.”

To evaluate PCI trends, investigators analyzed data from the NCDR CathPCI Registry^® database, which contains hospital data on diagnostic cardiac catheterization and PCI. It is a partnership between the ACC and the Society for Cardiovascular Angiography and Interventions. The resulting PCI study group consisted of all 1,708,247 patients who had PCI from January 2005 through June 2009. During that time, participating hospitals grew from 436 to 959.

The data analysis revealed several notable trends, including:

Increase in procedural complexity, including treatment of significantly more patients with challenging “type C” lesions.

Reduction in complications related to bleeding or injury to the arteries used for passing tubes to the heart.

Changes in the use of medications designed to prevent unwanted blood clots, reflecting the results of recent clinical trials and recommendations from new clinical practice guidelines.

Reduction in the overall use of drug-eluting stents, partially balanced by increased use of new types of drug-eluting stents.

In addition to its encouraging findings, the analysis also highlights specific areas in need of improvement and identifies targets for future research, particularly those aimed at reducing the bleeding risk associated with even the best therapies.

Moreover, the analysis highlights the value of clinical registries themselves and the unique information they provide. Insurance databases document how many patients had a particular diagnosis or procedure, while randomized clinical trials test therapies under tightly controlled circumstances and in narrowly defined groups of patients. But the information from the NCDR documents the cardiovascular treatments average patients receive every day, and how those treatments affect their health. In short, it helps doctors give better cardiovascular care in daily practice.

“This is direct clinical data from doctors and hospitals themselves on which patients got which treatments and how they did,” Dr. Rumsfeld said. “If you want to actually understand the risk of a given patient and match the best treatment to their situation, you need real clinical data.”

The NCDR also helps hospitals and cardiologists to achieve the highest quality of care, by allowing them to compare their treatments and clinical outcomes against those of similar volume and size across the nation. Patients who understand the value of clinical registries can be advocates for improving healthcare quality in their communities.

“Educated consumers can stimulate improvements in their community,” Dr. Roe said. “If your hospital is not participating in the NCDR and other clinical registries, you should ask, ‘Why not? What are you doing to respond to and collect data that will allow you to take better care of your patients?’”

Notes

CDR is an initiative of the American College of Cardiology Foundation^®, with partnering support from the following organizations: CARE Registry—The Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, American Academy of Neurology, American Association of Neurological Surgeons/Congress of Neurological Surgeons, and Society for Vascular Medicine; CathPCI Registry—The Society for Cardiovascular Angiography and Interventions; ICD Registry—Heart Rhythm Society; IMPACT Registry—The Society for Cardiovascular Angiography and Interventions and American Academy of Pediatrics; IC³ Program—MedAxiom and Spirit of Women; ACTION Registry–GWTG— An initiative of the American College of Cardiology Foundation and the American Heart Association, with partnering support from Society of Chest Pain Centers.

“This study provides excellent ammunition both to convince patients about the benefits of reducing their individual salt intakes and also to persuade the EU of the urgent need to introduce legislation to restrict the salt content of  processed foods,” said ESC spokesman Professor Frank Ruschitzka, a cardiologist and hypertension specialist from the University of Zurich, Switzerland.

“This study represents the evidence that a reduction of salt intake not only lowers blood pressure but also prevents cardiovascular events. The case for population-wide salt reduction is now compelling,” he added.

In the paper, Kirsten Bibbins-Domingo and colleagues, from the University of California, San Francisco, USA, undertook a computer simulation showing the effects of population wide reductions of dietary salt intakes in all adults aged 35 to 85 years in the USA.   Reducing  dietary salt intake by 3 g per day (1200mg less sodium per day) could result in 60,000 to 120,000 fewer cases of heart disease , 32,000 to 66,000 fewer strokes and 54,000 to 100,000  fewer heart attacks.

A reduction in dietary salt of 3g per day, the authors went on to say, would have approximately the same effect on reducing cardiac events as a 50 % reduction in tobacco use, a 5% reduction in body mass index among obese adults or the use of statins to treat people at low or intermediate risk for CHD events.  Furthermore, reducing dietary salt intakes by 3g per day would save  $10 billion to $ 24 billion in annual health care costs.

ESC spokesperson Professor Giuseppe Mancia,  from the University of Milano-Bicocca, St. Gerardo Hospital (Milan, Italy), said the annual health cost savings outlined in the study would be likely to prove a persuasive argument for both the EU and individual European governments.

Recent studies clearly show that salt reduction reduces cardiovascular deaths.⁴ Epidemiological studies have also firmly established that increased intakes of salt directly increase blood pressure.  High salt intakes are believed to exert their detrimental effects by influencing fluid retention, which in turn increases blood pressure. “But it’s important for patients to appreciate that not all cardiovascular problems relating to salt are mediated through hypertension. Salt can have an adverse effect on cardiovascular health, even among people with normal blood pressure,” said Ruschitzka.

Salt intakes across Europe are known to vary widely, ranging from 8.6 g of salt per day  in the UK, to around 12 g salt in Croatia. Even the best intakes, however, are falling  widely short of the  ESC Clinical Practice Guidelines for the Management of Arterial Hypertension (2) , based on WHO data, that recommend that only 5g of salt should be consumed  per day. This amounts to just one teaspoonful.

While individuals may use salt sparingly at home, around 75 % of the salt we eat is already in the food we buy. This, says the ESC, underlines the need for legislation to lay down guidelines. “The reality of international food production in Europe means that such public health initiatives need to be tackled on a European wide basis, rather than an individual country basis,” said Ruschitzka.

Furthermore, added Mancia, concerted action is usually more effective. “It has the advantage of preventing country to country inequalities and furthermore prevents the reinvention of the wheel in each individual country,” he said.

But calls for legislation do not mean that physicians should stop their efforts to  persuade patients to introduce individual changes in lifestyle. Patients, they stress, need to be taught about the importance of reducing salt in their cooking and also for the need to check food labels. People need to learn to appreciate that the salt contents can vary widely even in the same product. Take bread, for example. Recent research from Consensus Action on Salt and Health (CASH, a charity lobbying food manufacturers in the UK) has shown that the highest salt content was 3g salt per 100 g of bread, while the lowest was 0.7 g salt per 100g.

To improve cardiovascular health, salt reduction cannot be undertaken in isolation. “It needs to be remembered that lifestyle measures such as smoking cessation, weight reduction, increased physical exercise, and eating plenty of fruit and vegetables are also important for reducing cardiovascular disease,” said Mancia.

Salt was again on the agenda with World Salt Awareness Week 2010 , (February 1- 7) (3).  The week was run by World Action on Salt and Health (WASH), a global group that works with governments  to highlight the need for widespread introduction of population based salt reduction strategies.

Much can be done to reduce salt intakes through public health policy, say WASH.  They cite the success of Consensus Action on Salt and Health (CASH),  launched in 1996 to encourage  food manufacturing companies in the UK to make voluntary reductions in their  salt content. Since the start of the policy salt intakes among UK adults (calculated from 24-hour urine samples) have fallen from 9.5 to 8.6 g per day.

In July 2009, WASH surveyed over 260 food products available around the world from food manufacturers such as KFC, McDonalds, Kellogg’s, Nestle, Burger King and Subway, finding surprisingly wide spread variations. For example, Kellogg’s All Bran for sale in France, Norway, Sweden and the Netherlands contains 1.30 g salt per 100 g compared to salt levels of 0.65 g per 100g for the product in the US. Such data underlines the urgent need to eradicate country to country inequalities, and bring everyone up to the highest possible standards.

“The paper by Bibbins-Domingo and colleagues is an urgent call to action. Policy makers in the European Community need to implement public health interventions that result in reductions in salt intake now. Reducing the salt content of our unneccesarily oversalted ,processed food is an inexpensive, yet highly effective public health intervention that we can’t afford to miss,“ concluded Ruschitzka.

References

1. Bibbins-Domingo K, Glenn CC, Coxson PG et al. Projected Effect of Dietary Salt Reductions on Future Cardiovascular Disease.  New Engl J Med. 2010 published on line on 20 January 2010 (10.1056/NEJMoa0907355)
2. http://www.escardio.org/guidelines-surveys/esc-guidelines/Pages/arterial-hypertension.aspx
3. www.worldactiononsalt.com
4. Pasquale Strazzullo, Lanfranco D’Elia, Ngianga-Bakwin Kandala, and Francesco P Cappuccio.  Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ 2009;339:b4567, doi: 10.1136/bmj.b4567 (Published 24 November 2009)

The MADIT-CRT study was a randomised trial designed to determine if CRT-D therapy would reduce the primary endpoint (all-cause mortality or heart failure events, whichever occurred first) when compared to patients receiving ICD-only therapy. The study population involved cardiac patients in New York Heart Functional Class I or II (no or mild symptoms) who had either ischaemic or non-ischaemic heart disease with left ventricular dysfunction (ejection fraction <30%) and QRS duration of >130ms on ECG.

Cardiac resynchronisation therapy (CRT) with or without a defibrillator is indicated for use in patients with severe heart failure (New York Heart Association Class III/IV), and CRT has been shown to reduce symptoms, mortality and hospitalisation in very sick cardiac patients. The question that remained was whether CRT would improve heart function and slow or prevent the development of heart failure in the less severe NYHA class I/II cardiac patients (moderately high risk, but with no or mild symptoms) by intervening early in the course of the disease before the development of advanced symptoms.

The MADIT-CRT trial enrolled and followed 1820 patients from 110 centers in Europe, Canada, and the USA during a 4.5-year period between December 2004 and 22 June 2009, when the trial was officially ended because of the superiority of the cardiac resynchronisation therapy (p=0.001). Patients were randomised in a 3:2 fashion to receive either CRT-D or ICD alone, and all patients received optimal medical therapy for heart failure during the trial.

The superiority of CRT-D therapy was found to be present in all patient sub-groups, including those with ischaemic and non-ischaemic types of heart disease, as well as in males and females, younger and older patients, and those with mild and more advanced heart dysfunction.

Commenting on the results, the study’s principal investigator, Professor Arthur J Moss from the University of Rochester Medical Center, New York, USA, said: “Cardiac resynchronisation therapy was dramatically effective in this large study population, with a 34% reduction in the risk of all-cause mortality or heart failure. The benefit is dominated by a 41% reduction in heart failure events. This results validate a new indication for cardiac resynchronisation therapy in the prevention of heart failure in at-risk asymptomatic or mildly symptomatic cardiac patients. It seems likely that this preventive CRT-D therapy will have widespread application and utilisation.”

Cardiac Resynchronisation Therapy: Reverse Trial

Cardiac resynchronisation therapy (CRT) is a proven therapy indicated for patients with moderate to severe heart failure. Additional 24-month clinical data presented at the Barcelona ESC Congress on the European cohort of 262 patients in the REVERSE (Resynchronisation Reverse Remodeling in Systolic Left Ventricular Dysfunction) trial, sponsored by Medtronic, Inc., provides a deeper understanding of how CRT improves the function of the heart, including reduction in heart size and improvements in pumping efficiency, in certain heart failure patients with mild symptoms.

With 610 patients studied, REVERSE is the first large-scale, global, randomized, double-blind trial to demonstrate the impact of CRT in mild heart failure patients or asymptomatic patients who previously had heart failure symptoms. As previously reported, the trial did not meet statistical significance for its primary endpoint – a heart failure Clinical Composite Score (a measure of both subjective and objective assessments) at 12 months. However, the European cohort, which was followed through 24 months, did demonstrate statistical significance.

Three sessions featuring 24-month REVERSE data were presented during the European Society of Cardiology congress in Barcelona:

• Clinical Trial Update: “Cardiac Resynchronisation Therapy Induces Major Structural and Functional Reverse Remodeling in Mild Heart Failure,” by Dr. Stefano Ghio of Policlinico San Matteo in Pavia, Italy.
• “CRT in Mild Heart Failure: Differences in Outcomes Between NYHA Class I and II Patients Over 24 Months of CRT,” by Prof. Cecilia Linde of Karolinska University Hospital in Stockholm.
• “Relationship of QRS Duration to Reverse Remodelling with CRT in Mild Heart Failure Over Two Years,” by Michael Gold, M.D. of the Medical University of South Carolina in Charleston, S.C.

“The REVERSE 24-month results, presented at ACC 2009, suggest that CRT may improve clinical outcomes and ventricular function,” said Prof. Ghio. “While we’ve already seen improvement in more symptomatic patients with CRT, the additional analyses presented here at ESC give us valuable insights about ventricular structure and how CRT might be used to modify disease progression and help heart failure patients with mild symptoms.”

Key Findings

Additional 24-month results from the European cohort of the REVERSE trial indicate that CRT may prevent or slow the progression of disease in asymptomatic or mildly symptomatic heart failure patients.

• CRT reduced the need for heart failure hospitalisation in NYHA Class II patients (p=0.004) (Linde).
• The trial demonstrated a statistically significant reduction in heart size (left ventricular end systolic volume index, or LVESVi), as measured by cardiac ultrasound, improving its function and helping the heart pump more efficiently in patients receiving CRT (p<0.0001). This trend was first seen at 12 months, and continued at 24 months (Ghio).
• There was a statistically significant increase in LVEF: from 28.1 percent to 34.8 percent in patients receiving CRT, compared to 27.8 percent to 29.9 percent in patients not receiving CRT (p=0.002) (Ghio).
• CRT reduced left ventricular volumes throughout the range of QRS duration (the length of time for the heart to contract) (p<0.0001), and CRT effectiveness was greater as QRS duration widened (Gold).

Currently, CRT is not approved in the United States for use in the mildly symptomatic or asymptomatic patients who were shown to benefit from CRT in this trial.

Trialists believe that the REVERSE trial continues to uncover valuable data for the clinical community to inform the treatment of heart failure patients.

PreSCD II registry shows mortality reduction after non-acute ICD implantation in myocardial infarction survivors

The goals of the PreSCD II (Prevention of Sudden Cardiac Death II) registry are to collect recent data on patients with high risk for sudden cardiac death after a heart attack and to describe their prognosis in relation to initial left ventricular ejection fraction (LVEF) as the primary risk marker.

Findings from the latest PreSCD II analysis show that patients protected against sudden cardiac death by an implantable cardioverter defibrillator (ICD) one month or more after MI showed a non-significant (p=0.053) 44% lower mortality than comparable patients without an ICD. In those patients with severely reduced heart function (ejection fraction of 30% or less) mortality was reduced by 47%, with borderline significance (p=0.07). “Remarkably,” says investigator Professor Heinz Völler from the Klinik am See in Ruedersdorf, Germany, “we observed in the data a survival benefit that increased with the time interval between MI and ICD implantation.”

Based on the MADIT II trial results, ejection fraction is predominantly used for risk stratification in MI patients to determine implantation of an ICD. The PreSCD II analysis was thus stratified according to patients who presented with a severely reduced ejection fraction (≤30%), a moderately impaired (31-40%) or normal heart function. “We were surprised that in the high risk group of patients with severely reduced heart function, which comprised only 2.5% of the registry population, only 22% of them were protected by an ICD as primary prevention of sudden cardiac death,” said Professor Völler.

Between December 2002 and May 2005 the PreSCD II registry enrolled 10,612 MI survivors in 19 rehabilitation centres in Germany. Left ventricular function was determined in all patients one month or later after the index infarction, thus evaluating the risk for sudden cardiac death. All patients with a reduced ejection fraction of ≤40% plus a random sub-sample of the patients with preserved EF (n = 2058) were observed for at least 36 months for clinical events and mortality.

Commenting on the results, Professor Völler said: “Patients who survive myocardial infarction have an increased risk for sudden cardiac death. Randomised controlled trials like MADIT II and SCD-HeFT showed that patients with impaired left ventricular function are particularly protected against sudden cardiac death by an implantable defibrillator. All-cause mortality was reduced up to 31% by the ICD. However, in these trials the ICD was predominantly implanted several months after acute Mi. Other trials like DINAMIT and IRIS failed to demonstrate an ICD benefit if implanted early after myocardial infarction. International guidelines on anti-arrhythmic therapy reflect these results.

“The PreSCD II registry has confirmed the findings of the randomised clinical trials in a real life environment, where ICD implantation rates were lower than suggested by study results and guidelines. Noteworthy in this registry was an increasing reduction of mortality over time, depending on the time interval between index infarction and ICD implantation. However, when interpreting the data, it should be remembered that registry analyses do not in general have the confirmative power of a randomised controlled trial with causal connections.”

References

The PreSCD II registry was endorsed by the German Society of Cardiology (DGK) and the German Society for Prevention and Rehabilitation (DGPR), and supported by a grant from Boston Scientific Medizintechnik GmbH, Germany.

Results from the European CRT Survey

The European cardiac resynchronisation therapy (CRT) Survey is a joint initiative taken by the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology. Its primary objective is to describe current European practice and routines associated with the implantation of a CRT device with or without an ICD (implantable cardioverter defibrillator) capability in patients with heart failure.

The data collected from the survey provide useful information in CRT for heart failure on patient demographics and selection, clinical characteristics, diagnostic criteria, implantation routines and techniques, short-term outcomes, adverse experience, and assessment of adherence to guideline recommendations. These data should be useful for benchmarking individual patient management and national practice against wider experience. The data from randomised trials of CRT are limited and based largely on selected patients at high-volume centres with experienced operators. In contrast, the European CRT Survey describes current routine practice in CRT implantation based on a wide range of sampling.

Data were collected between 1st November 2008 and 30th June 2009 from 140 volunteer centres in 13 countries (Austria, Belgium, France, Germany, Ireland, Israel, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, UK). Information was provided on consecutive patients successfully implanted with a CRT device with or without an ICD (CRT-P, CRT-D). All patients agreeing to participate will have a follow-up visit approximately one-year after CRT implantation.

Findings

The survey enrolled 2438 patients, with a mean age of 68 years (31% were 75 years or older). There are characteristic differences between those receiving CRT-P and CRT-D; the reasons are many, but it is clear that demographic and economic factors play a part. However, the Survey data show that younger patients, men and those with ischaemic aetiology are more likely to receive a CRT-D device.

The data also show that the cohort is remarkably similar to the cohorts recruited in randomised clinical trials (with a low proportion of women receiving CRT). However, patients in the Survey were older, and more frequently had mild symptoms. A substantial number had a narrow QRS complex (although a broadening is a typical finding in many trials) and more frequently had atrial fibrillation. However, in this real-world population, complication rates were similar to those reported in the randomised trials.

Says lead author Dr Nigussie Bogale from Stavanger University Hospital in Norway: “This European CRT Survey represents a reasonably large sample reflecting current European practice in the use of CRT devices in the management of patients with heart failure. Our findings show that many patients who do not strictly conform to current guideline recommendations frequently receive a CRT device. Clinicians, researchers and healthcare providers should find these data useful in designing strategies for patient management, trial design and resource allocation.”

It is unclear what chemical component of particulate matter (PM) is responsible for these adverse cardiovascular effects, but smaller size PM appears to be more strongly correlated. Further difficulties in assessing exposure arise when data are derived from fixed monitoring stations because of differences between outdoor and indoor PM pollution, the latter of which often is the more relevant.

Systemic inflammation and prothrombotic conditions that are elicited by PM in the lung are thought to represent the underlying mechanism of cardiotoxicity, but other mechanisms have been inferred, whereby inflammation and thrombosis may simply co-exist.

Personal exposures to PM₁₀, PM_2.5, and PM_0.25, was measured over 24 h in 39 patients (36 males, 3 females, mean age 60.3 years), with prior myocardial infarction (> 6 months). Simultaneously, a 24 h ECG was recorded and then analysed for heart rate variability (HRV) and ventricular arrhythmias. Breath condensate and blood samples also were collected at the end of monitoring to measure several indexes of inflammation. Negative correlation was found between HRV and exposure to PM_0.25 in a group of patients not taking ß-blockers. More severe ventricular arrhythmias were observed at the highest concentrations of PM₁₀ and PM_2.5. Indexes of inflammation in either breath condensate or blood did not correlate with PM exposures.

The study shows that exposure to ultrafine particles is associated with autonomic dysregulation in selected patients with myocardial infarction. More severe arrhythmias occur at the highest exposure to large particles. Nevertheless, the underlying mechanisms remain hypothetical because inflammation may be evoked by PM or be related to the disease itself, these workers conclude.

Reference:

Individual exposure to particulate matter and the short-term arrhythmic and autonomic profiles in patients with myocardial infarction. Folino F, Scapellato L, Canova C, et al. European Heart Journal (2009) 30, 1614-1620.