Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Researchers document post-transplantation mortality rates in adults with congenital heart disease
Davies R. Circulation. 2011;123;759-767.

Following a high short-term mortality, patients with congenital heart disease had better late survival after heart transplantation, according to researchers.

The study involved 41,849 patients older than 18 years who were listed for primary transplantation between 1995 and 2009. Investigators compared patients with a history of congenital heart disease (CHD; n=1,035) with those with non-CHD causes (n=40,814). Of the study patients, 26,055 reached transplantation, with 10,484 having and 15,571 not having prior sternotomy.

According to study data, survival was comparable between CHD and non-CHD arms, although among CHD patients, mechanical ventricular assistance was not linked with superior survival to transplantation. Also reported among CHD patients was a higher likelihood of having a BMI of less than 18.5 at transplantation, fewer comorbidities and a younger age.

Researchers looked at early mortality rates and found a significantly higher rate among patients with CHD in both the reoperation arm (18.9% vs. 9.6%; P<.0001) and the non-reoperation arm (16.6% vs. 6.3%; P<.0001), despite a nearly equal mortality rate at 10 years (CHD, 53.8% vs. non-CHD, 53.6%).

In the study’s clinical perspective, the researchers wrote that improving the understanding of the differences between CHD and non-CHD patients may enable improvements in the outcomes of this increasingly important population.

“The increasingly common transplantation of patients with complex CHD may result in particularly high post-transplantation mortality, and centers performing these transplantations should proceed with caution,” they said. “Collection of data specific to the CHD population, including accurate congenital diagnoses, is essential to better understand and improve the outcomes with transplantation in this population.”

The paper by Davies and colleagues is a significant review of over 1,000 congenital heart disease patients who develop advanced HF that requires cardiac transplantation. This is the first look into these patients in a large registry from the United Network for Organ Sharing. It is noteworthy that patients with CHD are living longer and as many as 10-20% of CHD patients will eventually require cardiac transplantation. As seen in previous smaller studies, early mortality after transplant is high but it is comforting to know (from this study) that late survival is better than that among non-CHD patients. The CHD patients are, in general, younger and I believe they are more resilient to recover from complications. A major limitation from this study is that the specific CHD abnormality was not available through the UNOS Registry. Therefore, accurate outcomes of specific CHD diagnoses was not possible to determine. This will be important for future studies as specific CHD diagnoses may have different outcomes.
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Registry data highlight importance of clinical conditions in treating CTO lesions

Cardiovascular Research Technologies 2011
Cardiovascular Research Technologies 2011

New one-year data from the IRCTO registry have suggested that outcome of treatment of chronic total occlusion lesions was related to patient clinical conditions as opposed to strategy of treatments in Italy where prevalence of these lesions is roughly 12%.

According to presenter Alfredo R. Galassi, MD, director, Diagnostic and Cardiovascular Interventional Laboratory, Ferrarotto Hospital University, Catania, Italy and investigator on the trial, the incidence and prevalence of coronary chronic total occlusion [CTO] lesions, as well as the demographic characteristics of patients affected by CTO’s, are unknown.

“The aim [of the study] was to assess the prevalence, demographics, clinical characteristics and therapeutic strategy of patients with CTOs in order to improve the management of patients with chronically occluded coronary arteries,” he said.

The study included 1,777 patients from 12 centers throughout Italy from the Italian Registry on Chronic Total Occlusion (IRCTO). The patients had at least one CTO in a main coronary artery for greater than 3 months duration with vessel size greater than >2.5 mm at coronary angiography.

Overall, investigators reported 1,968 CTOs among patients. One month unadjusted clinical outcome did not result in a statistically significant difference in death, stroke or MI, among patients treated with percutaneous coronary intervention, CABG or optimal medical therapy. However, at 12 months, compared with optimal medical therapy, rates of death and acute MI but not stroke were significantly less in patients treated with PCI.

According to univariate analysis, predictors of hard events included ejection fraction <35% (OR=1.76; 95% CI, 1.12-2.77), multivessel disease (OR=2.07; 95% CI, 1.13-3.80) and age (OR=1.06; 95% CI, 1.04-1.08).

Additionally, concluded Galassi, patients with a successful PCI had a better outcome than those without one (P=.03). – by Brian Ellis

For more information:
Galassi A. Presented at: Cardiovascular Research Technologies 2011. Feb. 27-March 1, 2011; Washington, D.C. .

There is now a remarkable consistency from data from Italy. In fact, this represents, by my count, the 12th study that would suggest through indirect comparison and minding the biases both with regard to treatment and selection of these patients that there is a consistency across these observational studies demonstrating improved survival and freedom from adverse events over an immediate long-term follow-up—follow-up, in some observation studies, that extends now beyond many years.

That said, however, we still need a large randomized trial that would help refine the benefit of CTO revascularization from hard clinical endpoints. However, to design a trial based on hard clinical endpoints like mortality, you have to think about the limitations of sample size and statistical power. And probably what is more relevant is a composite that would reflect not only mortality in itself but avoidance of future ischemic events and rehospitalization and very importantly a benefit with regard to quality of life.

It is noteworthy, however, that in this Italian registry there is a lower representation of patients with multivessel disease and patients with reduced left ventricular function in part reflecting clinicians’ discretion to refer patients to surgery or to treat them with medical therapy alone. But it’s important to realize that these are some of the patients who derive the greatest relative treatment effect from CTO revascularization.

[Chevychelov]

FDA approves azilsartan medoxomil tablets for hypertension treatment

The FDA today announced the approval of azilsartan medoxomil, an angiotensin II receptor blocker, for the treatment of hypertension in adults.

Azilsartan medoxomil tablets (Edarbi, Takeda Pharmaceuticals) will be made available in 80 mg and 40 mg doses. The agency approved the drug based on data from more than 5,900 patients showing that azilsartan medoxomil was more effective at lowering 24-hour BP than valsartan (Diovan, Novartis) and olmesartan (Benicar, Daiichi Sankyo).

The 40 mg dose, according to a press release, will be available for patients taking high-dose diuretics.

“High BP is often called the ‘silent killer’ because it usually has no symptoms until it causes damage to the body,” Norman Stockbridge, MD, PhD, director of the Division of Cardiovascular and Renal Drugs Products at the FDA’s Center for Drug Evaluation and Research, said in the press release. “High BP remains inadequately controlled in many people diagnosed with the condition, so having a variety of treatment options is important.”

The boxed warning that accompanied azilsartan medoxomil specified that the drug not be used in pregnant women during the second or third trimester.
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Stroke and death rates similar in stenosis patients undergoing stenting or endarterectomy
Silver F. Stroke.2011;42:675-680. S

Researchers have found no significant difference in stroke and death rates in patients with carotid stenosis treated with carotid artery stenting or with carotid endarterectomy; however, periprocedural stoke and death rates were much lower in symptomatic patients who received stents.

The Carotid Revascularization Endarterectomy Vs. Stenting Trial (CREST) was a randomized endpoint trial that compared the safety and efficacy of carotid artery stenting (CAS) vs. carotid endarterectomy (CEA) in patients with high-grade carotid stenosis. The study was supported by the National Institute of Neurological Disorders and Stroke and the NIH, with additional funding from Abbott Vascular Solutions Inc.

Patients were defined as symptomatic if they exhibited relative symptoms up to 180 days of randomization. A total of 1,321 symptomatic patients and 1,181 asymptomatic patients were enrolled at 117 sites throughout the United States and Canada. The primary endpoint included stroke, MI, death within the periprocedural period or ipsilateral stroke within 4 years.

Operators included surgeons who performed 12 or more CEAs per year; interventionalists were experienced in CAS and received hands-on training using the stenting and embolic-protection devices being observed in the study.

In both arms, the periprocedural aggregate of stroke, MI and death were similar (5.2% vs. 4.5%; HR=1.18; 95% CI, 0.82-1.68). The stroke and death rate was higher for CAS than for CEA (4.4% vs. 2.3%; HR=1.90; 95% CI, 1.21-2.98). For symptomatic patients, the periprocedural stroke and death rates were 6 ± 0.9% for CAS and 3.2 ± 0.7% for CEA (HR=1.89; 95% CI, 1.11-3.21). For asymptomatic patients, stroke and death rates were 2.5 ± 0.6% for CAS and 1.4 ± 0.5% for CEA (HR=1.88; 95% CI, 0.79-4.42). Rates were lower in patients aged younger than 80 years.

“CREST has demonstrated that, with experienced surgeons and interventionalists, both CEA and CAS are viable options for carotid revascularization because the overall complication rates for both procedures are within current treatment guidelines,” researchers wrote.
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Low, high BMI increased mortality in Asians
Zheng W. N Engl J Med. 2011;364:719-729.

A study involving more than 800,000 East Asians has shown that both low and high BMI increased the likelihood of death from any cause, as well as cause-specific death.

However, researchers looked at nearly 300,000 Indians and Bangladeshis and found that only low BMI elevated the risk for death.

The more than 1.14 million participants who comprised the study were recruited in 19 Asian cohorts. Investigators defined 10 BMI levels, ranging from lowest (≤15) to highest (>35) and carried out pooled analyses of individuals to determine the association between BMI (mean 22.9 ± 3.6) and mortality risk.

During a mean follow-up of 9.2 years, approximately 120,700 cohort members died, with CVDs reported as the main cause of death (35.7%), followed by cancer (29.9%). For East Asians, or those from China, Japan or Korea, the lowest risk for death was among those with a BMI between 22.6 and 27.5. The risk was elevated for those with a BMI of 15 or less by a factor of 2.8 and for those with a BMI of more than 35 by a factor of 1.5.

For the cohorts composed of Indians and Bangladeshis, the risk for death from any cause was increased among those with a BMI of 20 or less vs. those with a BMI between 22.6 and 25, but not for those with a higher BMI.

“Overall, the risk of death among Asians, as compared with Europeans, seems to be more strongly affected by a low BMI than by a high BMI,” the researchers concluded. “Given the limitations of the current study, in which the risk of death was used as the outcome, additional studies are needed to quantify the association between BMI and the incidence of disease, in order to better define BMI criteria for overweight and obesity in Asians.” – by Brian Ellis

This is an interesting study. The “obesity paradox“ in Western countries is already known. Although obesity is a risk factor for diabetes, hypertension, CAD and premature death, in the systolic HF (stage C ) population, higher BMI is associated with a better prognosis. Similarly, in patients undergoing CABG, higher BMI is associated with a better prognosis. Cardiac cachexia (increased tumor necrosis factor-alpha) is associated with poor prognosis in systolic HF and in cancer.

Based upon my personal knowledge about Asian Indians, Bangladeshis and Pakistanis, the life expectancy is lower due to a variety of causes in urban people. In rural areas, even though the people are thinner, they live longer. I think lifestyles play an important role in regulating BMI in every country.

[Chevychelov]

Long-Term Implications of Cumulative Right Ventricular Pacing Among Patients With an Implantable Cardioverter-Defibrillator
Barsheshet A, Moss AJ, McNitt S, et al.
Heart Rhythm 2011;8:212-218.
Study Question: Does the burden of right ventricular (RV) pacing impact long-term survival in patients with implantable cardioverter-defibrillators (ICDs) placed for primary prevention?

Comparison of Voltage Map-Guided Left Atrial Anterior Wall Ablation Versus Left Lateral Mitral Isthmus Ablation in Patients With Persistent Atrial Fibrillation
Pak HN, Oh YS, Lim HE, Kim YH, Hwang C.
Heart Rhythm 2011;8:199-206.
Study Question: Is mitral isthmus (MI) block achieved more effectively by voltage-guided left atrial anterior wall (LAAW) radiofrequency ablation (RFA) than by left lateral mitral isthmus (LLMI) ablation?

National Trends in Utilization and Postprocedure Outcomes for Carotid Artery Revascularization 2005 to 2007
Eslami MH, McPhee JT, Simons JP, Schanzer A, Messina LM.
J Vasc Surg 2011;53:307-315.
Study Question: What are the trends in utilization, mortality, and stroke after carotid angioplasty and stenting (CAS) and carotid endarterectomy (CEA) from 2005 to 2007?

Impact of Early Surgery on Survival of Patients With Severe Mitral Regurgitation
Samad Z, Kaul P, Shaw LK, et al.
Heart 2011;97:221-224.
Study Question: Is there an association between the timing of surgery and long-term survival in patients with severe degenerative mitral regurgitation (MR)?

Relationship Between Left Ventricular Mass, Wall Thickness, and Survival After Subaortic Septal Myectomy for Hypertrophic Obstructive Cardiomyopathy
Brown ML, Schaff HV, Dearani JA, Zhuo L, Nishimura RA, Ommen SR.
J Thorac Cardiovasc Surg 2011;141:439-443.
Study Question: Following septal myectomy, do measures of left ventricular (LV) wall thickness (WT) and LV mass impact late survival in patients with hypertrophic cardiomyopathy (HCM)?

β-Blockade With Nebivolol for Prevention of Acute Ischemic Events in Elderly Patients With Heart Failure
Ambrosio G, Flather MD, Bohm M, et al.
Heart 2011;97:209-214.
Study Question: Does nebivolol, a beta-blocker with B-1 selectivity and nitric oxide modulating properties, reduce ischemic events in elderly patients with heart failure (HF)?

Progestogen-Only Contraceptives and the Risk of Acute Myocardial Infarction: A Meta-Analysis
Chakhtoura Z, Canonico M, Gompel A, Scarabin PY, Plu-Bureau G.
J Clin Endocrinol Metab 2011;Feb 2:[Epub ahead of print].
Study Question: Do progestogen-only contraceptives (POCs) increase the risk for myocardial infarction (MI)?
Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women—2011 Update: A Guideline From the American Heart Association
Mosca L, Benjamin EJ, Berra K, et al.
Circulation 2011;Feb 16:[Epub ahead of print].
Perspective: The following are 10 points to remember from the American Heart Association guidelines on the prevention of cardiovascular disease in women.

Efficacy and Safety of Glycoprotein IIb/IIIa Inhibitors During Elective Coronary Revascularization: A Meta-Analysis of Randomized Trials Performed in the Era of Stents and Thienopyridines
Winchester DE, Wen X, Brearley WD, Park KE, Anderson RD, Bavry AA.
J Am Coll Cardiol 2011;57:1190-1199.
Study Question: What is the efficacy and safety of glycoprotein IIb/IIIa inhibitors (GPIs) during elective percutaneous coronary intervention (PCI) in the contemporary era?

Total Arch Replacement Combined With Stented Elephant Trunk Implantation: A New “Standard” Therapy for Type A Dissection Involving Repair of the Aortic Arch?
Involving Repair of the Aortic Arch?
Sun L, Qi R, Zhu J, et al.
Circulation 2011;123:971-978.
Study Question: What is the appropriate approach for patients with type A dissection involving the aortic arch?

Effect of Cardiac Rehabilitation Referral Strategies on Utilization Rates: A Prospective, Controlled Study
Grace SL, Russell KL, Reid RD, et al., on behalf of the Cardiac Rehabilitation Care Continuity Through Automatic Referral Evaluation (CRCARE) Investigators.
Arch Intern Med 2011;171:235-241.
Study Question: What is the optimal strategy to maximize cardiac rehabilitation’s (CR) referral, enrollment, and participation?

Effectiveness of a Barber-Based Intervention for Improving Hypertension Control in Black Men. The BARBER-1 Study: A Cluster Randomized Trial
Victor RG, Ravenell JE, Freeman A, et al.
Arch Intern Med 2011;171:342-350.
Study Question: How effective are barbershop-based hypertension (HTN) outreach programs for black men in improving HTN control?

[Chevychelov]

Update on Venous Thromboembolism: Risk Factors, Mechanisms, and Treatments
Arteriosclerosis, Thrombosis, and Vascular Biology
Journal of the American Heart Association
Deep vein thrombosis (DVT) and pulmonary embolism, collectively called venous thromboembolism (VTE), are a public health crisis. The number of incident and recurrent VTE events are estimated at more than 1 million per year. Beyond the initial risk of death, estimated at greater than 30% within 30 days of the event, one third to one half of surviving patients develop recurrent thrombosis or long–term morbidity associated with post–thrombotic syndrome.
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

Direct association between dietary cholesterol intake and blood pressure: too good to be 'entirely' true
Journal of Hypertension
Official Journal of the International Society of Hypertension and the European Society of Hypertension
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A Novel Design of Posterior Leaflet Butterfly Resection for Mitral Valve Repair
Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery
Official Journal of the International Society for Minimally Invasive Cardiothoracic Surgery
[Ссылки доступны только зарегистрированным пользователям ]

Mechanisms and consequences of salt sensitivity and dietary salt intake
Current Opinion in Nephrology & Hypertension
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Cardiovascular Imaging for Assessing Cardiovascular Risk in Asymptomatic Men Versus Women: The Multi-Ethnic Study of Atherosclerosis (MESA)
Circulation: Cardiovascular Imaging
Journal of the American Heart Association
[Ссылки доступны только зарегистрированным пользователям ]

Progress in Prevention: Motivating Our Patients to Adopt & maintain Healthy Lifestyles
Journal of Cardiovascular Nursing
Official Journal of the Preventive Cardiovascular Nurses Association and Australasian Cardiovascular Nursing College
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[Chevychelov]

From the American College of Cardiology... Cilostazol Reduces Repeat Revascularizations for Long Lesions
Mar 7 - In patients implanted with long zotarolimus eluting stents, triple antiplatelet therapy including cilostazol safely reduces 8 month late loss and restenosis...
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From JACC... 'Valve-in-Valve' Technique Effective in Treating CoreValve Leaks
Mar 7 - Implanting a second CoreValve device inside a first one is an effective means of treating paraprosthetic leakage in patients undergoing transcatheter...
[Ссылки доступны только зарегистрированным пользователям ]

From Circulation: Cardiovascular Interventions... 'Mother-Child' Technique Improves Success for PCI in Challenging Lesions
Mar 4 - Inserting a 4 Fr catheter into a 6 Fr guiding catheter—the so called mother child technique—greatly improves the success rate for treating lesions...
[Ссылки доступны только зарегистрированным пользователям ]

From the American Journal of Cardiology... Meta-analysis: Multivessel PCI Comparable to Culprit-Only Approach in STEMI
Mar 4 - A strategy of multivessel percutaneous coronary intervention (PCI) performed at the time of culprit revascularization or during the same hospital stay...
[Ссылки доступны только зарегистрированным пользователям ]

From the American Journal of Cardiology... Early Bolus of Sodium Bicarb Reduces Contrast Nephropathy in Emergent PCI
Mar 3 - A rapid bolus injection of sodium bicarbonate immediately before contrast use drastically reduces the rate of contrast induced nephropathy (CIN) compared...
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From JACC... Autopsy Study: About One-Third of DES Contain New Atherosclerosis
Mar 2 - Neoatherosclerosis frequently develops in drug eluting stents (DES) within 2 years after implantation, according to a pathology study published online...
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From the Archives of Internal Medicine... Mental Outlook Linked to Long-term Survival After CHD Hospitalization
Mar 2- Patients hospitalized for coronary heart disease (CHD) who express high expectations for recovery later see their positive outlook come to fruition...
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From Circulation: Cardiovascular Quality and Outcomes... Many Cardiovascular Devices Approved by FDA Without Sex-Specific Data
Mar 1 - Most applications for high risk cardiovascular devices such as heart valves and stents that are eventually approved by the US Food and Drug Administration...
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[Chevychelov]

CVD medication usage of older patients heavily influenced by adverse effects
Fried T. Arch Intern Med. 2011;doi:10.1001/archinternmed.2011.32.

Researchers of a new study have found that the willingness of older patients to take medication for primary CVD prevention was highly sensitive to the medication's potential adverse events and relatively insensitive to its benefits.

“The findings in this study regarding variability in willingness to take medication according to its benefit are consistent with the results of earlier investigations,” the researchers wrote. “This study further demonstrated that changing the absolute benefit provided by the medication affected the willingness only of a small proportion of people unless the change in absolute benefit was substantial.”

The study involved 356 community-dwelling older participants (mean age, 76 years) who were questioned in a face-to-face interview about their willingness to medication to prevent MI. All volunteers were included in the study without exclusion.

According to study data, most participants (88%) were willing to take a medication that provided a 30% relative reduction in MI risk (six fewer people with MI out of 100) if there were no adverse events, with the percentage of willing patients increasing as the absolute benefit of the medication increased. The reasons those in the initial scenario turned down medications included the belief that the benefit was too small (n=13), belief that medication would have adverse effects (n=13) and an overall dislike of medications (n=7).

Of those who would take medication, 82% remained willing if the absolute benefit was decreased to three fewer people with MI. Conversely, medications with average benefit but that caused mild fatigue, fuzzy thinking and nausea would be turned down by 48% to 69% of the study population, whereas only 3% would take medications with severe enough effects to affect functioning.

These results, the researchers concluded, “suggest that clinical guidelines and decisions about prescribing these medications to older persons need to place emphasis on both their benefits and harms.”
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Recovery expectations for patients with CAD reflect long-term survival
Barefoot J. Arch Intern Med. 2011;doi:10.1001/archinternmed.2011.41.

The baseline recovery expectations of patients with coronary artery disease were shown to positively correlate with long-term survival and functioning in a new study.

Researchers from Duke University Medical Center and Duke Clinical Research Institute, Durham, N.C., enrolled patients (n=2,818) who underwent diagnostic coronary angiography at the medical center from 1992 to 1996. All patients were found to have clinically significant CAD (>75% diameter stenosis of >1 coronary artery).

At the 15-year follow-up, 1,637 deaths were reported, 885 of which were from CV causes. CABG was performed at some point during this period on 1,277 participants (45.3%), and percutaneous transluminal coronary angioplasty was performed on 1,156 participants (41%), whereas those who were not treated with one or both procedures received medical treatment (n=781; 27.7%).

Overall, expectations were positively associated with survival regarding total mortality (HR=0.76; 95% CI, 0.71-0.82) and CV mortality (HR=0.76; 95% CI, 0.69-0.83). After further adjustments for demographic and psychosocial covariates, the relationships remained but to a lesser extent for both total mortality (HR= 0.83; 95% CI, 0.76-0.91) and CV mortality (HR=0.79; 95% CI, 0.70-0.89). Similar associations (P<.001) were also found regarding functional status.

As potential mechanisms for explaining the observed benefits, the researchers said the predisposition of optimists makes their coping more effective in reducing risk factor levels and improving levels of life satisfaction, whereas pessimists tend to experience more tension and negative emotions during recovery, thereby heightening stress reactions.

These study’s findings, they wrote, “argue for expanded efforts to understand the influence of recovery expectations and the potential benefits of attempts to modify them. The potential feasibility of altering specific aspects of patient beliefs provides a promising avenue for intervention if the importance of expectations is confirmed.”

[Chevychelov]

FDA: Long-term proton pump inhibitor use linked with hypomagnesemia

The FDA has issued a public safety communication warning that the long-term use of prescription proton pump inhibitors is potentially associated with low magnesium levels.

Citing a review of 38 cases from the Adverse Event Reporting System and 23 cases from medical literature, the agency determined there was an association between hypomagnesemia-related adverse events in adult patients who had been taking proton pump inhibitors (PPIs) for at least 3 months. Most of the events occurred after 1 year of taking PPIs, and approximately one quarter of the cases required the discontinuation of PPI treatment (as well as magnesium supplementation). The agency also noted that since hypomagnesemia is likely under-reported and under-recognized, available data was insufficient to quantify an incidence rate.

Among the clinically serious events reported in the review were tetany, seizures, tremors, carpo-pedal spasm, atrial fibrillation, supraventricular tachycardia and abnormal QT interval.

The FDA communication said that the mechanism responsible for the association was not known, and recommended that patients on PPIs exhibiting symptoms of hypomagnesemia first talk to their health care providers before discontinuing any prescription PPI regimens.

“Health care professionals should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics or drugs that may cause hypomagnesemia,” the agency wrote in the announcement. “For patients taking digoxin, this is especially important because low magnesium levels increase the likelihood of serious side effects.”
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Antihypertensive treatment improved outcomes in non-hypertensive patients with CVD

Thompson A. JAMA. 2011;305:913-922.
Ventura H. JAMA. 2011;305:940-941.

Rates of all-cause mortality, stroke, congestive HF and composite CVD events were reduced in CVD patients without hypertension who were treated with antihypertensive medication, meta-analysis data suggested.

In the analysis, investigators searched databases for randomized controlled trials that analyzed the use of antihypertensive treatment for the prevention of CVD events in those with systolic BP of less than 140 mm Hg or diastolic BP of less than 90 mm Hg. The final group of studies included in the analysis (n=25) featured 64,162 patients without hypertension.

Researchers found that compared with controls, participants who received antihypertensive medications had pooled RR reductions in stroke (RR=0.77; 95% CI, 0.61-0.98), congestive HF (RR=0.71; 95% CI, 0.65-0.77), MI (RR=0.80; 95% CI, 0.69-0.93), CVD mortality (RR=0.83; 95% CI, 0.69-0.99), composite CVD events (RR=0.85; 95% CI, 0.80-0.90) and all-cause mortality from random-effects models (RR=0.87; 95% CI, 0.80-0.95). This translated to an absolute risk reduction per 1,000 people of –7.7 for stroke, -43.6 for chronic HF events, -13.3 for MI, -27.1 for composite CVD events, -15.4 for CVD mortality and -13.7 for all-cause mortality.

“Our results show that persons with a history of CVD but with BPs in the normal and prehypertensive ranges can obtain significant benefit from antihypertensive treatments,” the researchers wrote. “Additional randomized trial data are necessary to assess these outcomes in patients without CVD clinical recommendations.”

In an accompanying editorial, Hector O. Ventura, MD, with the John Ochsner Heart and Vascular Institute, New Orleans, and Carl J. Lavie, MD, with the University of Queensland School of Medicine, Brisbane, Australia, said this study adds to the understanding of treatment benefits with agents designed to lower BP among patients with CVD.

“The clinical importance of this study is clear: Pharmacological intervention in patients with CVD and BP levels less than 140/90 mm Hg is associated with a decreased risk of CV morbidity and mortality,” they said. “However, this study does not determine whether lowering BP levels is the reason for improved clinical outcomes. These agents may improve clinical outcomes through multiple other mechanisms (eg, hemodynamic effects unrelated to BP, neurohormonal effects and tissue-level effects).”
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Meta-analysis: Glycoprotein IIb/IIIa inhibitors linked with reduced nonfatal MI in elective PCI

Bhatt D. J Am Coll Cardiol. 2011;57:1200-1201.
Winchester D. J Am Coll Cardiol. 2011;57:1190-1199.

Results from a meta-analysis suggested that glycoprotein IIb/IIIa inhibitors are associated with reduced nonfatal MI and a nonsignificant increase in major bleeding in patients undergoing elective percutaneous coronary intervention.

Researchers identified 22 studies from a search of Medline, Cochrane and ClinicalTrials.gov databases that included patients undergoing elective PCI who were randomly assigned to glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors vs. controls. The 22 study populations yielded 10,123 patients. They then looked at 30-day outcomes and used a DerSimonian-Laird model to construct random effects summary RRs and CIs.

According to the results, the incidence of MI with GPIIb/IIIa inhibitors was 5.1% vs. 8.3% with controls (RR=0.66; 95% CI, 0.55-0.79) across the studies, and the results were no different when the analysis was restricted to placebo-controlled trials. The incidence of major bleeding was 1.2% with GPIIb/IIIa inhibitors vs. 0.9% with controls (RR=1.37; 95% CI, 0.83-2.25), and this failed to attain statistical significance. The difference in minor bleeding was more significant, however (3% with GPIIb/IIIa inhibitors vs. 1.7% with controls; RR=1.70; 95% CI, 1.28-2.26). All-cause mortality within 30 days did not differ between the two populations (0.3% with GPIIb/IIIa inhibitors vs. 0.5% with controls; RR=0.70; 95% CI, 0.36-1.33).

“In the current era of elective PCI performed with stents and thienopyridines, [GPIIb/IIIa inhibitors] reduced nonfatal MI without a notable increase in major bleeding,” the researchers concluded. “However, these agents increase minor bleeding and thrombocytopenia. Overall, the use of [GPIIb/IIIa inhibitors] during elective modern PCI seems to be safe and effective.”

In an accompanying editorial, Deepak L. Bhatt, MD, of the VA Boston Healthcare System and Brigham and Women’s Hospital, said the necessity of the routine use of GPIIb/IIIa inhibitors has been challenged in the context of stenting with adenosine diphosphate receptor antagonists, but the potential role of GPIIb/IIIa inhibitors in patients undergoing non-urgent PCI was far from outdated.

“This meta-analysis demonstrates that even on a background of aspirin, standard thienopyridine regimens and heparin — the PCI cocktail most commonly used worldwide — [GPIIb/IIIa inhibitors] continue to have an important potential role,” Bhatt wrote. “Notably, this data set further validates the concept that additional platelet inhibition is warranted beyond that provided by aspirin and standard-dose thienopyridines. Whether this in fact will be [GPIIb/IIIa inhibitors] or one of the other novel antiplatelet regimens remains to be seen.”

[Chevychelov]

Mandatory Electrocardiographic Screening of Athletes to Reduce Their Risk for Sudden Death: Proven Fact or Wishful Thinking?
Steinvil A, Chundadze T, Zeltser D, et al.
J Am Coll Cardiol 2011;57:1291-1296.
Study Question: Does preparticipation screening of athletes with a strategy including resting and exercise electrocardiography (ECG) reduce their risk for sudden death?

Real-Time 3D Echo in Patient Selection for Cardiac Resynchronization Therapy
Kapetanakis S, Bhan A, Murgatroyd F, et al.
JACC Cardiovasc Imaging 2011;4:16-26.
Study Question: What is the utility of three-dimensional transthoracic echocardiography (3DE) for quantifying left ventricular (LV) mechanical dyssynchrony as a predictor of clinical and anatomical success of cardiac resynchronization therapy (CRT)?

Early Diagnosis of Acute Myocardial Infarction in the Elderly Using More Sensitive Cardiac Troponin Assays
Reiter M, Twerenbold R, Reichlin T, et al.
Eur Heart J 2011;Feb 28:[Epub ahead of print].
Study Question: What is the diagnostic accuracy of high-sensitivity troponin (cTn) assays in elderly patients with chest pain?

Antihypertensive Treatment and Secondary Prevention of Cardiovascular Disease Events Among Persons Without Hypertension: A Meta-Analysis
Thompson AM, Hu T, Eshelbrenner CL, Reynolds K, He J, Bazzano LA.
JAMA 2011;305:913-922.
Study Question: Does treatment with antihypertensive medications among patients with a history of cardiovascular disease (CVD), but not hypertension reduce the risk of death and future CVD events?
The Effect of Mediterranean Diet on Metabolic Syndrome and Its Components: A Meta-Analysis of 50 Studies and 534,906 Individuals
Kastorini CM, Milionis HJ, Esposito K, Giugliano D, Goudevenos JA, Panagiotakos DB.
J Am Coll Cardiol 2011;57:1299-1326.
Study Question: Does a Mediterranean diet affect components of the metabolic syndrome?

Diabetes Mellitus, Fasting Glucose, and Risk of Cause-Specific Death
The Emerging Risk Factors Collaboration.
N Engl J Med 2011;364:829-841.
Study Question: What are the associations of baseline diabetes and fasting blood glucose level with the risk of cause-specific death?

Exceptions to Outpatient Quality Measures for Coronary Artery Disease in Electronic Health Records
Kmetik KS, O’Toole MF, Bossley H, et al.
Ann Intern Med 2011;154:227-234.
Study Question: Are outpatient quality measures for coronary artery disease (CAD) accurate based on electronic health records?
Long-Term Effects of Intensive Glucose Lowering on Cardiovascular Outcomes
The ACCORD Study Group.
N Engl J Med 2011;364:818-828.
Study Question: What are the 5-year outcomes of intensive glucose lowering on mortality and key cardiovascular events?

Functional Variants of the HMGA1 Gene and Type 2 Diabetes Mellitus
Chiefari E, Tanyolac S, Paonessa F, et al.
JAMA 2011;305:903-912.
Study Question: Is variation in a gene (HMGA1) resulting in reduced insulin receptor (INSR) expression associated with type 2 diabetes mellitus (T2DM)?

Diuretic Strategies in Patients With Acute Decompensated Heart Failure
Felker GM, Lee KL, Bull DA, et al., on behalf of the NHLBI Heart Failure Clinical Research Network.
N Engl J Med 2011;364:797-805.
Study Question: How does intravenous furosemide given as a bolus every 12 hours compare with continuous infusion and at either a low dose (equivalent to the patient’s previous oral dose) or a high dose (2.5 times the previous oral dose) in acute decompensated heart failure (ADHF)?

Low-Dose Computed Tomography Coronary Angiography With Prospective Electrocardiogram Triggering: Feasibility in a Large Population
Buechel RR, Husmann L, Herzog BA, et al.
J Am Coll Cardiol 2011;57:332-336.
Study Question: What is the feasibility of prospective electrocardiogram (ECG) triggering for low-dose computed tomographic coronary angiography (CTCA)?

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EARLY ACS: Routine vs. delayed provisional use of eptifibatide may improve patient outcomes
Wang T. Circulation. 2011;123;722-730.

New data have shown that patients with non–ST-elevation acute coronary syndrome who used early eptifibatide besides clopidogrel before angiography had lower rates of 30-day mortality and MI compared with those who used eptifibatide on a delayed provisional basis.

Investigators of the Early Glycoprotein IIb/IIIa Inhibition in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome (EARLY-ACS) trial included 9,166 patients with non–ST-elevation ACS who underwent angiography, of which 7,068 patients received upstream clopidogrel (Plavix, Sanofi-Aventis).

At 96 hours after invasive strategy, 9.2% of patients who received early eptifibatide (Integrilin, Millennium/Schering) vs. 9.6% of patients treated with the delayed provisional strategy experienced the primary endpoint of death, MI, recurrent ischemia requiring urgent revascularization or thrombotic bailout, whereas at 30 days, the difference in the secondary endpoint in death or MI was slightly more pronounced in favor of early use (10.9% vs. 12.1%; adjusted HR=0.90).

Furthermore, a significant reduction in death or MI at 30 days was reported in patients receiving upstream clopidogrel who also received early eptifibatide vs. delayed provisional (adjusted OR=0.85, 95% CI 0.73-0.99), but not in patients without intended upstream clopidogrel use.

“These findings lend support to the concept of enhanced value for additive antiplatelet therapies,” the researchers concluded. “Future investigations are needed to identify those patients who may benefit from more intensive platelet inhibition without a significant excess in bleeding risk.”

EARLY ACS was funded by research grants from Schering-Plough and Merck Pharmaceuticals.
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CONNECT: Wireless remote monitoring ICDs, CRT-Ds significantly lowered length of hospital stay
Crossley G. J Am Coll Cardiol. 2011;57:1181-1189.

When compared with standard in-office care, patients treated with implantable cardioverter defibrillators or cardiac resynchronization therapy defibrillators that featured wireless remote monitoring with automatic clinician alerts had significantly reduced mean length of hospital stay and time to a clinical decision, new data suggested.

As a result of these findings, the researchers wrote, “Clinics employing wireless remote monitoring may expect fewer total clinic visits per year while not increasing the rate of ED visits or CV hospitalizations for their patients.”

The Clinical Evaluation of Remote Notification to Reduce Time to Clinical Decision (CONNECT) trial included 1,997 patients from 136 clinical sites enrolled between November 2006 and May 2008. Each patient underwent insertion of an ICD or cardiac resynchronization therapy defibrillator (CRT-D) and were randomly assigned to either the remote monitoring arm (n=1,014) that utilized the Medtronic CareLink Network or the in-office arm (n=983).

During a follow-up of 15 months, the median time from clinical event to clinical decision was substantially reduced in the remote monitoring arm compared with the in-office arm (4.6 days vs. 22 days; P<.001). Also reduced in the remote monitoring group was the mean length of stay per CV hospitalization visit (3.3 days vs. 4 days; P=.002). Due to the reduction in length of stay, the estimated mean cost of hospitalization was considerably lower in the remote arm ($8,114 vs. $9,822).

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One-minute CPR training video improved attempt rate, skill of nonprofessionals

Bobrow B. Circ Cardiovasc Qual Outcomes. 2011;4:220-226.

Individuals who were trained with a 60-second hands-only CPR training video had significantly higher rates of average compression and compression depth vs. a control group that did not view the video.

Investigators of the prospective study enrolled adults (n=336) who had not received previous CPR training and randomly assigned them into four training groups: no training (control; n=51); 60-second video training (n=95); 5-minute video training (n=99); and 8-minute video training that included mannequin practice (n=91). Participants had their CPR performance ability tested during an adult out-of-hospital cardiac arrest scenario using a CPR-sensing mannequin and computer software (Laerdal PC SkillReporting, Laerdal Medical).

After training, participants were randomly assigned to be tested either immediately or after a 2-month delay. Regardless of experimental group, researchers reported that, compared with control, video training had a significant effect on increasing average compression rate closer to the recommended 100/minute (P<.001 for all), as well as increasing the average compression depth (>38 mm; P<.0001 for all).

These findings, the researchers wrote, add to the current understanding of the effectiveness of CPR training, showing how adults without previous formal CPR training can learn, demonstrate and retain effective hands-only CPR skills with a single viewing of an ultra-brief, 60-second training video.

“Because of its brevity, the ultra-brief hands-only CPR video creates opportunities for frequent, recurrent training in multiple venues and the potential to increase the likelihood of lay citizens being recurrently and effectively trained in this technique,” they said. – by Brian Ellis

This article is very interesting. Out-of-hospital cardiac arrest at present has a miserable prognosis. In those reaching the hospital, only a very small number survive to leave the hospital without significant neurologic damage. Eventual return of spontaneous circulation is more likely if cardiac resuscitation is begun immediately, but as stated in the article, there are many barriers to the bystanders delivering effective CPR. Chief among them is the fear of performing mouth-to-mouth breathing.

There has for years been evidence from Gordon Ewy, MD, of University of Arizona, that cardiac compression was the effective activity in resuscitation (and that ventilation was less important). Now, the American Heart Association has adopted the change so that instead of ABC (airway, breathing, compression), the motto is now CAB. The study presented shows in an artificial, non-emergency setting that with extremely minimal training of hands-only resuscitation, the essential aspects of CPR can be learned. It also shows that for at least 2 months, the technique can be retained. Whether more people witnessing a real cardiac arrest will immediately perform CPR as a result is still an open question. If there is a significant increase in out-of-hospital resuscitations by this hands-only technique, the results will likely be similar to those with the old ABC technique as demonstrated by Svensson et al (N Engl J Med. 2010;363:434-442), but whether this will yield a better eventual prognosis for these patients has yet to be proved.
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Imaging modality may detect abnormal resting coronary blood flow

Chow B. J Am Coll Cardiol. 2011;57:1280–1288.

Rybicki F. J Am Coll Cardiol. 2011;57:1289-1290.

Changes in corrected coronary opacification within the coronary lumen detected by computed tomographic coronary angiography were predictive of abnormal resting coronary blood flow, suggested a new study.

The Canadian researchers conducted this proof-of-concept study by assessing 104 coronary arteries from 52 patients (mean age, 60 ± 9.5 years) via computed tomographic coronary angiography (CTA). All patients were without a history of revascularization, congenital heart disease and heart transplantation, and had obstructive CAD in at least one vessel and at least one major epicardial vessel for use as a “normal” reference artery.

According to data, differences in corrected coronary opacification (CCO) were greater in arteries with CTA diameter stenoses ≥ 50%, as were the CCO differences in arteries with thrombolysis in MI flow grade ≤3 (0.406 ± 0.226) vs. TIMI flow grade 3 (0.078 ± 0.078; P<.001). With regard to CCO differences, CTA detected abnormal coronary flow (TIMI flow grade <3) with a sensitivity of 83.3%, specificity of 91.2%, accuracy of 88.5%, positive predictive value of 83.3% and negative predictive value of 91.2%.

“The ability of CTA to estimate coronary blood flow and to assess for functional coronary stenosis would be extremely desirable,” the researchers wrote of their findings. “Such a technique might prove to be useful in settings of unevaluable coronary segments, perhaps by improving the diagnostic accuracy of CTA. Equally important would be its potential applicators to measure stress coronary blood flow, thus permitting the assessment of hemodynamic significance of a lesion.”

Frank J. Rybicki, MD, PhD, with the Brigham and Women’s Hospital and Harvard Medical School, Boston, commented in an accompanying editorial that “Coronary imaging will define the next generation of ‘state-of-the-art’ in CT, and future generations of hardware technology are likely to change the way we think about image acquisition. While we collectively study these gains and new applications, it is essential to recognize, optimize and study the properties of coronary artery enhancement to maximize our understanding of CT angiography and optimally use it for patient care.”

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ACTIVE I: Irbesartan failed to lower CV events in patients with AF
Yusuf S. N Engl J Med. 2011;364:928-938.

Among patients with atrial fibrillation, irbesartan, an angiotensin-receptor blocker, did not reduce the occurrence of CV events, including MI and death from vascular causes, compared with placebo, according to randomized, clinical trial data.

In the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE-I) trial, investigators enrolled patients (n=9,016; mean age, 69.6 years) who had permanent AF or at least two episodes of intermittent AF in the previous 6 months. Patients were then randomly assigned to receive either irbesartan (Avapro, Sanofi-Aventis/Bristol-Myers Squibb) or placebo. The first coprimary outcome was defined as MI, stroke or death from vascular causes, and the second was this composite outcome plus hospitalization for HF.

During a mean follow-up of 4.1 years, patients taking irbesartan had a mean reduction in systolic BP of 2.9 mm HG and diastolic BP of 1.9 mm Hg. There was no difference in the first coprimary endpoint between groups (5.4% each per 100 patient years), and only nonsignificant reduction in the second coprimary endpoint in the irbesartan group (7.3% vs. 7.7% per 100 patient years; P=.12).

When rates of hospitalization were looked at individually, researchers found that patients given irbesartan had a nominally significant reduction in first hospitalization for HF (HR=0.86; 95% CI, 0.76- 0.98), but not in the risk of hospitalization for AF (HR=0.95; 95% CI, 0.85-1.07).

“Among patients with AF, most of whom had well-controlled hypertension and 60% of whom were receiving an ACE inhibitor, the addition of irbesartan did not reduce the risk of death from CV causes, stroke or MI or this composite outcome plus hospitalization for HF,” the researchers wrote, later adding that it remains to be seen whether more aggressive lowering of BP would be effective in patients with AF.
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Mandatory ECG screening in Israel failed to lower sudden death, cardiac arrest risk

Bove A. J Am Coll Cardiol. 2011;57:1297-1298.
Steinvil A. J Am Coll Cardiol. 2011;57:1291-1296.

Twelve years after Israel enacted the National Sport Law, which mandates electrocardiographic screening and exercise stress testing of all athletes, the incidence of cardiac arrest or sudden death did not change compared with 12 years before the law went into effect.

The National Sport Law requires that a medical questionnaire, physical examination, baseline ECG and exercise stress testing be completed by all athletes. Data for the current study were compiled by researchers during a systematic search of two main Israeli newspapers, which provided the yearly number of cardiac arrests among competitive athletes, whereas the Israel Sport Authority provided the size of the population at risk.

Between 1985 and 2009, 24 documented sudden death or cardiac arrest events occurred to competitive athletes, with 11 events reported 12 years before and 13 events reported 12 years after legislation. This resulted in an average yearly incidence of 2.6 events per 100,000 athlete years. Specifically, before legislation, the mean yearly incidence was 2.54 events per 100,000 athlete years vs. 2.66 events per 100,000 athlete years after legislation (P=.88).

“Sudden death among athletes is a very rare phenomenon,” the researchers wrote. “When the prevalence (or pretest probability) is so low, it is inevitable that many people with abnormal test results (abnormal ECG results) will represent false positive results. Of note, disqualification from participation in sports because of abnormal ECG results obtained during an obligatory (often unsolicited) screening has profound implications for the asymptomatic athlete. Therefore, before mandatory ECG screening is endorsed universally, it is reasonable to request additional proof that such a strategy actually saves lives.”

In an accompanying editorial, Alfred A. Bove, MD, PhD, with the Temple University School of Medicine, Philadelphia, said disqualifying athletes based on false positive ECG findings is a concern, and he made a suggestion on how physicians can limit the occurrence.

“At present, cardiologists who evaluate athletes should be familiar with the normal variants in echocardiography and ECG results and should incorporate the 12 questions posed by the American Heart Association for screening so that young athletes are not disqualified based on variant ECG results or normal cardiac adaptations to exercise,” Bove said.
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AHA publishes transition guidelines for adolescent congenital heart disease patients
Sable C. Circulation. 2011;doi:10.1161/cir.0b013e3182107c56.

The American Heart Association has issued a scientific statement outlining best practices for the transition of young patients with congenital heart disease into adulthood, the first step of which is to begin the process in early adolescence, between the ages of 12 and 14 years.

“It’s not as simple as getting the name of a new doctor and going to see them when a patient turns 18,” Craig Sable, MD, AHA statement committee co-chair, said in a press release. “There are multiple steps associated with the transition process that need to be started at a very young age.”

The AHA’s statement was based on a review of transition literature conducted by Sable and his team, beginning in 2008.

To provide uninterrupted medical care, the AHA recommends that the transition should be a joint effort between the patient, the patient’s family and the health care provider, who is usually a pediatric heart specialist. Critical steps for the patient and his or her team to consider on behalf of the patient, according to the statement, are:
Selecting an adult care physician to provide coordinated comprehensive care.
Receiving reproductive, genetic and career counseling.
Obtaining health insurance.
Educating adult care providers on congenital heart disease management.
Maintaining communication between patients, families and health care professionals.

Less than one-third of adults with congenital heart disease receive specialist care, Sable said.

“The vast majority of the patients we see are not necessarily the most severe, so there’s a real concern that some of the patients who really need care are not seeking it. The bottom line is to ensure that, as patients grow up, they receive the necessary care,” he said.

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Early Detection and Prediction of Cardiotoxicity in Chemotherapy-Treated Patients
Sawaya H, Sebag IA, Plana JC, et al.
Am J Cardiol 2011;Mar 7:[Epub ahead of print].
Study Question: What is the predictive ability of more sensitive echocardiographic measurements and biomarkers on future cardiac dysfunction in chemotherapy-treated patients?

Effect of Obesity and Overweight on Left Ventricular Diastolic Function: A Community-Based Study in an Elderly Cohort
Russo C, Jin Z, Homma S, et al.
J Am Coll Cardiol 2011;57:1368-1374.
Study Question: What is the effect of increased body size on left ventricular (LV) diastolic dysfunction?

Pro–B-Type Natriuretic Peptide1-108 Circulates in the General Community: Plasma Determinants and Detection of Left Ventricular Dysfunction
Macheret F, Boerrigter G, McKie P, et al.
J Am Coll Cardiol 2011;57:1386-1395.
Study Question: What is the ability of circulating pro-B-type natriuretic peptide (proBNP1-108) to detect left ventricular (LV) dysfunction in the general population?

Irbesartan in Patients With Atrial Fibrillation
The ACTIVE I Investigators.
N Engl J Med 2011;364:928-938.
Study Question: What are the effects of irbesartan on the risk of cardiovascular events and maintenance of sinus rhythm in patients with atrial fibrillation?

Olmesartan for the Delay or Prevention of Microalbuminuria in Type 2 Diabetes
Haller H, Ito S, Izzo JL Jr, et al., on behalf of the ROADMAP Trial Investigators.
N Engl J Med 2011;364: 907-917.
Study Question: What is the effect of treatment with olmesartan on the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria?
Preventing Weight Gain by Lifestyle Intervention in a General Practice Setting: Three-Year Results of a Randomized Controlled Trial
Ter Bogt NC, Bemelmans WJ, Beltman FW, Broer J, Smit AJ, van der Meer K.
Arch Intern Med 2011;171:306-313.
Study Question: Can an intervention implemented in a general office practice prevent weight gain among adults?

Association Between Body-Mass Index and Risk of Death in More Than 1 Million Asians
Zheng W, McLerran DF, Rolland B, et al.
N Engl J Med 2011;364:719-729.
Study Question: Is body mass index (BMI) associated with increased mortality risk among Asian men and women?

Effect of Nitroglycerin Ointment on Bone Density and Strength in Postmenopausal Women: A Randomized Trial
Jamal SA, Hamilton CJ, Eastell R, Cummings SR.
JAMA 2011;305:800-807
Study Question: What is the effect of nitroglycerin on bone mineral density (BMD) in postmenopausal women?

Improving Safety in the Electrophysiology Laboratory Using a Simple Radiation Dose Reduction Strategy: A Study of 1007 Radiofrequency Ablation Procedures
Rogers DP, England F, Lozhkin K, Lowe MD, Lambiase PD, Chow AW.
Heart 2011;97:366-370.
Study Question: How effectively do radiation dose-reduction maneuvers (RDRMs) decrease radiation exposure in the electrophysiology laboratory?

Effectiveness of Cardiac Resynchronization Therapy by QRS Morphology in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT)
Zareba W, Klein H, Cygankiewicz I, et al.
Circulation 2011;123:1061-1072.
Study Question: Is the response to cardiac resynchronization therapy (CRT) affected by QRS morphology in patients enrolled in the MADIT-CRT trial?

Permanent Pacemaker Insertion After CoreValve Transcatheter Aortic Valve Implantation: Incidence and Contributing Factors (the UK CoreValve Collaborative)
Khawaja MZ, Rajani R, Cook A, et al.
Circulation 2011;123:951-960.
Study Question: What are the incidence and determinants of permanent pacemaker (PPM) need in patients undergoing transcatheter aortic valve implantation (TAVI) using CoreValve?

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Progress in hypertrophic cardiomyopathy has saved lives, but knowledge gaps exist

As the main cause of sudden cardiac death in the developed world for people younger than 35 years, it is perhaps not surprising that hypertrophic cardiomyopathy is most often regarded as a disease that strikes without warning and leaves family members and friends reeling from the loss of a loved one.

However, although unpredictable sudden death is a characteristic of hypertrophic cardiomyopathy (HCM), it does not represent the overall outlook for patients with this disease today, more than 50 years since it was first recognized in a patient.

Barry J. Maron, MD, said despite the complexity and unpredictability of HCM, substantial progress has been made in the diagnosis and treatment of the disease.

“After 50 years, we have arrived at a different place, where this is a treatable disease, compatible with a normal life expectancy, and sometimes without the necessity of treatment because probably the vast majority of affected people live their lives without any major complications from HCM and may not even know they have it,” Barry J. Maron, MD, director, Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, told Cardiology Today.

Still, Maron said more must be done to increase the awareness of this disease.

“Time to time, there have been misunderstandings about what [HCM] is and how it’s treated and what patients can expect from a diagnosis,” he said. “So that continues to be an obstacle for the patient population because HCM is relatively uncommon in CV practice, making it easy to understand why rapid developments in this disease may not immediately penetrate the knowledge of everyone practicing cardiology.”

Locating the source of the disease

Despite its first modern description in a patient in 1957, the cause of HCM remained much a mystery for more than 3 decades until Seidman and colleagues began to unravel the genetic foundation of the disease. Their findings showed a mutation in the MYH7 gene in a family with HCM. After this discovery, more than a dozen genes were also implicated in HCM, with MYH7 and MYBPC3 now regarded as the most common causal genes, accounting for approximately 50% of all HCM cases.

Currently, the gene for HCM occurs in at least one of every 500 people. The disease, with complications ranging from angina and dyspnea to arrhythmia, is clinically diagnosed based on the detection of cardiac hypertrophy via an echocardiogram. This detection method, however, is not without shortcomings, as the likelihood of patients with a clinical diagnosis of HCM being misdiagnosed because of phenocopy conditions may be as high as 10%, said A. J. Marian, MD, professor and director, Center for Cardiovascular Genetics with The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston.

“There are conditions, such as storage diseases, that can cause cardiac hypertrophy. Clinically, they may be similar to true HCM, but they have different mechanisms involved,” Marian said, adding that the consequence of mistaking the disease is that the patient will be given the wrong treatment.

Although this discrepancy opens the door for more precise genetic testing, this method too has its share of challenges to overcome, said James B. Young, MD, professor of medicine of the Cleveland Clinic Foundation and Cardiology Today Section Editor.

“Physicians are often unclear on how to use molecular diagnostic tools, when to order genetic and genomic testing, and when to search for various mutations. There is just a lot of confusion out there regarding this strategy,” Young said in an interview, further noting that HCM “often isn’t at the top of somebody’s differential diagnosis. A patient comes in with atypical symptoms, chest discomfort, particularly in a young individual, and [physicians] may not list this high in their differential diagnosis because perhaps we haven’t educated folks enough about the frequency of the problem and the importance of the problem.”

During the past decade, patients with HCM at high risk for sudden death have benefited from the use of implantable cardioverter defibrillators. One study that tested the device in a high-risk population was conducted by Maron and colleagues and published in a 2007 issue of the Journal of the American Medical Association. According to their results, ICD interventions in 506 patients up to a 17-year interval terminated ventricular fibrillation and ventricular tachycardia in 20% of the study population, with only one sudden cardiac death, which was attributed to an ICD malfunction.

“The importance of the study is that it shows that sudden death [associated with HCM] is preventable, and that the ICD is the only treatment for HCM known to prolong life,” Maron said.

ICD therapy, as well as surgical myectomy surgery, transplantation and alcohol ablation for HF, represent dramatic hits regarding how to approach patients with the disease, but the role of drug treatment in HCM still remains uncertain.

“One persistent problem is how do you treat these patients with medications? We have not had a good clinical trial that has given us insight,” said Robert Roberts, MD, president and CEO of the University of Ottawa Heart Institute and Cardiology Today Editorial Board member. “There are several drugs people use, like beta-blockers, calcium-channel blockers and disopyramide (Norpace, Pfizer), but those are directed more toward the symptomatic patient population rather than patients with HCM having hypertrophy without symptoms.”

Currently, Marion said, pharmaceutical treatment in HCM is empiric. “In adults, no treatment has been shown to reverse or prevent the evolution of cardiac hypertrophy or fibrosis in HCM,” he said. “However, prevention of cardiac hypertrophy and fibrosis through pharmacological interventions could possibly reduce the risk of sudden cardiac death and perhaps even eliminate it.”

In addition, Roberts said there have been several animal models that have explained numerous findings of HCM, which may have future consequence in the treatment of this disease. These include studies that have shown use of a statin drug, an ACE inhibitor, an aldosterone inhibitor and N-acetylcysteine in mice and rabbits given the human HCM gene to be able to significantly ameliorate the disease.

“Unfortunately, we have never been able to get funding to do the trial in humans,” Roberts said. “Despite it being a common cause of sudden death, it is still a rare disease. In order to do a clinical trial, you would have to find a large number of centers. But, so far, drug companies have not been keen on doing such a study, in part because they are looking at a small population.”

The role of molecular biology in the treatment of HCM for Maron, however, remains unclear and unlikely to be the ultimate answer. “The whole idea of some sort of molecular ‘cure’ ignores one important point: This is a very powerful and heterogeneous genetic heart disease that will be very difficult to reverse in its entirety. It’s unlikely that it will ever be reversible by molecular biology,” he said.

Nevertheless, obtaining funding for research into HCM to try to answer these questions remains paramount.

“There has been very little if any funding available from NIH for clinical research related to genetic diseases, such as HCM,” Maron said. “In my view, it is unfair that our major granting institutions do not put much weight in these less common diseases. For people with HCM, it’s the most common disease in the world.”

“This is a disease in which we know an awful lot and we’re ready to do clinical trials,” Roberts said. “Given the devastating nature of the disease, it would be most unfortunate if we cannot find funding to do that.”

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Screening tool improved appropriate referrals for ICD implant
Gravelin L. Circ Cardiovasc Qual Outcomes. 2011;4:152-156.

The use of a screening tool increased the likelihood of referral to an electrophysiologist among patients in whom an implantable cardioverter defibrillator would help prevent sudden cardiac death, a new study suggested.

Laura M. Gravelin, MD, and investigators examined screening tools from medical records of patients from two outpatient cardiology offices. The screening tool analyzed in this study questioned general cardiologists as to whether their patients’ ejection fraction was 35% or less, and if so, the physician was then asked whether the patients were referred to an electrophysiologist for an ICD. Appropriate referrals in the screening group were then compared with similar data before screening tool implementation.

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Researchers reported that significantly more eligible patients were offered a referral during the screening period vs. pre-implementation at both sites. Specifically, at site one, the referral rate was 80% (eight of 10 eligible patients) vs. 33% (five of 15; P<.02 for trend) in favor of the screening period, whereas at site two, it was 100% (44 of 44 eligible patients) vs. 60% (21 of 35; P<.001 for trend) in favor of screening. Among all patients referred, 41% accepted. No sex-specific differences were reported in this study.

Besides these findings, researchers said barriers to referral include physicians’ understanding and recollecting the importance of ICD therapy for primary prevention, as well as patients’ willingness to undergo evaluation.

“Verification of these findings on a larger scale, as well as studies defining the foundation of these barriers, may further improve use of ICDs in patients for whom their mortality benefit is well described,” they said. – by Brian Ellis



The study by Gravelin et al illustrates the potential for integrating guidelines into daily clinical practice, ideally through use of an electronic medical record, which can alert clinicians to the potential for life-saving treatments such as an ICD. Guidelines are not recipes or mandates for care, but are rather useful "check lists" of factors to be considered. Alerting clinicians to factors such as a low ejection fraction is similar to highlighting abnormal lab values such as a high potassium or low blood sugar.

Whether or not to implant an ICD is a complex decision, however, and one that should be made by an expert clinician who considers more than just the ejection fraction, which is only the beginning of the story. An opportunity exists to glean additional information from the medical record that would complement and improve on a simple ejection fraction measurement to select patients who would benefit from an ICD, to uncover new, real-time, real-world data that could be used to improve the guidelines.

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Researchers examine CV risks related to chronic kidney disease treatments
Kestenbaum B. JAMA. 2011;305:1138-1139.
Palmer S. JAMA. 2011;305:1119-1127.

In a recent study, researchers were unable to find a correlation between serum levels of calcium and parathyroid hormone and the risk for CV mortality or all-cause death in patients with chronic kidney disease, although higher serum phosphorus in this population was linked with increased mortality risk.

This systematic review and meta-analysis included 47 cohort studies with a total of 327,644 patients. All studies measured the association between death and CV events and serum levels of phosphorus, parathyroid hormone or calcium, which are recommended in clinical practice guidelines for the management of mineral and bone disorders related to chronic kidney disease (CKD).

According to data, the risk for all-cause mortality increased with each 1-mg/dL increase in serum phosphorus (RR=1.18), but the likelihood of death remained largely unchanged with increased serum levels of parathyroid hormone (per 100-pg/mL increase, RR=1.01) and calcium (per 1-mg/dL increase, RR=1.08). Similarly, rates of CV mortality were only slightly affected with increased levels of serum phosphorus (RR=1.10), parathyroid hormone (RR=1.05) or calcium (RR=1.15).

These data, the researchers wrote, do not support the hypothesis that individuals with CKD should have treatment to achieve targeted levels of serum parathyroid hormone or calcium to reduce mortality or CV morbidity, “except at extreme levels in which hypocalcemia and hypercalcemia result in immediate, clinically apparent adverse events such as tetany and seizures,” they said. “Furthermore, treating high phosphorus levels is linked to a substantial pill burden that is associated with lower quality of life in individuals with CKD. While we do not conclude that normalizing serum levels of calcium or phosphorus or avoiding upper or lower extremes of serum level of parathyroid hormone is futile, high-quality evidence is required before specific treatment should be advocated strongly.”

However, extrapolating this research into clinical guidelines currently, wrote Bryan Kestenbaum, MD, with the University of Washington, Seattle, in an accompanying editorial, remains premature.

“Placebo-controlled clinical trials are the necessary next step to determine the risks and benefits of treatments that target mineral metabolism disturbances in patients with CKD as a means to improve their health,” he said.