Обзор американских кардиологических журналов за неделю (ссылки)

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Trial Summary
DANPACE Title: Danish Multicenter Randomised Trial on Single-Lead Atrial Versus Dual-Chamber Pacing in Sick Sinus Syndrome
Trial Sponsor: Medtronic, St. Jude Medical, Boston Scientific, Ela Medical, Pfizer, and the Danish Heart Foundation
Year Presented: 2010
Topic(s): Arrhythmias, Prevention/Vascular, General Cardiology
Summary Posted: 08/31/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: NOTHING TO DISCLOSE
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Reviewer Disclosure: RESEARCH/RESEARCH GRANTS: Astra Zeneca, Heartscape, Eisai, Sanofi Aventis, The Medicines Company, Ethicon, Bristol Myers Squibb Cogentus, PLx Pharma, Takeda

Description:

The goal of the trial was to evaluate treatment with single-lead atrial pacing compared with dual-chamber pacing among patients with sick sinus syndrome.
Hypothesis:

Dual-chamber pacing will be more effective in preventing pacemaker-related complications.
Drugs/Procedures Used:
Patients with sick sinus syndrome were randomized to single-lead atrial (AAIR) pacing (n = 707) versus dual-chamber (DDDR) pacing with an atrioventricular (AV) interval of ≤220 msec (n = 708).

Lower rate was set at 60 bpm and upper rate was set at 130 bpm. For DDDR, paced AV interval was ≤220 msec and sensed AV interval was ≤200 msec.
Concomitant Medications:

At randomization, in the AAIR group, the use of anticoagulation was 15%, aspirin 52%, class I antiarrhythmic 2%, amiodarone 4%, sotalol 6%, and beta-blocker 23%.
Principal Findings:
Overall, 1,415 patients were randomized. In the AAIR group, the mean age was 74 years, 67% were women, 10% had diabetes, and left ventricular dysfunction was present in 11%.

Pacing in the atrium was 58% in the AAIR group and 59% in the DDDR group. Pacing in the ventricle was 65% in the DDDR group.

At a mean follow-up of 5.4 years, survival was similar between the groups (p = 0.53), atrial fibrillation was increased with single-lead atrial pacing (p = 0.024), and need for reoperation was increased with single-lead atrial pacing (p < 0.001). Also, stroke was similar (p = 0.56) as well as hospitalization for heart failure (p = 0.90).
Interpretation:

Among patients with sick sinus syndrome, dual-chamber pacing appears to be superior to single-lead atrial pacing. Dual-chamber pacing resulted in reduced frequency of atrial fibrillation and need for reoperation. Survival and stroke were similar between the groups. These findings contradict some other studies. Current guidelines recommend that patients with sinus node dysfunction without AV conduction abnormality may be treated with a single-chamber atrial pacemaker.
Conditions:
Pacing
Arrhythmias
Prevention
Therapies:
Pacing
Pacing / DDD(R)
Pacing / Dual chamber
Pacing / AAI
Study Design:
Parallel. Randomized.
Primary Endpoints:
All-cause mortality
Secondary Endpoints:
Paroxysmal atrial fibrillation
Chronic atrial fibrillation
Stroke
Heart failure
Pacemaker reoperation
Patient Population:
Symptomatic bradycardia and sinus pause >2 seconds or sinus bradycardia <40 bpm while awake
PR interval ≤0.22 second (age 18-70 years) or PR interval ≤0.26 second (age >70 years)
QRS width ≤0.12 second

Number of enrollees: 1,415
Duration of follow-up: mean 5.4 years
Mean patient age: 74 years
Percentage female: 67%
New York Heart Association class: I: 71%, II: 24%, III: 4%, IV: 0%
Exclusions:
AV block
Bundle branch block
Persistent atrial fibrillation
Atrial fibrillation with QRS rate <40 bpm for ≥1 minute or >3-second pause
Carotid sinus hypersensitivity
References:

Presented by Dr. Jens Nielsen at the European Society of Cardiology Congress, Stockholm, Sweden, August 2010

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Trial Summary
ANTIPAF Title: Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation
Trial Sponsor: German Ministry of Research and Education, Daiichi Sankyo
Year Presented: 2010
Topic(s): Arrhythmias, Prevention/Vascular
Summary Posted: 08/31/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: NOTHING TO DISCLOSE
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Reviewer Disclosure: RESEARCH/RESEARCH GRANTS: Astra Zeneca, Heartscape, Eisai, Sanofi Aventis, The Medicines Company, Ethicon, Bristol Myers Squibb Cogentus, PLx Pharma, Takeda

Description:

The goal of the trial was to evaluate treatment with olmesartan compared with placebo among patients with paroxysmal atrial fibrillation (AF).
Hypothesis:

Olmesartan will be more effective in reducing AF burden.
Drugs/Procedures Used:

Patients with paroxysmal AF were randomized to olmesartan (n = 214) versus placebo (n = 211), stratified by concomitant beta-blocker use.
Concomitant Medications:

At baseline, in the olmesartan group, the use of dihydropyridine calcium channel blocker was 14%, diltiazem was 0.5%, verapamil was 2%, other calcium channel blocker was 17%, class IV antiarrhythmic was 3%, statin was 15%, and aspirin was 29%.
Principal Findings:
Overall, 425 patients were randomized. In the olmesartan group, the mean age was 61 years, 38% were women, 9% were diabetic, mean systolic blood pressure was 132 mm Hg, mean left ventricular ejection fraction was 63%, and 37% had a mean left atrial diameter >40 mm.

The primary outcome, AF burden, was similar between the groups (p = 0.77). Cumulative incidence of AF recurrence was similar between the groups (p = 0.69), and cumulative incidence of persistent AF was also similar between the groups (p = 0.81).

Any serious adverse event occurred in 4.7% of the olmesartan group versus 5.2% of the placebo group (p = 0.80).
Interpretation:

Among patients with paroxysmal AF, olmesartan was not effective at reducing AF burden or the incidence of recurrent or persistent AF. While there is evidence that angiotensin-receptor blockers may be useful for primary prevention of AF, these agents do not appear to be useful for secondary prevention. Other strategies are needed in this patient population.
Conditions:
Arrhythmias / Atrial fibrillation
Prevention/Primary
Arrhythmias
Therapies:
Beta blocker
Angiotensin-receptor blocker
Medical
Study Design:
Placebo Controlled. Randomized. Parallel. Stratified.
Primary Endpoints:

Percentage of days in AF in 1 year
Patient Population:
Paroxysmal AF within the last 6 months
At least 18 years of age

Number of enrollees: 425
Mean patient age: 61 years
Percentage female: 38%
Exclusions:
Use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers
Class I or III antiarrhythmic medications
Beta-blocker therapy after randomization
References:

Presented by Dr. Andreas Goette at the European Society of Cardiology Congress, Stockholm, Sweden, August 2010.

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New P2Y12 inhibitors decreased mortality, major adverse cardiac events after PCI vs. clopidogrel
Bellemain-Appaix A. J Am Coll Cardiol. 2010;doi:10.1016/j.jacc.2010.07.012.

New P2Y12 inhibitors, including prasugrel, ticagrelor, cangrelor and elinogrel, when compared with clopidogrel decreased death and major adverse cardiac events after percutaneous coronary intervention, according to data from a new study featured in the Journal of the American College of Cardiology.

Researchers utilized Medline and Cochrane databases to search for randomized, placebo-controlled trials comparing new P2Y12 antagonists with clopidogrel (Plavix, Sanofi-Aventis) in PCI between 1980 and 2010. The final analysis included eight studies (n=48,599) in which 94% of patients had acute coronary syndrome and 84% of patients underwent PCI.

Of the study population, 50.8% (n=24,697) of patients received a new P2Y12 inhibitor. New inhibitors vs. clopidogrel decreased death (2.75% vs. 3.35%; OR=0.83; 95% CI, 0.75-0.92), CV death (2.95% vs. 3.61%; OR=0.82; 95% CI, 0.72-0.92), and major adverse coronary events (8.81% vs. 10.33%; OR=0.86; 95% CI, 0.8-0.93). MI, stent thrombosis and target vessel revascularization were all also significantly decreased; however there was an increase in thrombolysis in MI major bleeding (1.78% vs. 1.43%; OR=1.21; 95% CI, 1.05-1.4).

“The main finding of the present meta-analysis is the decrease in mortality observed with these new P2Y12 inhibitors compared with clopidogrel when used in patients treated with PCI,” researchers concluded. “The net benefit is particularly marked in PCI for STEMI patients, in which there is no significant increase in major bleeding when compared with clopidogrel.”
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Retroperitoneal hematoma found an uncommon complication of PCI
Trimarchi S. J Am Coll Cardiol Intv. 2010;3:845–850.

Retroperitoneal hematoma was not a common complication of contemporary percutaneous coronary intervention, although it was associated with high morbidity and mortality in a study examining patients from a large, multicenter registry.

Researchers analyzed 112,340 patients from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium registry who were undergoing PCI between October 2002 and December 2007. The evaluated endpoints included the development of retroperitoneal hematoma and mortality.

Of the 482 (0.4%) patients with retroperitoneal hematoma, 92.3% were treated medically and 7.7% underwent surgical repair. Independent predictors of retroperitoneal hematoma included: female sex, body surface area of less than 1.8 m², emergency procedure, history of chronic obstructive pulmonary disease, cardiogenic shock, pre-procedural IV heparin, pre-procedural glycoprotein IIb/IIIa inhibitors, adoption of sheath size of at least 8-French, and use of vascular closure devices.

Furthermore, researchers noted that retroperitoneal hematoma development correlated with a higher frequency of post-procedure MI (5.81% vs. 1.67%), infection and/or sepsis (17.43% vs. 3%), HF (8% vs. 1.63%) and in-hospital mortality (6.64% vs. 1.07%; P<.0001 for all) vs. those who did not develop retroperitoneal hematoma.

These findings, the researchers wrote, “[agree] with previous literature suggesting that [retroperitoneal hematoma] is an uncommon complication in patients undergoing PCI … and confirm the association between the development of [retroperitoneal hematoma] and a significantly higher risk of morbidity and mortality. Although it remains to be determined, the identification of risk factors for the development of [retroperitoneal hematoma] could lead to modification of procedure strategies aimed toward reducing its incidence, such as the adoption of a radial artery approach in high-risk patients.”

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FDA approves new combination pill for hypertension treatment

The FDA announced Friday the approval of combination aliskiren and amlodipine as initial therapy or replacement therapy for patients with hypertension.

Approval was based on data from an 8-week, randomized, double blind, placebo-controlled, multifactorial trial that included more than 5,000 patients with mild-to-moderate hypertension. Researchers reported that combination aliskiren and amlodipine (Tekamlo, Novartis) decreased systolic/diastolic BP at trough of 14 mm Hg to 17 mm Hg/9 mm Hg to 11 mm Hg compared with 4 mm Hg to 9 mm Hg/3 mm Hg to 4 mm Hg for aliskiren alone and 9 mm Hg to 14 mm Hg/6 mm Hg to 8 mm Hg for amlodipine alone.

The combination was associated with significantly greater reductions in systolic and diastolic BP in two additional double blind, active-controlled studies in patients with moderate-to-severe hypertension. According to data from one study of 443 black patients, at 8 weeks, the treatment difference between the combination therapy and amlodipine alone was 5.2 mm Hg/3.8 mm Hg. Data from the other study of 484 patients demonstrated a 7.1 mm Hg/3.8 mm Hg treatment difference between the combination and amlodipine alone.

“Single-pill combination therapies provide a convenient treatment option while supporting physicians in addressing the complex needs of patients,” Alan Gradman, MD, professor of medicine at Temple University School of Medicine, said in a press release. “This new single-pill combination demonstrated greater BP reductions than either drug alone in clinical studies and therefore provides a new option to consider when choosing appropriate high BP therapies.”

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Pericardial fat independently associated with AF
Al Chekakie MO. J Am Coll Cardiol. 2010;56:784-788.

Data from a Journal of the American College of Cardiology study have shown that pericardial fat volume is independently associated with atrial fibrillation.

“This is the first study to examine the association between pericardial fat and AF, demonstrating a significant association with both paroxysmal and persistent AF,” the researchers wrote in their study.

To obtain this finding, they examined pericardial fat volume in 273 patients using CT, who were split into three groups: those with paroxysmal AF (n=126), persistent AF (n=71) and no history of AF (sinus rhythm group, n=76).

According to study results, patients with AF had much higher amounts of pericardial fat vs. patients in the sinus rhythm group (101.6 ± 44.1 mL vs. 76.1± 36.3 mL; P<.001). Pericardial fat volume was larger in paroxysmal AF vs. sinus rhythm group (93.9 ±39.1 mL vs. 76.1 ± 36.3 mL; P=.02), whereas those with persistent AF had larger pericardial fat volume vs. paroxysmal AF (mean difference, 21.5 mL; P=.001).

In additional study data, pericardial fat volume was associated with both persistent AF (OR=1.18; 95% CI, 1.05-1.33) and paroxysmal AF (OR=1.11; 95% CI, 1.01-1.23), an association that was independent of age, sex, hypertension, left atrial enlargement, valvular heart disease, left ventricular ejection fraction, diabetes mellitus and BMI.

“Pericardial fat volume is highly associated with paroxysmal and persistent AF independent of traditional risk factors, including left atrial enlargement,” the researchers wrote in the concluding statement of their study. “Whether pericardial fat plays a role in the pathogenesis of AF requires future investigation.”

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FDG-PET scans detected metabolic activity differences between visceral, subcutaneous adipose tissue
Christen T. J Am Coll Cardiol Img. 2010;3:843-851.
Gropler R. J Am Coll Cardiol Img. 2010;3:852-853.

Fluorodeoxyglucose-PET imaging revealed that visceral adipose tissue had increased glucose uptake vs. subcutaneous adipose tissue, according to a study.

Researchers retrospectively analyzed tissue-specific glucose uptake in vivo in clinically obtained, whole-body fluorodeoxyglucose (FDG)-PET scans in patients obese (n=31) and lean (n=26). The scans were performed for the diagnosis of primary lung cancer staging with respect to the intensity of FDG uptake in abdominal visceral adipose tissue and subcutaneous adipose tissue.

Researchers found that visceral adipose tissue had higher FDG uptake vs. subcutaneous adipose tissue (P<.0001), which was independent of age, sex, BMI, medications and comorbidities. They conducted additional research that investigated mechanisms underlying this observation in diet-induced C57BL/6 obese mice and determined that stromal vascular cells from visceral adipose tissue exhibited higher glucose uptake than those from subcutaneous adipose tissue (P=.01). Additionally, evaluation of expression of glucose transporters (GLUT1, GLUT3, and GLUT4) and hexokinases (HK1 and HK2) revealed increased expression of HK1 in visceral adipose tissue-derived vs. subcutaneous adipose tissue-derived stromal vascular cells.

“Visceral adiposity has become a therapeutic target for numerous novel pharmacologic and other strategies aimed at the improvement of dysmetabolism. Although plasma biomarkers provide one window on efficacy, availability of an imaging modality to directly probe the target tissue would help drug development programs evaluate efficacy and perform better dose selection in clinical trials,” the researchers commented in their study.

In an accompanying editorial, Robert J. Gropler, MD, and Linda R. Peterson, MD, both with the cardiovascular division of the department of internal medicine at Washington University School of Medicine in St. Louis, said there are two important contributions of this study’s findings.

“This article moves our understanding beyond the initial findings that 1) not all adipose tissue is alike and 2) adipocytes can make and respond to hormones and cytokines to realizing that adipose tissue is a complex environment composed of varying amounts of many different types of cells including the stromal vascular cell fraction,” they wrote. “[These findings] emphasize the need for the development of molecular imaging approaches that noninvasively target specific cell types and/or biological processes that comprise visceral adipose tissue and contribute to CVD.”

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Age as a Risk Factor for Stroke in Atrial Fibrillation Patients: Implications for Thromboprophylaxis
Marinigh R, Lip GY, Fiotti N, Giansante C, Lane DA.
J Am Coll Cardiol 2010;56:827-837.
Study Question: What is the impact of age on stroke risk in patients with atrial fibrillation (AF)?

Arrhythmias in a Contemporary Fontan Cohort: Prevalence and Clinical Associations in a Multicenter Cross-Sectional Study
Stephenson EA, Lu M, Berul CI, et al.
J Am Coll Cardiol 2010;56:890-896.
Study Question: What is the prevalence of arrhythmias after the Fontan procedure, and what factors are associated with their occurrence?

Hemodynamic Basis of Exercise Limitation in Patients With Heart Failure and Normal Ejection Fraction
Maeder MT, Thompson BR, Brunner-LaRocca HP, et al.
J Am Coll Cardiol 2010;56:855-863.
Study Question: What is the hemodynamic response to exercise in patients with heart failure with normal ejection fraction (HFNEF), and what is the ability of the peak early diastolic transmitral velocity to peak early diastolic annular velocity ratio (E/e') to reflect exercise hemodynamics?

Effect of Cardiac Resynchronization Therapy on Reverse Remodeling and Relation to Outcome. Multicenter Automatic Defibrillator Implantation Trial: Cardiac Resynchronization Therapy
Solomon SD, Foster E, Bourgoun M, et al., on behalf of the MADIT-CRT Investigators.
Circulation 2010;122:985-992.
Study Question: What is the effect of cardiac resynchronization therapy (CRT) on left ventricular (LV) size and function?

QT Dynamics Early After Exercise as a Predictor of Mortality
Johnson NP, Holly TA, Goldberger JJ.
Heart Rhythm 2010;7:1077-1084.
Study Question: Is the response of the QT interval to a slowing heart rate (HR) post-exercise an independent predictor of mortality?

The Effect of Warfarin Therapy on Endoleak Development After Endovascular Aneurysm Repair (EVAR) of the Abdominal Aorta
Bobadilla JL, Hoch JR, Leverson GE, Tefera G.
J Vasc Surg 2010;52:267-271.
Study Question: What is the effect of prolonged anticoagulation with warfarin on the rate of endoleaks in patient undergoing endovascular abdominal aortic aneurysm repair (EVAR)?

Genetic Variants in ABCB1 and CYP2C19 and Cardiovascular Outcomes After Treatment With Clopidogrel and Prasugrel in the TRITON–TIMI 38 Trial: A Pharmacogenetic Analysis
Mega JL, Close SL, Wiviott SD, et al.
Lancet 2010;Aug 29:[Epub ahead of print].
Study Question: What is the effect of ABCB1 polymorphism by itself and alongside variants in CYP2C19 on cardiovascular outcomes in patients treated with clopidogrel or prasugrel in the TRITON–TIMI 38 trial?

New P2Y12 Inhibitors Versus Clopidogrel in Percutaneous Coronary Intervention: A Meta-Analysis
Bellemain-Appaix A, Brieger D, Beygui F, et al.
J Am Coll Cardiol 2010;Aug 25:[Epub ahead of print].
Study Question: What is the comparative efficacy of new P2Y12 inhibitors versus clopidogrel in percutaneous coronary intervention (PCI)?

Optimal Medical Therapy for Non–ST-Segment-Elevation Acute Coronary Syndromes: Exploring Why Physicians Do Not Prescribe Evidence-Based Treatment and Why Patients Discontinue Medications After Discharge
Bagnall AJ, Yan AT, Yan RT, et al., on behalf of the Canadian Acute Coronary Syndromes Registry II Investigators.
Circ Cardiovasc Qual Outcomes 2010;Aug 17:[Epub ahead of print].
Study Question: What are the reasons for physicians not prescribing evidence-based treatments (EBTs) for patients with non–ST-segment–elevation acute coronary syndromes (NSTE ACS) and the factors determining use of these treatments after 1 year?

Effect of CYP2C19 and ABCB1 Single Nucleotide Polymorphisms on Outcomes of Treatment With Ticagrelor Versus Clopidogrel for Acute Coronary Syndromes: A Genetic Substudy of the PLATO Trial
Wallentin L, James S, Storey RF, et al.
Lancet 2010;Aug 29:[Epub ahead of print].
Study Question: What is the role of CYP2C19 and ABCB1 polymorphisms on efficacy and safety outcomes both between and within the ticagrelor and clopidogrel arms of the PLATO study?

Effectiveness of In-Laboratory High-Dose Clopidogrel Loading Versus Routine Pre-Load in Patients Undergoing Percutaneous Coronary Intervention: Results of the ARMYDA-5 PRELOAD (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) Randomized Trial
Di Sciascio G, Patti G, Pasceri V, Gatto L, Colonna G, Montinaro A, on behalf of the ARMYDA-5 PRELOAD Investigators.
J Am Coll Cardiol 2010;56:550-557.
Study Question: What is the relative safety and efficacy of 600 mg clopidogrel loading performed immediately before percutaneous coronary intervention (PCI) versus a loading dose administered 6 hours prior to PCI?

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Congressional Health Care Reform: What To Expect for CV imaging activities
by William Van Decker, MD
CV imaging has seamlessly revolutionized the care of the CV patient during my 27 years as a physician. There is absolutely no doubt in the minds of the quaternary care medical school hospitals of Philadelphia regarding the key role that CV imaging has played in the 30% reduction in CV mortality nationally within the past 10 years.

Interestingly, this outstanding success has been aided not only by the evidence-based scientific proof of the clinical therapies and outcomes CV imaging changes in sick patients (not to mention the objective reassurance to many patients triaged to medical/lifestyle management), but also to the ability of the system to have found a financial model that created access to quality CV imaging services throughout the nation in a large variety of diverse venues. Although the science and quality outcomes remain clear, the current era presents a variety of challenges for CV imaging care delivery. Some of these challenges are health care reform-based, but many are not.

Reimbursement reductions

First, there have been some sudden drops in CMS reimbursements for CV imaging physician work and office practice expense for study acquisition in the past 3 years. Unrelated to legislative health care reform, CMS’ work to bundle CPT codes performed at the same time has led to reductions in echo and nuclear cardiology physician work in image interpretation. These reductions did not take cost out of the system but rather were redistributed among the other CPT codes.

Also unrelated to health care reform, the American Medical Association delivered to CMS in 2008 the results of the Physician Practice Information Survey, a multispecialty solicited survey across all of the specialties in the house of medicine, and the basis for calculating the “in-office” practice expenses for procedures. The cardiology portion of the survey was extremely poor data with incredibly low response rate and suggested a significant decrease in cardiology practice expense from a 2005 survey, whereas all other specialty practice expense survey costs went up. This survey data placed into the mathematical practice expense equation caused a marked reduction for all four CV imaging modalities in the office setting in the 2009 Medicare physician fee schedule.

William Van Decker

In a zero-sum game, these reductions did not take cost out of the system, but instead redistributed it to the other specialties for their office practice expense, resulting in what many believe was the largest transfer of funding ever in the Medicare program. Common sense advocacy by the CV imaging societies and the American College of Cardiology have so far been unable to reverse this situation. Unfortunately, this lack of financial access stability has led to a large trend of cardiology private practices selling to hospitals and become “hospital employees.” Although a short-term solution (for a variety of reasons) was attractive to those more advanced in their careers, this is a concerning trend with fears for physician leadership of patient care and physician/patient relationships, especially for physicians early in their career.

SGR cuts

Second, both unrelated and related to congressional health care reform, is the threatened cuts to all physicians by the congressionally mandated CMS operationalized sustainable growth rate (SGR). Enacted in 2001, the SGR is a component of the conversion factor used to calculate every physician payment in the CPT fee schedule and was targeted to help “control health care costs” by decreasing physician reimbursement per service as utilization of services increased. This extremely flawed formula uses many economic parameters, most notably gross domestic product, which clearly varies independently of the real cost of medicine. Based on a 2000 benchmark, it has led to a proposed cut in physician payments every year.

Each year, Congress has stepped in to abate the cut to near neutral, adding the threatened cut to the next year and yielding a possible cut of more than 20% in 2010. Ongoing abatements by Congress have delayed this year’s cuts out to Dec. 1 (after the election process in November). The threatened additive cut to all physician services in January 2011 would likely be more than 28% for that year and 40% by 2015. Less amusingly, hospitals, nursing homes and Medicare Advantage insurance plans have been guaranteed positive “cost-of-living updates” every year. Hospitals have averaged just less than 4% every year for the past 6 years, whereas physicians have needed congressional intervention to avert marked decreases in December of every year and have been lucky (sans imaging) to average 0.5% each year.

These yearly threatened cuts create financial access instability and frustrate long-term health care planning. The AMA has a top priority of repealing the SGR, and many in Congress believe this yearly accelerating crisis cannot continue either; the question of what the trade-off in the legislative health care reform process will be remains.

Congressional health care reform

Finally, what of congressional health care reform and its effects on CV imaging? As recognized by many, the current bill is a broad brush outline and a timeline for portions of the outline to be enacted each of the next 5 years. In such a fluid situation, the angel or devil will clearly be in the evolving details. Five provisions may affect CV imaging delivery. First, all imaging labs need to be “lab accredited” (ACR, ICAL or JCAHO) by 2012 to receive Medicare payments. Second, a comparative effectiveness research program has been mandated to help clinicians make informed evidence-based choices. Some CV imaging projects have been suggested in its second and third tiers. Third, solicitations have been requested for pilot programs in appropriate use criteria clinical algorithms for efficient patient care (the ACC has submitted a proposal to this).

In addition, requests for proposals have gone out for two categories for pilots using new payment systems beyond fee for service. One category is looking for suggestions in “Episode of Care,” and the other in the nebulous grouping of “Accountable Care Organizations,” possibly linking multiple care providers in a bundled payment. The delivery of CV imaging may be affected by any of these, depending on how the requests are answered and how the pilots progress.

Some things are sure about the field of CV imaging for more than 40 years: It is innovative and flexible, has been entirely patient-centered, and has attracted passionate providers dedicated to clinical quality, diverse access venues, and improvement of the field through research. It has a variety of organizations and people dedicated to meeting the aforementioned challenges (and others that could not fit). Interesting times are likely to reinforce the downstream cost-savings of CV imaging, as we all look forward to continuing declines in national CV mortality and morbidity, which remains our No. 1 disease process.

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Intra-atrial reentrant tachycardia found lower than previous studies
Stephenson EA. J Am Coll Cardiol. 2010;56:890-896.

Rates of intra-atrial reentrant tachycardia were lower in a recent cross-sectional, multicenter study than previous studies had reported, which researchers attribute in part to changes in surgical strategy.
The Pediatric Heart Network Fontan Cross-Sectional study was composed of 520 children from seven centers who were aged 6 to 18 years. Each of the children had undergone a Fontan procedure at least 6 months before entering the study. Study data within 3 months of enrollment featured echocardiograms, electrocardiograms, exercise testing results, health status questionnaires and medical history from a review of the medical record.
Supraventricular tachycardias were reported in 9.4% of patients, whereas intra-atrial reentrant tachycardia (IART) was present in 7.3% of the population. Four to 6 years after Fontan, the hazard of IART decreased, but it increased after this time period.
Researchers identified the following independent associations of time to occurrence of IART: lower Child Health Questionnaire physical summary score (P<.001); predominant rhythm (P=.002; highest risk with paced rhythm); and type of Fontan operation (P=.037; highest risk with atriopulmonary connection).
“This contemporary cohort of Fontan survivors represents one of the largest datasets available in this unique population,” the researchers wrote. “Overall prevalence of IART (7.3%) is lower in the current cohort than in previous reports. Independent associated factors of IART development include a paced rhythm, lower functional status, and an atriopulmonary connection Fontan, a previously suspected risk factor for atrial tachycardia.”
In an accompanying editorial, George F. Van Hare, MD, from Washington University/St. Louis Children’s Hospital, St. Louis, commented on the Fontan procedure and its role in clinical practice.
“It is disappointing, but perhaps not altogether surprising, that one observes some atrial arrhythmias in patients with the external conduit Fontan,” he said. “The Fontan is not a legacy operation like the Senning procedure for transposition, and with improved survival for the Norwood/Sano operation, more and more children will be coming to surgery for Fontan completion, and so the management of these arrhythmias will continue to occupy us.”

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CRT at endocardial sites may be more effective than conventional pacing
Derval N. J Am Coll Cardiol. 2010;56:782-783. Spragg DD. J Am Coll Cardiol. 2010;56:774-781.

Left ventricular endocardial pacing yielded substantial improvements in left ventricular mechanics vs. traditional coronary sinus-based cardiac resynchronization therapy, according to study results.
The study consisted of 11 men (68 ± 5 years of age) with ischemic cardiomyopathy. Researchers measured the peak rate of LV pressure increase (dP/dtmax) at baseline, during VDD pacing at the right ventricular apex, and during biventricular pacing from the right ventricular apex and 51 ± 14 different LV endocardial sites. Electroanatomic 3-D maps with color-coded dP/dtmax response defined optimal pacing regions, delivering 85% of maximal increase in dP/dtmax.
According to study results, endocardial biventricular pacing improved dP/dtmax over right ventricular apex pacing in all patients (mean increase, 241
± 38 mm Hg/s; P < .0001). Researchers noted that among patients with pre-existing cardiac resynchronization therapy (CRT) leads, LV endocardial vs. epicardial pacing at transmural sites led to equivalent dP/dtmax values; however, dP/dtmax at the best endocardial site surpassed that achieved with the pre-implanted CRT device (mean increase, 111 ± 25 mm Hg/s; P=.004). Additionally, researchers found that optimal pacing sites were typically located in LV territories away from the infarct zone by 9.3 ± 3.6 cm.
These findings, the researchers wrote, have clear implications for how best to deliver resynchronization therapy in patients with ischemic cardiomyopathy. “In addition, our report contributes to a growing body of data about the merits of endocardial vs. epicardial LV pacing, the impact of scar burden on CRT response, and the impact of inter-patient variability in optimal LV pacing site location,” they said.
In an accompanying editorial, Nicolas Derval, MD, and Pierre Jaïs, MD, researchers based at Université Victor Segalen Bordeaux II in Pessac, France, said the findings depict some of the clinical limitations of CRT in daily practice.
“The results demonstrate the critical impact of the LV pacing site selection in optimizing hemodynamic results of CRT and the need to individualize the approach to CRT in current clinical practice,” they wrote. “To date, there is no way to identify the optimal pacing site before implantation, and the protocol used in this study is lengthy and may not be practical for routine clinical practice. However, the results … are impressive in these end-stage HF patients for whom CRT is often the last therapeutic option.”

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Elective intra-aortic balloon pump did not reduce adverse event rate after PCI
Perera D. JAMA. 2010;304:867-874.

Major adverse cardiac and CV events were not reduced in patients with severe left ventricular dysfunction and extensive coronary disease who had an intra-aortic balloon inserted before percutaneous coronary intervention, study results indicated.
The prospective, open, multicenter, randomized controlled trial was conducted in 17 tertiary referral cardiac centers in the United Kingdom between December 2005 and January 2009. Patients (n=301) had severe LV dysfunction (ejection fraction ≤30%) and extensive coronary disease (jeopardy score ≥8/12). The primary endpoint was major adverse cardiac and CV events defined as death, acute MI, cerebrovascular event or further revascularization at hospital discharge.
Of the study population, 151 received PCI with elective intra-aortic balloon pump (IABP) and 150 received PCI without IABP insertion. Major adverse cardiac and CV events occurred at hospital discharge in 15.2% (23/151) of patients with elective IABP and 16% (24/150) of those with no planned IABP. All-cause mortality at 6 months was 4.6% in the IABP group and 7.4% in the non-IABP group, with noticeably fewer major procedural complications in those with elective IABP insertion (1.3% vs. 10.7%; OR=0.11; 95% CI, 0.01-0.49).
“The study did not demonstrate a difference in [major adverse cardiac and CV events] at hospital discharge and therefore does not support routine elective IABP insertion before high-risk PCI,” the researchers said in the concluding statement of their study. “However, 12% of patients who underwent PCI without elective IABP insertion required rescue IABP support, which highlights the importance of adopting a standby IABP strategy when undertaking high-risk PCI.”
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Moderate, consistent consumption of chocolate lowered HF incidence in older women
Mostofsky E. Circ Heart Fail. 2010;doi:10.1161/circheartfailure.110.944025.
Study results published in Circulation: Heart Failure have linked moderate, habitual chocolate intake with a lower rate of HF hospitalization or death in a population of older women. However, this correlation was not observed with chocolate intake of one or more servings a day.
The study consisted of women (n=31,823) from the Swedish Mammography Cohort aged 48 to 83 years who were without diabetes or a history of HF or MI. They answered health and lifestyle questions, completed a food-frequency questionnaire and were followed for 9 years (1998 through 2006) for HF hospitalization or death.
During the follow-up, there were 379 incident HFs and 40 HF-related deaths. Compared with those with no regular chocolate consumption, multivariate-adjusted rate ratio HF for women consuming one to three servings of chocolate per month was 0.74 (95% CI, 0.58-0.95), for one to two servings per week, it was 0.68 (95% CI, 0.50-0.93) and for three to six servings a week, it was 1.09 (95% CI, 0.74-1.62). However, for women consuming one or more servings of chocolate per day, the rate ratio was 1.23 (95% CI, 0.73-2.08). The P value for the quadratic trend was .0005.
“In this population of middle-aged and elderly Swedish women, moderate, habitual chocolate intake was associated with a lower rate of HF hospitalization or death, but the protective association was not observed with intake of one or more servings per day,” researchers concluded. “Further studies are needed to confirm or refute these findings and to determine the optimal dose and type of chocolate and to clarify the mechanisms involved.”

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Title: Aspirin Is Beneficial in Hypertensive Patients With Chronic Kidney Disease: A Post-Hoc Subgroup Analysis of a Randomized Controlled Trial
Date Posted: September 6, 2010
Authors: Jardine MJ, Ninomiya T, Perkovic V, et al.
Citation: J Am Coll Cardiol 2010;56:956-965.

Study Question:
What are the benefits and risks associated with antiplatelet therapy in the chronic kidney disease population?
Methods:
The HOT (Hypertension Optimal Treatment) study randomly assigned participants with diastolic hypertension to aspirin (75 mg) or placebo. Study treatment effects were calculated using univariate proportional hazards regression models stratified by baseline estimated glomerular filtration rate (eGFR), with trends tested by adding interaction terms. Endpoints included major cardiovascular events, total mortality, and major bleeding defined as fatal, life-threatening, disabling, or requiring hospital admission.
Results:
The study included 18,597 participants treated for 3.8 years. Baseline eGFR was <60 ml/min/1.73 m2 in 3,619 participants. Mean age for those with eGFR ≥60 was 60.6 years, and for eGFR <60, mean age was 65 years. Major cardiovascular events were reduced by 9% (95% confidence interval [CI], -9% to 24%), 15% (95% CI, -17% to 39%), and 66% (95% CI, 33% to 83%) for patients with baseline eGFR of >60, 45-59, and <45 ml/min/1.73 m2, respectively (p trend = 0.03). Total mortality was reduced by 0% (95% CI, -20% to 17%), 11% (95% CI, -31% to 40%), and 49% (95% CI, 6% to 73%), respectively (p trend = 0.04). Major bleeding events were nonsignificantly greater with lower eGFR. Among every 1,000 persons with eGFR <45 ml/min/1.73 m2 treated for 3.8 years, 76 major cardiovascular events and 54 all-cause deaths will be prevented, while 27 excess major bleeds will occur.
Conclusions:
Aspirin therapy produces greater absolute reduction in major cardiovascular events and mortality in hypertensive patients with chronic kidney disease than with normal kidney function. An increased risk of major bleeding appears to be outweighed by the substantial benefits.
Perspective:
Meta-analyses of placebo controlled trials show minimal value of aspirin for prevention of coronary events and strokes, with the exception of intermediate to high risk men and women at increased stroke risk. About 10-15% of the adult population in the United States has mild chronic kidney disease, which confers an increased risk of cardiovascular events and death, but is not included in the standard cardiovascular risk scores. The benefit of aspirin in the HOT trial increased with decreasing eGFR, but became highly significant only when eGFR was <45 ml/min/1.73 m2 likely representing the incremental absolute risk in cardiovasular events with decreasing renal function.
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Title: Consensus and Future Directions on the Definition of High On-Treatment Platelet Reactivity to Adenosine Diphosphate
Date Posted: September 6, 2010
Authors: Bonello L, Tantry US, Marcucci R, et al., on behalf of the Working Group on High On-Treatment Platelet Reactivity.
Citation: J Am Coll Cardiol 2010;56:919-933.

Perspective:
The following are 10 points to remember about this white paper.

1. Adenosine diphosphate (ADP) binding to the platelet P2Y12 receptor plays an important role in sustained activation of platelet glycoprotein IIb/IIIa receptors, which supports platelet-rich thrombus formation at sites of vascular injury. An active metabolite of clopidogrel irreversibly inhibits the P2Y12 receptor.

2. The addition of clopidogrel to aspirin therapy has been proven to reduce ischemic complications in a number of clinical scenarios—especially useful in prevention of stent thrombosis. Clopidogrel could possibly be used even more effectively if inter-individual pharmacodynamic variability could be identified and managed.

3. Platelet function studies have revealed marked variability in the response to clopidogrel therapy between individuals. A high level of platelet reactivity while on clopidogrel has been associated with adverse ischemic events.

4. Insufficient generation of the clopidogrel active metabolite is the primary mechanism of clopidogrel hyporesponsiveness. Reasons for reduced active metabolite include: a) reduced intestinal absorption of drug; b) variability in the P450 isoenzyme activity responsible for prodrug metabolism, i.e., drug-drug interactions; and c) single-nucleotide polymorphisms of specific genes encoding CYP450 isoenzymes.

5. Point-of-care platelet function testing to identify high-risk patients combined with CYP2C19 genetic testing may be more effective than either test alone for identifying high-risk individuals for alternate antiplatelet therapies. Prospective, randomized clinical trials will be needed to test these and other approaches.

6. A thrombotic event while on clopidogrel therapy (clinical treatment failure) does not define clopidogrel resistance because no single drug can be expected to prevent all events. The definition of resistance or nonresponsiveness should be the failure of the antiplatelet agent to inhibit the target of its action.

7. Currently, high on-treatment platelet reactivity in the setting of percutaneous coronary intervention (PCI) has been defined by receiver-operator characteristic analyses using the following criteria: a) platelet reactivity index >50% by vasodilator stimulated phosphoprotein-phosphorylation (VASP-P) analysis, b) >235 to 240 P2Y12 reaction units by VerifyNow P2Y12 assay, c) >46% maximal 5 µmol/L ADP-induced aggregation, and d) >468 agg units/min in response to ADP by Multiplate analyzer.

8. No large-scale clinical studies have demonstrated that adjustment of antiplatelet treatment based on measures described in point #7 leads to improvement in clinical outcomes.

9. Ongoing clinical studies with VerifyNow P2Y12 assay are underway to determine whether individualization of antiplatelet therapy will improve outcomes following PCI.

10. Platelet function testing to determine antiplatelet strategy may be considered in patients with a history of stent thrombosis or patients undergoing high-risk PCI. However, pending large-scale trials, routine use of platelet function testing in patients with cardiovascular disease is not recommended.

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Cardiac Implantable Electronic Device Infections: Presentation, Management, and Patient Outcomes
Tarakji KG, Chan EJ, Cantillo DJ, et al.
Heart Rhythm 2010;7:1043-1047.
Study Question: What are the outcomes of patients with an infected pacemaker or implantable cardioverter-defibrillator?

Long-Term Outcomes of Surgical Aortic Fenestration for Complicated Acute Type B Aortic Dissections
Trimarchi S, Jonker FH, Muhs BE, et al.
J Vasc Surg 2010;52:261-266.
Study Question: What are the long-term results of suprarenal and infrarenal surgical fenestration for acute type B aortic dissections?

Gene Dosage of the Common Variant 9p21 Predicts Severity of Coronary Artery Disease
Dandona S, Stewart AF, Chen L, et al.
J Am Coll Cardiol 2010;56:479-486.
Study Question: What is the effect of 9p21 gene dosage on severity of coronary artery disease (CAD)?

Comparative Determinants of 4-Year Cardiovascular Event Rates in Stable Outpatients at Risk of or With Atherothrombosis
Bhatt DL, Eagle KA, Ohman EM, et al., on behalf of the REACH Registry Investigators.
JAMA 2010;Aug 30:[Epub ahead of print].
Study Question: Can the relative risk of cardiovascular events in stable outpatients with various initial manifestations of atherothrombosis be performed using simple clinical descriptors?

Exercise Capacity and Mortality in Older Men: A 20-Year Follow-Up Study
Kokkinos P, Myers J, Faselis C, et al.
Circulation 2010;122:790-797.
Study Question: What is the association between exercise capacity and all-cause mortality in elderly men?

The New High-Sensitivity Cardiac Troponin T Assay Improves Risk Assessment in Acute Coronary Syndromes
Lindahl B, Venge P, James S.
Am Heart J 2010;160:224-229.
Study Question: How does the new high-sensitivity cardiac troponin T (hs-cTnT) assay compare with the third-generation cTnT assay for risk assessment in acute coronary syndromes (ACS)?

Viral Endomyocardial Infection Is an Independent Predictor and Potentially Treatable Risk Factor for Graft Loss and Coronary Vasculopathy in Pediatric Cardiac Transplant Recipients
Moulik M, Breinholt JP, Dreyer WJ, et al.
J Am Coll Cardiol 2010;56:582-592.
Study Question: What is the prevalence and outcome of viral endomyocardial infection after pediatric cardiac transplantation?


Low-Dose vs Standard-Dose Unfractionated Heparin for Percutaneous Coronary Intervention in Acute Coronary Syndromes Treated With Fondaparinux: The FUTURA/OASIS-8 Randomized Trial
The FUTURA/OASIS-8 Trial Group.
JAMA 2010;Aug 31:[Epub ahead of print].
Study Question: What is the safety of two unfractionated heparin (UFH) regimens during percutaneous coronary intervention (PCI) in high-risk patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) initially treated with fondaparinux?

Randomized Comparison of Eptifibatide Versus Abciximab in Primary Percutaneous Coronary Intervention in Patients With Acute ST-Segment Elevation Myocardial Infarction: Results of the EVA-AMI Trial
Zeymer U, Margenet A, Haude M, et al.
J Am Coll Cardiol 2010;56:463-469.
Study Question: What is the efficacy of eptifibatide compared to abciximab in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI)?

Elective Intra-Aortic Balloon Counterpulsation During High-Risk Percutaneous Coronary Intervention: A Randomized Controlled Trial
Perera D, Stables R, Thomas M, et al., on behalf of the BCIS-1 Investigators.
JAMA 2010;304:867-874.
Study Question: What is the benefit of routine intra-aortic balloon pump (IABP) in patients with severe left ventricular dysfunction undergoing percutaneous coronary intervention (PCI) for extensive coronary artery disease?

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FUTURA/OASIS-8: No reduction in PCI bleeding complications with low-dose heparin in patients treated with fondaparinux
Steg P. JAMA. 2010;doi:10.1001/jama.2010.1320.

A low dose of unfractionated heparin did not reduce major periprocedural bleeding complications when compared with a standard dose in patients undergoing percutaneous coronary intervention for acute coronary syndromes treated initially with fondaparinux, results from the FUTURA/OASIS-8 study suggested.

Researchers for the prospective study selected a cohort of 2,026 patients undergoing PCI within 72 hours after the onset of ACS from a larger cohort of 3,235 high-risk patients with non-ST segment elevation ACS who were initially treated with fondaparinux (Arixtra, GlaxoSmithKline) between February 2009 and March 2010. Patients were randomly assigned to either IV low-dose unfractionated heparin (50 U/kg, n=1,024), regardless of the use of glycoprotein IIb/IIIa inhibitors, or to a standard dose of unfractionated heparin (85 U/kg, n=1,002). The standard dose was reduced to 60 U/kg in patients treated with planned glycoprotein IIb/IIIa inhibitors and was adjusted by activated clotting time. The primary outcome measure was a composite of major bleeding, minor bleeding or major vascular access-site complications up to 48 hours after PCI, with a composite secondary endpoint of major bleeding at 48 hours with death, MI or target vessel revascularization within 30 days.

According to the results, the primary endpoint occurred in 4.7% of patients in the low-dose group and in 5.8% of patients in the standard dose group (OR=0.80; 95% CI, 0.54-1.19). A slight increase in the secondary endpoint was reported in the low-dose group vs. the standard-dose group (5.8% vs. 3.9%), but the increase did not reach statistical significance. No difference in peri-PCI major bleeding between the low-dose and standard-dose groups was reported (1.4% vs. 1.2%; OR=1.14; 95% CI, 0.53-2.49), and major bleeding events up to 30 days were also similar between the low-dose and standard-dose groups (2.2% vs. 1.8%; OR=1.20; 95% CI, 0.64-2.25).

“Low-dose compared with [activated clotting time]-guided standard-dose heparin did not reduce peri-PCI bleeding and vascular access site complications,” the researchers concluded. “Catheter thromboses are rare when using unfractionated heparin for PCI in patients with non-ST segment ACS treated with fondaparinux. Therefore, patients with ACS treated with fondaparinux and undergoing PCI should receive the guideline-recommended [activated clotting time]-guided standard dose of unfractionated heparin.”
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RE-LY: Select doses of dabigatran reduced stroke, bleeding vs. warfarin
Wallentin L. Lancet. 2010;doi:10.1016/S0140-6736(10)61194-4.

New data suggest that dabigatran at 150 mg reduced stroke, at 110 mg reduced bleeding, and at both doses reduced intracranial bleeding compared with warfarin, irrespective of centers’ quality of international normalized ratio control.

Researchers performing the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial randomly assigned patients (n=18,113; 951 sites) to 110 mg or 150 mg dabigatran (Boehringer Ingelheim) twice daily vs. warfarin dose adjusted to INR 2.0 to 3.0. Study centers were placed into one of four groups based on each center’s mean time in therapeutic range (cTTR): less than 57.1%, 57.1% to 65.5%, 65.5% to 72.6%, and more than 72.6%. The median follow-up was 2 years.

During follow-up, researchers reported no significant interactions between cTTR and prevention of stroke and systemic embolism with either 110 mg or 150 mg dabigatran vs. warfarin, nor were there any significant interactions with cTTR regarding intracranial bleeding. However, a significant interaction (P=.003) was noted between cTTR and major bleeding when comparing 150 mg dabigatran with warfarin, with less bleeding events at lower cTTR but similar events at higher cTTR, whereas rates of major bleeding were lower with 110 mg dabigatran than warfarin, irrespective of cTTR.

The benefits of 150 mg dabigatran at reducing stroke, 110 mg dabigatran at reducing bleeding, and both doses at reducing intracranial bleeding vs. warfarin were consistent, irrespective of centers’ quality of INR control,” researchers concluded. “For all vascular events, non-hemorrhagic events, and mortality, advantages of dabigatran were greater at sites with poor INR control than at those with good INR control. Overall, these results show that local standards of care affect the benefits of use of new treatment alternatives.”

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UPDATE: FDA Reconsidering Midodrine Access
ACC urges FDA to reconsider process, access to the drug

The U.S. Food and Drug Administration (FDA) on Aug. 16 proposed to withdraw approval of the drug midodrine hydrochloride, used to treat orthostatic hypotension. According to the FDA, required post-approval studies that verify the clinical benefit of the drug have not been done.This is the first time that the FDA has chosen to exercise its authority to withdraw approval for a drug because of a failure to conduct adequate post-market approval studies.

In response to the announcement, the American College of Cardiology on Aug. 27 sent a letter to the FDA expressing its concern with the process, given that health care providers received "almost no notice of the impending withdrawal of the drug’s approval," which meant no time to prepare alternate courses of treatment or to investigate other options." According to the letter, "the very reason for the expedited approval of midodrine, few alternative therapies available for a life-threatening or serious disease, has not changed. No new evidence has come to light with respect to the side effects of the drug. While serious, the potential side effects of the drug are well-known to the prescribing community." The letter urged the FDA to revisit the process and to also take steps to ensure that there is true access to the drug. Read the full letter.

Update: The Associated Press on Sept. 6 reported that FDA representative Sandy Walsh "said in an emailed statement that the agency will continue to allow access to ProAmatine, also known as midodrine, 'while the necessary data is collected and the legal issues get sorted out.'" The ACC is awaiting formal confirmation from the FDA on this report. More information is expected in the coming weeks.

Physician Information: Meanwhile, when treating patients, physicians should refer to the current recommendations for the treatment of postural orthostatic tachycardia syndrome at Class IIb ( 2003 ACC/AHA/ESC Guideline for the Management of Patients With Supraventricular Arrhythmias, page 18), which remains appropriate as long as the drug is available. Should the drug become unavailable, an update will be posted and communicated expediently.
2003 ACC/AHA/ESC Guidelines for the Management of Patients With Supraventricular Arrhythmias – Page 18:
e. Treatment; PHARMACOLOGIC
Centrally acting (eg, methylphenidate, clonidine) or peripherally acting agents (eg, midodrine) have also been effectively used (171,172).
Page 19 - Recommendations for Treatment of Postural Orthostatic Tachycardia Syndrome
Treatment Recommendation Class Level of Evidence References
Pharmacologic*
Peripherally acting Midodrine IIb B (171,175)
*Combination therapy commonly required.

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Title: Late Outcomes After Carotid Artery Stenting Versus Carotid Endarterectomy. Insights From a Propensity-Matched Analysis of the Reduction of Atherothrombosis for Continued Health (REACH) Registry
Date Posted: September 7, 2010
Authors: Bangalore S, Bhatt DL, Röther J, et al.; on behalf of the REACH Registry Investigators.
Citation: Circulation 2010;Aug 30:[Epub ahead of print].

Study Question:
What is the long-term outcome of patients undergoing carotid artery stenting (CAS) compared with those undergoing carotid endarterectomy (CEA)?
Methods:
The authors compared the outcome of patients who underwent CEA or CAS and were followed in the Reduction of Atherothrombosis for Continued Health (REACH) registry. Propensity score matching was performed to adjust for the nonrandomized nature of the comparison. The primary endpoint for the analysis was defined as death or stroke at the 2-year follow-up, whereas the secondary outcome was stroke or transient ischemic attack (TIA).
Results:
Carotid revascularization was performed in 3,412 of the 68,236 patients enrolled in the registry. The majority (2,387; 70%) of these patients underwent CEA, while 1,025 (30%) underwent CAS. In a propensity-matched population (836 CAS patients with 836 CEA patients), there was no difference in the risk of death or stroke at 2 years among patients treated with CAS compared with those undergoing CEA (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.57-1.26). There was no difference in the risk of stroke or TIA in unadjusted (5.5% vs. 5.1%) or propensity-matched analysis (HR, 1.20; 95% CI, 0.73-1.96).
Conclusions:
There was no difference in the long-term outcome of patients treated with CAS versus CEA in this observational study.
Perspective:
Most of the debate on the relative safety and efficacy of CAS versus CEA has focused on early outcome, and this study is one of the few to focus on long-term outcome. The results of this study corroborate the small body of randomized data (Meier P, et al. BMJ 2010;Feb 12:[Epub ahead of print]), and the totality of data suggests that the long-term outcomes are similar with CAS and CEA.

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Title: Aspirin Is Beneficial in Hypertensive Patients With Chronic Kidney Disease: A Post-Hoc Subgroup Analysis of a Randomized Controlled Trial
Date Posted: September 6, 2010
Authors: Jardine MJ, Ninomiya T, Perkovic V, et al.
Citation: J Am Coll Cardiol 2010;56:956-965.

Study Question:
What are the benefits and risks associated with antiplatelet therapy in the chronic kidney disease population?
Methods:
The HOT (Hypertension Optimal Treatment) study randomly assigned participants with diastolic hypertension to aspirin (75 mg) or placebo. Study treatment effects were calculated using univariate proportional hazards regression models stratified by baseline estimated glomerular filtration rate (eGFR), with trends tested by adding interaction terms. Endpoints included major cardiovascular events, total mortality, and major bleeding defined as fatal, life-threatening, disabling, or requiring hospital admission.
Results:
The study included 18,597 participants treated for 3.8 years. Baseline eGFR was <60 ml/min/1.73 m2 in 3,619 participants. Mean age for those with eGFR ≥60 was 60.6 years, and for eGFR <60, mean age was 65 years. Major cardiovascular events were reduced by 9% (95% confidence interval [CI], -9% to 24%), 15% (95% CI, -17% to 39%), and 66% (95% CI, 33% to 83%) for patients with baseline eGFR of >60, 45-59, and <45 ml/min/1.73 m2, respectively (p trend = 0.03). Total mortality was reduced by 0% (95% CI, -20% to 17%), 11% (95% CI, -31% to 40%), and 49% (95% CI, 6% to 73%), respectively (p trend = 0.04). Major bleeding events were nonsignificantly greater with lower eGFR. Among every 1,000 persons with eGFR <45 ml/min/1.73 m2 treated for 3.8 years, 76 major cardiovascular events and 54 all-cause deaths will be prevented, while 27 excess major bleeds will occur.
Conclusions:
Aspirin therapy produces greater absolute reduction in major cardiovascular events and mortality in hypertensive patients with chronic kidney disease than with normal kidney function. An increased risk of major bleeding appears to be outweighed by the substantial benefits.
Perspective:
Meta-analyses of placebo controlled trials show minimal value of aspirin for prevention of coronary events and strokes, with the exception of intermediate to high risk men and women at increased stroke risk. About 10-15% of the adult population in the United States has mild chronic kidney disease, which confers an increased risk of cardiovascular events and death, but is not included in the standard cardiovascular risk scores. The benefit of aspirin in the HOT trial increased with decreasing eGFR, but became highly significant only when eGFR was <45 ml/min/1.73 m2 likely representing the incremental absolute risk in cardiovasular events with decreasing renal function.

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CUPID: AAV1/SERCA2a found safe, beneficial in patients with advanced HF

Heart Failure Society of America 14th Annual Scientific Meeting

SAN DIEGO — New data from a phase 2 trial presented here showed favorable results, including group and individual improvements, for patients with HF who were treated with AAV1/SERCA2a, a genetically targeted enzyme replacement therapy for advanced HF.


Researchers for the Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) trial set out to evaluate the safety and feasibility, as well as explore the activity and efficacy, of AAV1/SERCA2a (Mydicar, Celladon). They included patients who were aged 18 to 75 years and had an NYHA Class III or IV, ischemic or non-ischemic cardiomyopathy and left ventricular ejection fraction of 35% or less. Patients were excluded if they had anti-AAV1 neutralizing antibody titer of at least 1.2, clinically significant MI within 6 months, were likely to need HF-related surgery within the following 6 months and had an expected survival of less than 1 year.

Of the total study population (n=39; 34 men with a mean age of 60.5 years), 19 (48.7%) had ischemic cardiomyopathy, 14 (35.9%) had idiopathic cardiomyopathy and four (10.3%) had hypertensive cardiomyopathy. According to the study results, in patients treated with AAV1/SERCA2a vs. placebo, there was an improvement in group level success in the 6-minute walk test (P=.14) and end-systolic volume (P=.057); an improvement in the mean individual efficacy score (P=.052); and an improvement in duration of CV hospitalization (P=.08).

Regarding safety, Barry H. Greenberg, MD,with the University of California, San Diego, and study researcher, said in his presentation that although there were many adverse events in this very sick patient population, there was no evidence that any dose of AAV1/SERCA2a increased adverse events when compared with placebo.

“These encouraging results support further studies to determine the value of genetically targeted enzyme replacement of SERCA2a in advanced HF,” Greenberg said.

Michael R. Bristow, MD,of the University of Colorado Cardiovascular Institute, Denver, who provided commentary after the presentation, said the CUPID trial shows that AAV1/SERCA2a gene therapy can be given in a multicenter design with what appears an excellent safety profile.

In addition, Bristow said, “There is definite evidence of an efficacy signal, and I believe there is enough data here that this treatment should progress to the next stage, either phase 2b or 3. CUPID should serve as a catalyst for the development of other gene therapies for HF.” – by Brian Ellis
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Tai chi improved quality of life in patients with systolic HF

Heart Failure Society of America 14th Annual Scientific Meeting

SAN DIEGO — Twelve weeks of tai chi significantly improved quality-of-life scores in patients with systolic HF when compared with patients in an education attention control, new study data suggested.


The study included patients (n=100) with left ventricular ejection fraction of 40% or less who were split evenly into two arms: those who performed tai chi (1 hour, twice a week) for 12 weeks and those who attended an education class for the same timeframe. Researchers performed baseline, 6- and 12-week testing, which included questionnaires and functional tests. Exclusion criteria included unstable angina, MI, cardiac surgery or cardiac resynchronization therapy in the preceding 3 months, as well as cardiac arrest or new diagnosis of peripartum cardiomyopathy 6 months beforehand.

According to study data, adherence at classes was 75% in the tai chi group and 67% in the educational group. Participants of tai chi at 12 weeks experienced an improvement in median Minnesota Living with Heart Failure quality-of-life score of 19 points, whereas the score for those in the educational group did not change (P=.02). For the 6-minute walk test, the tai chi group improved its walking distance by about 35 m, whereas the control group did not improve. This difference, however, was not statistically significant, nor was the change in peak oxygen uptake between the two groups.

Additional study findings indicated that with the exception of arrhythmias, adverse events such as death, CV hospitalizations and syncope were lower in the tai chi group.

According to Gloria Yeh, MD, with Beth Israel Deaconess Medical Center in Boston, and study researcher, possible mechanisms for the favorable results of tai chi include: physical activity with training effect; the relaxation/stress-reduction, which acted on stress-related neuromodulators; the meditation and mind-body integration training, which affected autonomic tone; the breathing retraining, which decreased perceived dyspnea; and the attention and social support intrinsic to tai chi.

“Training in mind and body integration may improve quality of life and facilitate increased activity in HF,” Yeh said in her presentation. “Future research should further address physiological mechanisms, a better understanding of multiple components and define the population most likely to benefit from mind and body interventions.”

Ileana Piña, MD, professor of medicine at Case Western Reserve University, Cleveland, and Cardiology Today Editorial Board member, said in the presentation’s commentary that the greatest benefit of tai chi may actually be in the sickest groups.

Regarding other directions that Piña said she would like to see future research take, she added, “I would like to see the inclusion of more women in this age group, who have a very difficult time with cardiac rehab programs, and to do a comparison with standard exercise training type of approach. Quantifying the standard metabolic equivalent level of training I think is also important to see how much the intensity is and taking it to the community setting.” – by Brian Ellis