Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Title: Combined Use of Cryoablation and Focal Open-Irrigation Ablation for Treatment of Persistent Atrial Fibrillation: Results From a Pilot Study
Topic: Arrhythmias
Date Posted: 4/16/2010
Author(s): Mansour M, Forleo GB, Pappalardo A, et al.
Citation: Heart Rhythm 2010;7:452-458.
Clinical Trial: No
Study Question: How effective is the combination of cryoablation for pulmonary vein isolation (PVI) and radiofrequency ablation (RFA) for substrate modification in patients with persistent atrial fibrillation (AF)?
Methods: Twenty-two patients (mean age 57 years) with persistent AF underwent a three-step ablation procedure: PVI using a 23- or 28-mm cryoballoon; RFA of complex fractionated electrograms; and linear RFA along the roof, mitral isthmus, and septum. Recurrent AF during follow-up was defined as AF/flutter >30 seconds in duration after a 5-week blanking period.
Results: The median duration of cryoablation was 48 minutes and the median procedure time was 262 minutes. The efficacy of the cryoballoon for PVI was 92%. At a mean follow-up of 6 months, 86% of patients were free of recurrent AF. The only complication was transient right phrenic nerve paralysis in 9% of patients.
Conclusions: The combined use of cryoablation and RFA for persistent AF is feasible and has favorable short-term results.
Perspective: The major advantage of cryoablation over RFA is a much lower risk of esophageal injury and PV stenosis. Cryoballoons can achieve PVI with a small number of cryoenergy applications, but substrate modification and linear ablation with cryoenergy would require the use of a focal cryoablation catheter, which is not practical because of extremely long procedure times. The advantages of RFA are the relatively short application times and the ability to create drag lesions. This pilot study demonstrates that cryoablation and RFA can be combined to exploit the respective advantages of the two energy sources. Further studies are needed to compare the combined approach with conventional RFA and to establish long-term efficacy. Fred Morady, M.D., F.A.C.C.

ARMYDA-4 RELOAD Trial
New Videos on CV Imaging
[Ссылки доступны только зарегистрированным пользователям ]

[Chevychelov]

Title: Medication Adherence in Cardiovascular Disease
Topic: General Cardiology
Date Posted: 4/19/2010
Author(s): Baroletti S, Dell’Orfano H.
Citation: Circulation 2010;121:1455-1458.
Clinical Trial: No
Perspective: The following are 10 points to remember about medication adherence in cardiovascular disease.

1. Nonadherence to medications is common, with reports of >60% of cardiovascular patients being nonadherent. Less than 40% of cardiac patients report taking medications such as aspirin, beta-blockers, and statins.

2. The time period immediately after discharge is a high-risk time for nonadherence. Of patients who are adherent to medications, up to 50% of those patients will discontinue their antihypertensive medications in the 6-12 months after hospitalization. Only 40% of patients after acute coronary syndrome will continue statin therapy for 2 years (after hospitalization).

3. Primary nonadherence (not filling initial prescriptions) is associated with increased 1-year mortality after myocardial infarction (MI). Among patients who do not fill any prescriptions within 120 days of having an MI, there is an 80% increased odds of death compared to those who filled all prescriptions. Secondary nonadherence (inability to take medications correctly or refill prescriptions) is also associated with increased mortality and rehospitalization.

4. Factors related to nonadherence can be categorized into three groups: socioeconomic, communication-related, and motivational.

5. Socioeconomic factors relate to the patient’s ability to pay for medications due to lack of adequate health care coverage, unemployment, retirement, or indigence.

6. Communications-related factors that affect adherence include health illiteracy, inadequate communication including language and/or cultural barriers, substance or alcohol abuse, and mental illness.

7. Factors related to motivation can also impact adherence. Patients are less likely to adhere to a medication if there is no noticeable benefit. Unlike antibiotics or pain medications, cardiac medications such as antihypertensives, aspirin, or statins often do not make the patient feel better, thus can be perceived by the patient as not being necessary. A concern regarding adverse effects of medications may also decrease adherence for medication such as statins.

8. Potential solutions for nonadherence include intensive education by the medical team regarding the importance of cardiac medications, and should include details of the purpose of each specific medication prior to discharge. Management strategies can be tailored to the patient’s specific needs including use of generic formularies, once-per-day dosing, or combination medications. Social work involvement is recommended if health care coverage is a concern. Use of family and/or interpreter services may improve adherence if language or cultural barriers exist.

9. In the outpatient setting, follow-up 1-2 weeks after hospitalization to review medical management and assess for barriers to adherence can reduce nonadherence. Use of drug reminder charts and ongoing assessment of financial barriers, the patient’s perceptions for the use of medications, and involvement of patients in the medical decision making can also improve adherence.

10. Online information to address nonadherence includes resources for payment assistance and low-cost drugs ([Ссылки доступны только зарегистрированным пользователям ] and [Ссылки доступны только зарегистрированным пользователям ] resources related to communication to improve adherence ([Ссылки доступны только зарегистрированным пользователям ] and [Ссылки доступны только зарегистрированным пользователям ]), and resources related to motivational factors and patient education ([Ссылки доступны только зарегистрированным пользователям ] and [Ссылки доступны только зарегистрированным пользователям ]). Elizabeth A. Jackson, M.D., F.A.C.C.

[Chevychelov]

Title: Fasting Plasma Glucose in Non-Diabetic Participants and the Risk for Incident Cardiovascular Events, Diabetes, and Mortality: Results From WOSCOPS 15-Year Follow-Up
Topic: Prevention/Vascular
Date Posted: 4/21/2010
Author(s): Preiss D, Welsh P, Murray HM, et al.
Citation: Eur Heart J 2010 Apr 15. [Epub ahead of print].
Clinical Trial: No
Related Resources
Trial: The West of Scotland Coronary Prevention Study (WOSCOPS)

Study Question: Is a fasting plasma glucose (FPG) in the nondiabetic range a risk factor for long-term risk of cardiovascular disease (CVD)?
Methods: A total of 6,447 men with hypercholesterolemia (4.5-6 mmol/L) participating in the West of Scotland Coronary Prevention Study (WOSCOPS) who had a FPG but no history of CVD or diabetes (FPG <7.0 mmol/L), were followed for CV events and mortality over 14.7 years of follow-up. Patients were randomized to pravastatin 40 mg daily or placebo and followed initially for an average of 4.9 years. The primary outcome of the follow-up extension study is the relationship between FPG and CVD defined as a composite of fatal and nonfatal CVD events including coronary heart disease (CHD), stroke, and CHD deaths. Comparison of time to first event was determined by Cox proportional hazards models with Q2 as referent because of the J-shaped relationship between FPG and CVD mortality (18 mg/dl glucose = 1 mmol/L glucose).
Results: Mean age was 55 years; 2,381 nonfatal/fatal CV events and 1,244 deaths occurred. Participants were divided into fifths of baseline FPG, Q1 (≤4.3 mmol/L) to Q5 (>5.1-6.9 mmol/L). Compared with Q2 (>4.3-4.6 mmol/L), men in Q5 had no elevated risk for CV events (hazard ratio [HR], 0.95 [0.83-1.08]), or all-cause mortality (HR, 0.96) in fully adjusted analyses despite a significant risk for incident diabetes (HR, 22.05 [10.75-45.22]). After further dividing Q5 into fifths, Q5a-e, individuals in Q5e (FPG 5.8-6.9 mmol/L) were also not at increased risk of CV events or other endpoints compared with Q2. All results were similar using Q1 as the referent.
Conclusions: Elevations in FPG in the nondiabetic range were not associated with long-term risk of CV events in middle-aged men in WOSCOPS. These data suggest that the current FPG cutoff for diagnosing diabetes also appropriately identifies western men at risk of CVD.
Perspective: That an elevated fasting glucose predicts the development of diabetes over 5 years, but not CV events over the following 10 years in WOSCOPS is a surprise, considering the findings in other populations. In stark conflict is the recent report from the Atherosclerotic Risk in Communities Study (Selvin E, et al. N Engl J Med 2010;362:800-11) in which a glycated hemoglobin >5.5% is associated with an increase in risk for diabetes and coronary disease independent of other variables, and the relative risk for each 0.5% increment in glycated hemoglobin is considerable. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Implantable Cardiac Device Procedures in Older Patients: Use and In-Hospital Outcomes
Topic: Heart Failure/Transplant
Date Posted: 4/21/2010
Author(s): Swindle JP, Rich MW, McCann P, Burroughs TE, Hauptman PJ.
Citation: Arch Intern Med 2010;170:631-637.
Clinical Trial: No
Study Question: What are the age-specific practices and outcomes among patients with heart failure undergoing implantable cardioverter defibrillator (ICD) implantation?
Methods: The cohort included patients older than 18 years with a diagnosis of heart failure who underwent implantation of an ICD or cardiac resynchronization therapy (CRT) between January 1, 2004, and December 31, 2005. Data included patient demographics, comorbidities, type of device, procedural complications, length of stay, total cost of hospitalization, and hospital characteristics. Multivariate stepwise logistic regression analysis was used to identify risk factors for in-hospital mortality. Age groups were chosen to directly evaluate mortality risk among patients 80 years or older relative to younger patients, as this cohort was excluded from randomized clinical trials or was markedly under-represented.
Results: The authors identified 26,887 patients who received an implantable device. The median age was 70.0 years (17.5% were ≥80 years), 72.6% were male, and 31.3% were of nonwhite race/ethnicity. Compared with younger patients, those 80 years or older were more likely to receive CRT alone. In-hospital mortality increased from 0.7% among patients younger than 80 years to 1.2% among those ages 80-85 years and 2.2% among those older than 85 years (p < 0.001). Independent predictors of in-hospital mortality included age 80 years or older, elevated comorbidity score, inotrope use, and procedure-related complications.
Conclusions: The authors concluded that advanced age is an independent predictor of in-hospital mortality following device implantation, suggesting that additional study is needed to define criteria for appropriate device use in older patients.
Perspective: The investigators found that despite the fact that most device trials have excluded patients 80 years or older, more than one-fifth of ICD and CRT devices are implanted in this age group. Furthermore, procedure-related complication rates and in-hospital mortality are elevated in patients with advanced age. It seems that additional studies are required to clarify the appropriateness of device implantation in older patients with heart failure, as well as the merits of less invasive options and/or medical therapies. For the present, physicians need to individualize therapy based on the medical issues and patient wishes, and meaningfully discuss the potential risks and benefits of the procedure with each patient. Debabrata Mukherjee, M.D., F.A.C.C.

[Chevychelov]

Title: Caloric Sweetener Consumption and Dyslipidemia Among US Adults
Topic: Prevention/Vascular
Date Posted: 4/20/2010 4:00:00 PM
Author(s): Welsh JA, Sharma A, Abramson JL, Vaccarino V, Gillespie C, Vos MB.
Citation: JAMA 2010;303:1490-1497.
Clinical Trial: No
Related Resources
For Patients: High-Sugar Diet Linked to Cholesterol

Study Question: How do added sugars affect lipids among adults?
Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 were used for the present analysis. Dietary intake was assessed through 24-hour recalls. US adults, ages 18 years or older, who participated in the NHANES 1999-2006 survey and provided fasting blood samples were included. Adults who were pregnant, had unreliable or missing dietary data, body mass index >65, were on lipid-lowering medications, or had known diabetes were excluded. Respondents were grouped by intake of added sugars (<5%, 5% to <10%, 10% to <17.5%, 17.5% to <25%, and ≥25% of total energy intake). Outcomes of interest included mean high-density lipoprotein (HDL) cholesterol, mean triglyceride, and mean low-density lipoprotein (LDL) cholesterol. Results were weighted to be representative of the US population.
Results: A total of 6,113 respondents were included in the analysis. As sugar consumption increased, respondents were more likely to be younger, non-Hispanic blacks and have low income. Number of cigarettes was also associated with increased sugar consumption. Added sugars comprised a mean of 15.3% of calories consumed. Total energy and percent total energy from carbohydrates increased as percent of total calories from added sugars increased. Intake of added sugars was inversely proportional to percent total calories from total, polyunsaturated, monounsaturated, and saturated fats. A similar pattern was noted for protein and fiber. Adjusted mean HDL levels were inversely proportional to added sugar consumptions, while mean triglyceride levels were positively related to sugar intake. A similar pattern for LDL cholesterol was observed for women, but not for men. For adults who consumed ≥10% of calories from added sugars, the odds of low HDL were 50% to >300% compared to the reference group of <5% of calories from added sugar.
Conclusions: The investigators concluded that there is a significant correlation between added sugars and lipid levels among US adults.
Perspective: These data suggest that health care providers should counsel patients to avoid significant intake of sweetened foods, as an important cardiovascular prevention measure. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Treatment and Risk in Heart Failure: Gaps in Evidence or Quality?
Topic: Heart Failure/Transplant
Date Posted: 4/20/2010
Author(s): Peterson PN, Rumsfeld JS, Liang L, et al., on behalf of the American Heart Association Get With The Guidelines-Heart Failure Program.
Citation: Circ Cardiovasc Qual Outcomes 2010;Apr 13:[Epub ahead of print].
Clinical Trial: No
Study Question: Does the paradoxical inverse relationship between risk and treatment of heart failure patients reflect larger gaps in care quality or higher rates of treatment contraindications in patients with higher risk?
Methods: The study cohort was comprised of 18,307 patients with left ventricular systolic dysfunction surviving hospitalization between January 2005 and June 2007 from 194 hospitals participating in the Get With The Guidelines (GWTG)–Heart Failure Program. Patients were categorized according to their estimated risk for in-hospital mortality using a validated risk score. The proportion of patients with documented contraindications to angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers and beta-blockers as well as the use of these medications among patients without contraindications at hospital discharge was determined across levels of risk.
Results: For each therapy, the proportion of patients with contraindications was significantly higher with increasing patient risk (p < 0.001 for each). However, even after excluding those with contraindications, the use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers and beta-blockers was significantly lower with increasing risk (p < 0.001 for each).
Conclusions: The use of evidence-based therapies is lower in patients with heart failure at higher risk of mortality both because of higher rates of contraindications to therapy and lower rates of use among eligible patients. Optimizing heart failure outcomes will require both the expansion of the evidence base for treating the highest-risk patients as well as the development of effective strategies to assure that eligible high-risk patients receive all appropriate therapies.
Perspective: The absolute benefits of an intervention are proportional to the patient’s underlying risk. These are sobering data, suggesting that we often fail to treat those at greatest risk––those who stand to benefit the most from treatment. Although contraindications were shown in this study to account for some failure of therapy among higher-risk patients, risk itself also appeared to be responsible for failure to utilize evidence-based therapies. Experience suggests that not all patients fit into checked boxes, and not all failures to treat are necessarily unjustified (even if the appropriate contraindication was not documented). However, this study should give pause, and serve to remind us that risk itself should be considered an indication, not a contraindication, to therapy. David S. Bach, M.D., F.A.C.C.

[Chevychelov]

Title: Evidence of Disparity in the Application of Quality Improvement Efforts for the Treatment of Acute Myocardial Infarction: The American College of Cardiology’s Guidelines Applied in Practice Initiative in Michigan
Topic: Heart Failure/Transplant
Date Posted: 4/20/2010
Author(s): Olomu AB, Grzybowski M, Ramanath VS, et al., on behalf of the American College of Cardiology Foundation Guidelines Applied in Practice Steering Committee.
Citation: Am Heart J 2010;159:377-384.
Clinical Trial: No
Study Question: Did the structured initiative for improving care of patients with acute myocardial infarction (Guidelines Applied in Practice [GAP]) lead to comparable care of white and nonwhite patients admitted to GAP hospitals in Michigan?
Methods: Medicare patients were comprised of two cohorts: 1) those admitted before GAP implementation (n = 1,368), and 2) those admitted after GAP implementation (n = 1,489). The main outcome measure was adherence to guideline-based medications and recommendations and use of the GAP discharge tool. Chi squared and Fisher exact tests were used to determine differences between white patients (n = 2,367) and nonwhite patients (n = 490).
Results: In-hospital GAP tool and aspirin use significantly improved for white and nonwhite patients. Beta-blocker use in-hospital improved significantly for nonwhite patients only (66% vs. 83.3%; p = 0.04). At discharge, nonwhite patients were 28% and 64% less likely than white patients to have had the GAP discharge tool used (p = 0.004) and receive smoking cessation counseling (p < 0.001), respectively. Among white patients, GAP improved discharge prescription rates for aspirin by 10.8% (p < 0.001) and beta-blockers by 7.0% (p = 0.047). Nonwhite patients’ aspirin prescriptions increased by 1.0% and beta-blocker prescriptions decreased by 6.0% (both P values were nonsignificant).
Conclusions: The GAP program led to significant increases in rates of evidence-based care in both white and nonwhite Medicare patients. However, nonwhite patients received less frequent use of the discharge tool and smoking cessation counseling. Policies designed to reduce racial disparities in health care must address disparity in the delivery of quality improvement programs.
Perspective: There was not adequate sample size to determine if the evidence for racial disparities, as found in the GAP program, occurred as a result of different levels of care by practitioners within the same institutions. As the authors suggest, it is highly likely that the findings represent decreased availability of resources to fully implement the GAP discharge tool in those hospitals serving a higher percentage of nonwhite patients, and the nonwhite patients are more likely to be cared for in lower quality performing hospitals. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Erectile Dysfunction Predicts Cardiovascular Events in High-Risk Patients Receiving Telmisartan, Ramipril, or Both: The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (ONTARGET/TRANSCEND) Trials
Topic: General Cardiology
Date Posted: 4/20/2010
Author(s): Bцhm M, Baumhдkel M, Teo K, et al., on behalf of the ONTARGET/TRANSCEND Erectile Dysfunction Substudy Investigators.
Citation: Circulation 2010;121:1439-1446.
Clinical Trial: No
Related Resources
Trial: ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET)
Trial: Telmisartan Randomised Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND)

Study Question: Is erectile dysfunction (ED) predictive of mortality and cardiovascular (CV) outcomes in high-risk men?
Methods: In a prespecified substudy, 1,549 patients underwent double-blind randomization, with 400 participants assigned to receive ramipril, 395 telmisartan, and 381 the combination thereof (ONTARGET), as well as 171 participants assigned to receive telmisartan and 202 placebo (TRANSCEND). ED was evaluated at baseline, at 2-year follow-up, and at the visit before closeout. The effect of baseline erectile function on the primary composite outcome (death due to CV causes, myocardial infarction [MI], stroke, or hospitalization for heart failure) and all-cause mortality was assessed with Cox regression analysis, stratifying by treatment allocation to account for combining the two studies and adjusting for age and clinical variables. Hazard ratios with 95% confidence intervals were used to examine the relationship of the severity of ED with subsequent clinical outcomes.
Results: Approximately 55% had ED and 45% had no ED or mild ED; mean blood pressure was 140/81 mm Hg; 40% of those with ED had diabetes compared to 26% in those with no/mild ED (p < 0.0001), and there were no differences between groups for ankle-brachial index or medications including beta-blockers (57.5%). All-cause deaths occurred in 11.3% of the patients who reported ED at baseline, but only in 5.6% of patients with no/mild ED at baseline (hazard ratio [HR], 2.04; p = 0.0002). ED was predictive of the composite primary outcome that occurred in 16.2% with ED compared to 10.3% with no/mild ED (HR, 1.62; p = 0.001), which was dominated by CV death (HR, 1.93; p = 0.016), and MI (HR, 2.02; p = 0.017). The study medications did not influence the course or development of ED.
Conclusions: ED is a potent predictor of all-cause death and the composite of CV death, MI, stroke, and heart failure in men with CV disease. Trial treatment did not significantly improve or worsen ED.
Perspective: ED was very common in this study. Interestingly, it did not vary with use of beta-blockers at baseline, and there was no impact of telmisartan or ramipril. ED was highly predictive of CV death and MI, but not stroke (regardless of adjustment for age and blood pressure) or heart failure when these variables were evaluated independently. Total mortality increased with increasing degrees of ED. While ED is associated with endothelial dysfunction and atherosclerosis, it is not clear as to why it would impact total mortality. Melvyn Rubenfire, M.D., F.A.C.C

[Chevychelov]

Title: Differences Between Beta-Blockers in Patients With Chronic Heart Failure and Chronic Obstructive Pulmonary Disease: A Randomized Crossover Trial
Topic: Heart Failure/Transplant
Date Posted: 4/19/2010 5:00:00 PM
Author(s): Jabbour A, Macdonald PS, Keogh AM, et al.
Citation: J Am Coll Cardiol 2010;55:1780-1787.
Clinical Trial: yes
Study Question: What are the respiratory, hemodynamic, and clinical effects of switching between β1-selective and nonselective beta-blockers in patients with chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD)?
Methods: A randomized, open-label, triple-crossover trial involving 51 subjects receiving optimal therapy for CHF was conducted in two Australian teaching hospitals. Subjects were a mean age of 66 years (standard deviation [SD] 12 years) and had New York Heart Association (NYHA) functional class I (n = 6), II (n = 29), or III (n = 16); and left ventricular ejection fraction (mean of 37%, SD 10%); 35 had coexistent COPD. Subjects received each beta-blocker, dose-matched, for 6 weeks before resuming their original beta-blocker. Echocardiography, N-terminal prohormone brain natriuretic peptide (NT-BNP), central augmented pressure from pulse waveform analysis, respiratory function testing, 6-minute walk distance, and NYHA functional class were assessed at each visit.
Results: The investigators found that NT-BNP was significantly lower with carvedilol than with metoprolol or bisoprolol (mean: carvedilol 1001 [95% confidence interval (CI), 633-1367] ng/L; metoprolol 1371 [95% CI, 778-1964] ng/L; bisoprolol 1349 [95% CI, 782-1916] ng/L; p < 0.01), and returned to baseline level on recommencement of the initial beta-blocker. Central augmented pressure (a measure of pulsatile afterload) was lowest with carvedilol (carvedilol 9.9 [95% CI, 7.7-12.2] mm Hg; metoprolol 11.5 [95% CI, 9.3-13.8] mm Hg; bisoprolol 12.2 [95% CI, 9.6-14.7] mm Hg; p < 0.05). In subjects with COPD, forced expiratory volume in 1 second was lowest with carvedilol and highest with bisoprolol (carvedilol 1.85 [95% CI, 1.67-2.03] L/s; metoprolol 1.94 [95% CI, 1.73-2.14] L/s; bisoprolol 2.0 [1.79-2.22] L/s; p < 0.001). The NYHA functional class, 6-minute walk distance, and left ventricular ejection fraction did not change. The beta-blocker switches were well tolerated.
Conclusions: The authors concluded that switching between β1-selective beta-blockers and the nonselective beta-blocker carvedilol is well tolerated, but results in demonstrable changes in airway function, most marked in patients with COPD. Switching from β1-selective beta-blockers to carvedilol causes short-term reduction of central augmented pressure and NT-BNP.
Perspective: Managing two conditions simultaneously involves trade-offs. Typically, HF specialists have chosen bisoprolol first-line in patients with clinically significant reactive airways disease such as asthma. In this study, carvedilol was associated with a 'better' hemodynamic response, as evidenced by lower NT-BNP and central aortic pressure, but associated with poorer forced expiratory volume in 1 second (FEV1) responses. However, the poorer FEV1 responses were not associated with worsening NYHA functional class or 6-minute walk test. Larger blinded randomized studies are needed to determine which beta-blocker has the best clinical outcome in CHF patients with COPD. Ragavendra R. Baliga, M.B.B.S.

Title: Combined Heart Failure Device Diagnostics Identify Patients at Higher Risk of Subsequent Heart Failure Hospitalizations: Results From PARTNERS HF (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients With Heart Failure) Study
Topic: Heart Failure/Transplant
Date Posted: 4/19/2010 5:00:00 PM
Author(s): Whellan DJ, Ousdigian KT, Al-Khatib SM, et al., on behalf of for the PARTNERS Study Investigators.
Citation: J Am Coll Cardiol 2010;55:1803-1810.
Clinical Trial: No
Related Resources
JACC Article: Combined Heart Failure Device Diagnostics Identify Patients at Higher Risk of Subsequent Heart Failure Hospitalizations: Results From PARTNERS HF Study

Study Question: What is the ability of combined heart failure (HF) device diagnostic information to predict clinical deterioration of HF in patients with systolic left ventricular dysfunction?
Methods: The investigators analyzed data from 694 cardiac resynchronization therapy (CRT) defibrillator patients from the PARTNERS HF (Program to Access and Review Trending Information and Evaluate Correlation to Symptoms in Patients With Heart Failure) who were followed for 11.7 ± 2 months. The PARTNERS HF was a prospective, multicenter, observational study in patients receiving CRT implantable cardioverter-defibrillators. HF events were independently adjudicated. The investigators developed a combined HF device diagnostic algorithm on an independent data set. The algorithm was considered positive if a patient had two of the following abnormal criteria during a 1-month period: long atrial fibrillation duration, rapid ventricular rate during atrial fibrillation, high fluid index (≥60), low patient activity, abnormal autonomics (high night heart rate or low heart rate variability), or notable device therapy (low CRT pacing or implantable cardioverter-defibrillator shocks), or if they only had a very high (≥100) fluid index. The investigators used univariate and multivariable analyses to determine predictors of subsequent HF events within a month.
Results: The investigators found that 90 patients had 141 adjudicated HF hospitalizations with pulmonary congestion at least 60 days after implantation. Patients with a positive combined HF device diagnostics had a 5.5-fold increased risk of HF hospitalization with pulmonary signs or symptoms within the next month (hazard ratio, 5.5; 95% confidence interval, 3.4-8.8; p < 0.0001), and the risk remained high after adjusting for clinical variables (hazard ratio, 4.8; 95% confidence interval, 2.9-8.1; p < 0.0001).
Conclusions: The authors concluded that monthly review of HF device diagnostic data identifies patients at a higher risk of HF hospitalizations within the subsequent month.
Perspective: Although this was not a blinded study, this is an important study because it identifies patients most likely to have HF hospitalizations. The ability to predict hospitalizations will allow HF disease management programs to focus on highest risk patients to reduce hospitalizations and associated costs. A large blinded randomized study would be needed to validate the findings of this study, whether more frequent analysis of the data improves the ability to risk stratify, and how these findings compare with data obtained from other implantable hemodynamic device monitors (see Circulation 2010;121:1086-95). Ragavendra R. Baliga, M.B.B.S.

[Chevychelov]

Title: Lipid Re-screening: What Is the Best Measure and Interval?
Topic: Prevention/Vascular
Date Posted: 4/22/2010
Author(s): Takahashi O, Glasziou PP, Perera R, et al.
Citation: Heart 2010;96:448-452.
Clinical Trial: No
Study Question: What is the long-term true change variation (‘signal’) and short-term within-person variation (‘noise’) of the different lipid measures and the optimal interval for lipid re-screening?
Methods: A retrospective cohort study was conducted from 2005 to 2008 at a medical health check-up program in Tokyo. A total of 15,810 apparently healthy Japanese adults not taking cholesterol-lowering drugs at baseline underwent an annual measurement of fasting serum lipids. Measurement of the ratio of long-term true change variation (‘signal’) to the short-term within-person variation (‘noise’) was determined for individual lipid components and the ratio of total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) to HDL-C.
Results: At baseline, 53% were male; mean age was 49 years; body mass index (BMI) was 22.5 kg/m2 [standard deviation (SD) (3.2)]; mean TC level 5.3 mmol/L (0.9 mmol/L), triglycerides 1.1 (0.8); and mean ratio TC/HDL and LDL/HDL level at baseline were 3.5 (1.0) and 2.0 (0.8), respectively. Each had annual check-ups over 4 years. Short-term within-person variations of TC, LDL, HDL, TC/HDL, and LDL/HDL were 0.12 (coefficient of variation [CV] 6.4%), 0.08 (CV 9.4%), 0.02 (CV 8.0%) mmol2/L2, 0.08 (CV 7.9%), and 0.05 (CV 10.6%), respectively. The ratio of signal-to-noise at 3 years was largest for TC/HDL (1.6), followed by LDL/HDL (1.5), LDL (0.99), TC (0.8), and HDL (0.7), suggesting that cholesterol ratios are more sensitive re-screening measures.
Conclusions: The signal-to-noise ratios of standard single lipid measures (TC, LDL, and HDL) are weak over 3 years, and decisions based on these measures are potentially misleading. The ratios, TC/HDL and LDL/HDL, seem to be better measures for monitoring assessments. The lipid re-screening interval should be >3 years for those not taking cholesterol-lowering drugs.
Perspective: The results support the use of TC/HDL as the preferred lipid parameter for risk stratification, but are not generalizable. This Japanese cohort had a low BMI and low-risk lipid profile. The degree to which increasing BMI and triglycerides would alter the conclusion is not known, but may be considerable. The ratio of LDL to HDL needs to be obtained fasting, and in most cohort studies, has less ability than the TC/HDL to discriminate risk of cardiovascular events. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Gadolinium-Enhanced Magnetic Resonance Angiography for Pulmonary Embolism: A Multicenter Prospective Study (PIOPED III)
Topic: Noninvasive Cardiology
Date Posted: 4/21/2010
Author(s): Stein PD, Chenevert TL, Fowler SE, et al., on behalf of the PIOPED III (Prospective Investigation of Pulmonary Embolism Diagnosis III) Investigators.
Citation: Ann Intern Med 2010;152:434-443.
Clinical Trial: No
Related Resources
Trial: Prospective Investigation of Pulmonary Embolism Diagnosis Study (PIOPED)

Study Question: What is the accuracy of gadolinium-enhanced magnetic resonance angiography, with or without magnetic resonance venography, for diagnosing pulmonary embolism?
Methods: In a prospective, multicenter study performed between April 2006 and September 2008, 371 adult patients at seven hospitals evaluated for pulmonary embolism were studied. Independently read magnetic resonance imaging was compared with the reference standard for diagnosis. (The reference standard used various tests, including computed tomographic angiography and venography, ventilation–perfusion lung scan, venous ultrasonography, D-dimer assay, and clinical assessment.)
Results: Magnetic resonance angiography, averaged across centers, was technically inadequate in 92 of 371 (25%) patients; the proportion of technically inadequate images ranged from 11% to 52% at various centers. Including patients with technically inadequate images, magnetic resonance angiography identified 59 of 104 (57%) patients with pulmonary embolism. Technically adequate magnetic resonance angiography had a sensitivity of 78% and a specificity of 99%. Technically adequate magnetic resonance angiography and venography had a sensitivity of 92% and a specificity of 96%, but 52% of patients (194 of 370) had technically inadequate results. Of note, a high proportion of patients with suspected embolism was not eligible or declined to participate.
Conclusions: The authors concluded that magnetic resonance pulmonary angiography should be considered only at centers that routinely perform it well, and only for patients for whom standard tests are contraindicated. In patients with technically adequate images, combined magnetic resonance pulmonary angiography and magnetic resonance venography have a higher sensitivity than does magnetic resonance pulmonary angiography alone, but it is more difficult to obtain technically adequate images with the two procedures.
Perspective: This is a realistic look at the application of a newer diagnostic imaging tool to a common clinical problem that has good (albeit imperfect) existing methods for diagnosis. The important strengths of magnetic resonance imaging were countered in this study by technically inadequate images in many patients who underwent the test, and by a substantial number of patients who––in this clinical setting––were ineligible for, or who declined to have the test. David S. Bach, M.D., F.A.C.C.

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Title: Clinical Relevance of Clopidogrel Unresponsiveness During Elective Coronary Stenting: Experience With the Point-of-Care Platelet Function Assay-100 C/ADP
Topic: Interventional Cardiology
Date Posted: 4/21/2010
Author(s): Moerenhout CM, Claeys MJ, Haine S, et al.
Citation: Am Heart J 2010;159:434-438.
Clinical Trial: No
Study Question: What is the clinical impact of unresponsiveness to clopidogrel in patients undergoing elective coronary artery stenting?
Methods: The authors evaluated the association between preprocedural platelet inhibition and postprocedural myonecrosis in 250 patients undergoing elective percutaneous coronary intervention (PCI). Platelet aggregation testing was performed at the time of the intervention using a point-of-care assay, the Platelet Function Assay (PFA-100C/ADP; Dade-Behring, Deerfield, IL). Nonresponse to clopidogrel was defined as a PFA closure time of <71 seconds under dual oral antiplatelet therapy. Postprocedural myonecrosis was defined as an elevation in creatine kinase-MB >1x the upper limit of normal 12-24 hours after intervention. The secondary endpoint was a composite endpoint of major adverse cardiac events (MACE) including death, myocardial infarction, and stent thrombosis at 6 months.
Results: Preprocedural PFA closure time was determined in 242 patients and ranged from 31 to 300 seconds, with a mean value of 147 seconds. Seventeen (7%) patients were nonresponders. Post-PCI myonecrosis occurred in 29 patients (12%) and was more common in nonresponders than in normal responders (29% vs. 11%, p = 0.04). This difference remained significant after adjusting for baseline differences. MACE at 6 months occurred in 13 patients and was comprised of one sudden death possibly related to stent thrombosis and 12 post-PCI myocardial infarctions. MACE was nonsignificantly more common in the nonresponder group (12% vs. 5%, respectively; p = 0.2).
Conclusions: The investigators concluded that unresponsiveness to clopidogrel as assessed by PFA-100C/ADP is an independent risk factor for thrombotic complications after coronary intervention.
Perspective: This small underpowered study suggests that patients who are poorly responsive to clopidogrel are more likely to have myonecrosis after elective PCI. While the study did not find a significant difference in postprocedural MI, this was probably related to the small study size. Larger studies are needed to confirm these findings and to assess the utility of using either prasugrel or larger doses of clopidogrel in patients who are nonresponders to clopidogrel. Hitinder S. Gurm, M.B.B.S., F.A.C.C.

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Title: B-Type Natriuretic Peptide and the Effect of Ranolazine in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes: Observations From the MERLIN–TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary–Thrombolysis In Myocardial Infarction 36) Trial
Topic: General Cardiology
Date Posted: 4/23/2010
Author(s): Morrow DA, Scirica BM, Sabatine MS, et al.
Citation: J Am Coll Cardiol 2010;55:1189-1196.
Clinical Trial: No
Related Resources
JACC Article: B-Type Natriuretic Peptide and the Effect of Ranolazine in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes: Observations From the MERLIN–TIMI 36 Trial
Trial: Metabolic Efficiency With Ranolazine for Less Ischemia in NSTE-ACS (MERLIN-TIMI 36)

Study Question: What is the interaction between B-type natriuretic peptide (BNP) and the effect of ranolazine in patients with acute coronary syndromes (ACS)?
Methods: The investigators measured plasma BNP in all available baseline samples (n = 4,543) among patients with non–ST-segment elevation ACS randomized to ranolazine or placebo in the MERLIN–TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST Elevation Acute Coronary–Thrombolysis In Myocardial Infarction 36) trial and followed them for a mean of 343 days. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and recurrent ischemia. BNP elevation was defined as >80 pg/ml.
Results: Patients with elevated BNP (n = 1,935) were at significantly higher risk of the primary trial endpoint (26.4% vs. 20.4%, p < 0.0001), cardiovascular death (8.0% vs. 2.1%, p < 0.001), and myocardial infarction (10.6% vs. 5.8%, p < 0.001) at 1 year. In patients with BNP >80 pg/ml, ranolazine reduced the primary endpoint (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.66-0.94; p = 0.009). The effect of ranolazine in patients with BNP >80 pg/ml was directionally similar for recurrent ischemia (HR, 0.78; 95% CI, 0.62-0.98; p = 0.04) and cardiovascular death or myocardial infarction (HR, 0.83; 95% CI, 0.66-1.05; p = 0.12). There was no detectable effect in those with low BNP (p interaction value = 0.05).
Conclusions: The authors concluded that ranolazine may have enhanced efficacy in high-risk patients with ACS identified by increased BNP.
Perspective: This study confirms prior observations that patients with ACS who have an elevated BNP concentration at baseline are at substantially higher risk of adverse outcomes, including cardiovascular death, heart failure, recurrent ischemic events, tachyarrhythmias, and reduced exercise capacity. In such high-risk patients, ranolazine had a significant benefit, with a reduction in the primary endpoint of cardiovascular death, myocardial infarction, or recurrent ischemia. This potential benefit of ranolazine needs to be prospectively evaluated. Debabrata Mukherjee, M.D., F.A.C.C.

Title: Role of Cardiac Magnetic Resonance Imaging in the Detection of Cardiac Amyloidosis
Topic: Noninvasive Cardiology
Date Posted: 4/22/2010
Author(s): Syed IS, Glockner JF, Feng D, et al.
Citation: JACC Cardiovasc Imaging 2010;3:155-164.
Clinical Trial: No
Related Resources
JACC Cardiovasc Imaging Article: Role of Cardiac Magnetic Resonance Imaging in the Detection of Cardiac Amyloidosis

Study Question: What is the role of cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE) for identification of patients with cardiac amyloidosis (CA)?
Methods: LGE-CMR was performed in 120 patients with amyloidosis, 35 of whom had cardiac biopsy and the remaining 85 categorized as with or without CA by echocardiographic criteria (>12 mm mean wall thickness). LGE-CMR was characterized as global transmural, global subendocardial, patchy focal LGE, and suboptimal nulling.
Results: For the 35 patients with biopsy-proven CA, LGE was global in 29, suboptimal nulling in three, focal patchy in two and absent in only one patient. Left ventricular (LV) wall thickness by echo was >12 mm in 32 patients (91%). Cardiac histology revealed moderate to severe interstitial amyloid in 28, 25 (89%) of whom had global LGE. Three of five patients with ≤ mild interstitial amyloid had nonglobal LGE. In the 85 patients without cardiac biopsy, the echocardiogram suggested amyloid in 49, 42 of whom had LGE, including 18 with global transmural and eight with global subendocardial, 10 with suboptimal nulling, and a patchy pattern in six. Seven patients with echocardiographic wall thickness >12 mm had no LGE. Of the 36 patients without echo evidence of CA, 17 (47%) had LGE, which was global subendocardial in three, suboptimal nulling in six, and patchy in eight patients. LGE on CMR was associated with higher LV mass index and greater LV and right ventricular wall thickness, and a higher likelihood of low-voltage electrocardiogram.
Conclusions: LGE on CMR is common in patients with CA and appears related to the magnitude of interstitial amyloid deposition. Multiple patterns including global transmural and subendocardial as well as suboptimal myocardial nulling and focal patchy LGE are observed, and the presence and pattern of LGE is associated with morphological and clinical markers of prognosis.
Perspective: This is one of several fairly recent studies using LGE on CMR as a marker of cardiac amyloid in comparison with either cardiac histology or echocardiography findings. This study identifies several different LGE patterns, each of which was associated with CA on biopsy or echocardiography. Previous smaller studies have suggested a more specific pattern of global subendocardial involvement. It should be emphasized that the pattern detected may be technique dependent and that standardization of contrast administration, pulse sequencing, and timing of imaging for LGE may play a role in the overall detection rate of LGE. An important message from this study is that the pattern of amyloid correlated with the magnitude of interstitial infiltration on biopsy and also with a number of morphologic and biochemical markers of the presence and prognosis of patients with cardiac amyloid. In direct comparison to echocardiography, there clearly was a subset of patients in whom no echocardiographic wall thickening was detected yet LGE was present, suggesting a greater sensitivity of LGE-CMR for detecting early phases of cardiac amyloid than is available from echocardiographic wall thickness alone. Of note, more detailed parameters of myocardial deformation such as strain or detailed diastolic function parameters were not used in this study and may have allowed detection of more patients by echocardiography. Finally, it should be emphasized that all patients in this study had known amyloidosis and that the population was not heterogeneous, including patients with coronary disease, hypertensive vascular disease, or other forms of infiltrative cardiomyopathy, etc. William F. Armstrong, M.D., F.A.C.C.

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Title: Dronedarone for Atrial Fibrillation: Have We Expanded the Antiarrhythmic Armamentarium?
Topic: Arrhythmias
Date Posted: 4/22/2010
Author(s): Singh D, Cingolani E, Diamond GA, Kaul S.
Citation: J Am Coll Cardiol 2010;55:1569-1576.
Clinical Trial: No
Related Resources
JACC Article: Dronedarone for Atrial Fibrillation: Have We Expanded the Antiarrhythmic Armamentarium?

Conclusions: The following are 10 points to remember from this review of dronedarone:

1. Dronedarone was designed to eliminate the organ toxicity of amiodarone (its parent compound) without compromising efficacy.

2. Dronedarone is metabolized by CYP3A4, and the dosage of drugs that inhibit this cytochrome should be adjusted to avoid overexposure to dronedarone.

3. The half-life of dronedarone is 30 hours compared to approximately 2 months for amiodarone.

4. Dronedarone inhibits tubular secretion of creatinine and causes a 10-15% increase in serum creatinine without reducing the glomerular filtration rate.

5. The pooled results of four randomized trials demonstrate that dronedarone prevented a recurrence of atrial fibrillation (AF) in 57% of patients, compared to 46% with placebo.

6. In a randomized trial, dronedarone was 50% less effective than amiodarone for preventing AF and was not significantly better tolerated.

7. Dronedarone increases the risk of death in patients with severe or recently decompensated heart failure (HF).

8. In a clinical trial, dronedarone was associated with a 24% reduction in the risk of cardiovascular hospitalization and did not significantly affect mortality.

9. The main side effects of dronedarone are diarrhea, nausea, and rash, and there is no evidence that dronedarone causes proarrhythmia or endocrine, neurological, or pulmonary toxicity.

10. The available data support the limited use of dronedarone in patients without recently decompensated HF, mostly as a second-line agent as an alternative to amiodarone.
Perspective: It is clear that dronedarone is not what many had hoped for, namely ‘a safe amiodarone.’ Freedom from organ toxicity comes with the price of lower efficacy than amiodarone. This, along with the high cost ($9/day retail), may limit its use in clinical practice. Fred Morady, M.D., F.A.C.C.

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Title: Efficacy of Rosuvastatin Among Men and Women With Moderate Chronic Kidney Disease and Elevated High-Sensitivity C-Reactive Protein: A Secondary Analysis From the JUPITER (Justification for the Use of Statins in Prevention-an Intervention Trial Evaluating Rosuvastatin) Trial
Topic: Prevention/Vascular
Date Posted: 4/23/2010
Author(s): Ridker PM, MacFadyen J, Cressman M, Glynn RJ.
Citation: J Am Coll Cardiol 2010;55:1266-1273.
Clinical Trial: No
Related Resources
JACC Article: Efficacy of Rosuvastatin Among Men and Women With Moderate Chronic Kidney Disease and Elevated High-Sensitivity C-Reactive Protein: A Secondary Analysis From the JUPITER Trial
Trial: Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER)

Study Question: What is the efficacy of statin therapy in primary prevention among individuals with moderate chronic kidney disease (CKD)?
Methods: The authors performed a secondary analysis within JUPITER (Justification for the Use of Statins in Prevention–an Intervention Trial Evaluating Rosuvastatin) comparing cardiovascular and mortality outcomes among those with moderate CKD at study entry (n = 3,267) with those with baseline estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 (n = 14,528). JUPITER is the primary prevention trial of rosuvastatin 20 mg compared with placebo among men and women free of cardiovascular disease who had low-density lipoprotein cholesterol (LDL-C) <130 mg/dl and high-sensitivity C-reactive protein (hs-CRP) ≥2 mg/L.
Results: Study participants with moderate CKD were older (70 years vs. 65 years), more likely to be female, more likely to have a family history of premature atherothrombosis, and less likely to smoke. Among those with reduced eGFR, 3,253 had stage 3 impairment (eGFR between 30 and 59 ml/min/1.73 m2) and 14 had stage 4 impairment (eGFR between 15 and 29 ml/min/1.73 m2). Median follow-up was 1.9 years (maximum 5 years). Compared with an eGFR ≥60 ml/min/1.73 m2, JUPITER participants with moderate CKD had higher vascular event rates (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.23-1.92; p = 0.0002). Among those with moderate CKD, rosuvastatin was associated with a 45% reduction in risk of myocardial infarction, stroke, hospital stay for unstable angina, arterial revascularization, or confirmed cardiovascular death (HR, 0.55; 95% CI, 0.38-0.82; p = 0.002) and a 44% reduction in all-cause mortality (HR, 0.56; 95% CI, 0.37-0.85; p = 0.005). Median LDL-C and hs-CRP reductions as well as side effect profiles associated with rosuvastatin were similar among those with and without CKD. Median eGFR at 12 months was marginally improved among those allocated to rosuvastatin, as compared with placebo.
Conclusions: Rosuvastatin reduces first cardiovascular events and all-cause mortality among men and women with LDL-C <130 mg/dl, elevated hs-CRP, and concomitant evidence of moderate CKD.
Perspective: The data on efficacy of statins for primary prevention in patients with CKD are mixed. This secondary analysis of JUPITER supports use of 20 mg of rosuvastatin even in those who are at relatively low risk based upon LDL-C if the hs-CRP is >2 mg/dl. It is important to consider that the results were achieved with rosuvastatin dosing that lowered the LDL-C by 52% and hs-CRP by 37%, which are considerably greater effects than achieved with standard statin dosing. Unfortunately, a creatinine >2 mg/dl was an exclusion criterion in JUPITER, so the relative benefit in patients with more severe CKD remains unclear. Melvyn Rubenfire, M.D., F.A.C.C.

Title: Pre-Procedural Glucose Levels and the Risk for Contrast-Induced Acute Kidney Injury in Patients Undergoing Coronary Angiography
Topic: Interventional Cardiology
Date Posted: 4/23/2010
Author(s): Stolker JM, McCullough PA, Rao S, et al.
Citation: J Am Coll Cardiol 2010;55:1433-1440.
Clinical Trial: No
Related Resources
JACC Article: Pre-Procedural Glucose Levels and the Risk for Contrast-Induced Acute Kidney Injury in Patients Undergoing Coronary Angiography

Study Question: What is the relationship between hyperglycemia and risk of contrast-induced acute kidney injury (CI-AKI) in patients undergoing coronary angiography for myocardial infarction (MI)?
Methods: The authors evaluated the association between preprocedural glucose level and CI-AKI in 6,358 patients with acute MIs undergoing coronary angiography. Patients were stratified into five preprocedural glucose groups: <110 mg/dl, 110 to <140 mg/dl, 140 to <170 mg/dl, 170 to <200 mg/dl, and ≥200 mg/dl. The primary outcome was CI-AKI and was defined as a rise in serum creatinine of ≥0.3 mg/dl absolute or ≥50% relative serum creatinine increase 48 hours after the procedure.
Results: There was no relationship between preprocedural glucose and CI-AKI in patients with known prior diabetes mellitus. There was a significant association between glucose and CI-AKI risk in patients without diabetes (CI-AKI rates across the five glucose groups from lowest to highest: 8.2%, 9.9%, 12.4%, 14.9%, and 24.3%; p < 0.001). The association between CI-AKI and preprocedural glucose in nondiabetics remained significant after adjusting for differences in baseline confounders (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.00-1.71 for glucose 110 to <140 mg/dl; OR 1.51, 95% CI 1.11-2.10 for glucose 140 to <170 mg/dl; OR 1.58, 95% CI 1.03-2.43 for glucose 170 to <200 mg/dl; and OR 2.14, 95% CI 1.46-3.14 for glucose >200 mg/dl.
Conclusions: Elevated preprocedural glucose is associated with greater risk for CI-AKI in nondiabetic patients who undergo coronary angiography for acute MI.
Perspective: New-onset renal dysfunction is common in patients undergoing primary percutaneous coronary intervention, although it is not certain if contrast media is the sole mediator of the so-called CI-AKI. This study found that hyperglycemia is a risk factor for this entity in nondiabetics, but not in diabetics. This suggests that hyperglycemia is likely a marker, but not a mediator of renal dysfunction in patients undergoing angiography for acute MI. It may be reasonable to consider measures to reduce the risk of renal dysfunction in hyperglycemic patients undergoing angiography (minimizing contrast volume and ensuring adequate prehydration). Hitinder S. Gurm, M.B.B.S., F.A.C.C

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Clinical Consequences of Intense Athletic Training
New Videos from JACC Interventions
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Title: Delays in Filling Clopidogrel Prescription After Hospital Discharge and Adverse Outcomes After Drug-Eluting Stent Implantation: Implications for Transitions of Care
Topic: General Cardiology
Date Posted: 4/26/2010
Author(s): Ho PM, Tsai TT, Maddox TM, et al.
Citation: Circ Cardiovasc Qual Outcomes 2010;Apr 20:[Epub ahead of print].
Clinical Trial: No
Study Question: How do delays in filling clopidogrel prescriptions impact on outcomes after drug-eluting stent (DES) placement?
Methods: Data from three large integrated health care systems, from January 1, 2004 to December 20, 2007, were reviewed as part of the present analysis. The study population comprised patients who were discharged after DES placement. Information regarding clopidogrel prescriptions was obtained from pharmacy dispensing data. The primary endpoint of interest was all-cause mortality or myocardial infarction (MI), ascertained through April 2008.
Results: A total of 7,402 patients were included in the cohort, of which 1,210 (16%) did not fill their clopidogrel prescription on the day of discharge. The median time delay was 3 days (interquartile range, 1-23 days). Compared to patients who filled their clopidogrel prescription on the day of discharge, patients with any delay had higher rates of the primary endpoint (death or MI) during follow-up (14.2% vs. 7.9%, p < 0.001). In multivariate analysis, patients who had delays in filling clopidogrel prescriptions had an increased risk for death or MI (hazard ratio, 1.53; 95% confidence interval, 1.25-1.87). Similar risks were observed when different time delay periods were examined from greater than 1-day delay to greater than 5-day delay. Adverse outcomes occurred most frequently in the first 30 days after discharge. Additional factors associated with delay included older age, prior MI, diabetes, renal failure, prior revascularization, cardiogenic shock, in-hospital bleeding, and clopidogrel use within 24 hours of admission.
Conclusions: The authors concluded that a substantial number of patients delay filling clopidogrel prescriptions after DES implantation and that this delay is associated with increased risk for adverse outcomes including death and MI.
Perspective: These data support the need for early follow-up after discharge from the hospital. Patients who are seen shortly after discharge are more likely to adhere to cardiac medications. It is concerning that many of the factors associated with delay in clopidogrel prescriptions are also associated with increased risk for in-stent thrombosis. It would be prudent to make sure that such patients have early follow-up with their health care providers or support staff. Elizabeth A. Jackson, M.D., F.A.C.C.

Title: Transcatheter Valve-in-Valve Implantation for Failed Bioprosthetic Heart Valves
Topic: Cardiovascular Surgery
Date Posted: 4/26/2010
Author(s): Webb JG, Wood DA, Ye J, et al.
Citation: Circulation 2010;121:1848-1857.
Clinical Trial: No
Study Question: What is the role of transcatheter heart valve implantation within a failed bioprosthesis?
Methods: The investigators performed valve-in-valve implantations in 24 high-risk patients. Surgical reasons for determination of high risk included ≥2 prior thoracotomies in seven, severe pulmonary hypertension in seven, complex congenital cardiac disease in six, severe double-valve disease in five, hepatic cirrhosis in two, severe coronary disease in two, malignancy in one, and carcinoid syndrome in one patient. In addition, a subjective impression of frailty was documented by surgeons in seven elderly patients. Failed valves were aortic (n = 10), mitral (n = 7), pulmonary (n = 6), or tricuspid (n = 1) bioprostheses.
Results: The study investigators reported that implantation was successful, with immediate restoration of satisfactory valve function in all but one patient. No patient had more than mild regurgitation after implantation. No patients died during the procedure. Thirty-day mortality was 4.2%. Mortality was related primarily to learning-curve issues early in this high-risk experience. At baseline, 88% of patients were in New York Heart Association functional class III or IV; at the last follow-up, 88% of patients were in class I or II. At a median follow-up of 135 days (interquartile range, 46-254 days) and a maximum follow-up of 1,045 days, 91.7% of patients remained alive, with satisfactory valve function.
Conclusions: The authors concluded that transcatheter valve-in-valve implantation is a reproducible option for the management of bioprosthetic valve failure. Aortic, pulmonary, mitral, and tricuspid tissue valves were amenable to this approach.
Perspective: This is an important report about the utility of transcatheter valve-in-valve implantation for a failed bioprosthetic valve. Although the sample size is small, the encouraging results suggest that this approach may ultimately become the procedure of choice in valve replacement given the low perioperative risk accompanying this procedure. Large multicenter studies are needed to determine whether indeed this technique can be widely utilized. Ragavendra R. Baliga, M.B.B.S.

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Title: Reproducibility of Proximal Isovelocity Surface Area, Vena Contracta, and Regurgitant Jet Area for Assessment of Mitral Regurgitation Severity
Topic: Noninvasive Cardiology
Date Posted: 4/26/2010
Author(s): Biner S, Rafique A, Rafii F, et al.
Citation: JACC Cardiovasc Imaging 2010;3:235-243.
Clinical Trial: No
Study Question: What is the interobserver variability of different Doppler parameters of mitral regurgitation (MR) severity?
Methods: Data from 16 patients with MR were interpreted by 18 echocardiographers from 11 institutions. All echocardiograms were acquired on a standardized platform by a single experienced research sonographer and each echocardiographer evaluated the identical images for vena contracta width (VCW), effective regurgitant orifice area by proximal isovelocity surface area method (PISA), and qualitative assessment of MR jet area in the left atrium. Results were dichotomized as representing severe or nonsevere MR.
Results: The etiology of MR was degenerative in eight and functional in eight, and the MR jet was eccentric in ten and central in six. The PISA contour was spherical in ten and nonspherical in six, and the MR orifice was clearly identifiable in seven patients. There was ≥30% variation in PISA radius and VCW over the cardiac cycle in 7 of 16. Severity of MR on the basis of jet area was considered interpretable in 273 of 288 (95%) instances, in 206 of 288 (72%) for VCW, and in 72% for PISA. By jet area, MR was severe in 62% of cases and in 36% and 41% using VCW and PISA (p < 0.001). Raw agreement and Kappa coefficients for severity determination based on jet area were 75 ± 16% and 0.32. Corresponding values for VCW were 75 ± 15% and 0.28, and for PISA were 78 ± 15% and 0.37. Substantial (≥80%) raw agreement among readers, was noted for 44% of jet area measurements, 44% of VCW, and 38% of PISA measurements. Univariate predictors of suboptimal raw agreement (<80%) for jet area were degenerative etiology of MR, and for VCW, eccentric rather than central jets and an identifiable MR orifice. For PISA, predictors of suboptimal agreement were an eccentric jet, degenerative etiology, and ≥30% systolic variation in PISA radius.
Conclusions: Separation of severe from nonsevere MR by jet area, VCW, and PISA measurements is associated with substantial interobserver variability. An identifiable regurgitant orifice and stable dimensions of a regurgitant jet over the course of systole are associated with higher reproducibility.
Perspective: This study provides critically important information regarding the reproducibility of clinical assessment of MR severity by Doppler echocardiography. Current guidelines suggest a multi-modality approach to determine MR severity, including the parameters measured in this study as well as an assessment of left atrial and left ventricular size and function. In this study, 18 echocardiographers with between 2 and 40 years of experience evaluated identical images for determination of jet area, VCW, and PISA radius, all of which are common clinically employed parameters for determination of MR severity. The authors noted a disturbing lack of agreement among experienced observers for separation of severe from nonsevere MR based on traditional criteria of an effective regurgitant orifice >40 mm2, grade 3-4 visually assessed MR, or VCW ≥7 mm. This significant variability could be tracked to a degenerative etiology in which jets are frequently eccentric, the vena contracta may not be circular, and the PISA contour may not be truly hemispherical and/or varies in diameter over the course of systole. A minor limitation to this study, which can be expected in clinical practice as well, was the lack of standardization with respect to precisely where in the cardiac cycle PISA radius should be measured (average diameter, minimum diameter, maximum diameter, etc.) and similar lack of standardization for VCW. While a technical limitation in study design, the manner in which these echocardiograms were analyzed faithfully reproduces clinical practice. This study should provide a cautionary tale to the analyzing echocardiographer as well as the physician utilizing the information, and drives home the point that assessment of MR severity must be based on analyzing the entire spectrum of available data and certainly not based on a single “quantifiable” variable alone. William F. Armstrong, M.D., F.A.C.C.

Title: A Phase II, Randomized, Double-Blind, Multicenter, Based on Standard Therapy, Placebo-Controlled Study of the Efficacy and Safety of Recombinant Human Neuregulin-1 in Patients With Chronic Heart Failure
Topic: Heart Failure/Transplant
Date Posted: 4/26/2010 5:00:00 PM
Author(s): Gao R, Zhang J, Cheng L, et al.
Citation: J Am Coll Cardiol 2010;55:1907-1914.
Clinical Trial: yes
Related Resources
JACC Article: A Phase II, Randomized, Double-Blind, Multicenter, Based on Standard Therapy, Placebo-Controlled Study of the Efficacy and Safety of Recombinant Human Neuregulin-1 in Patients With Chronic Heart Failure

Study Question: What is the effect of recombinant human neuregulin-1 (rhNRG-1) on left ventricular (LV) function and symptoms in patients with chronic heart failure (CHF)?
Methods: Forty-four CHF patients designated as New York Heart Association functional class II or III were enrolled in a double-blind, randomized manner and treated with a placebo or rhNRG-1 (0.3, 0.6, or 1.2 μg/kg/day) for 10 days, in addition to standard therapies. The follow-up period was 90 days; LV function and structure measured by magnetic resonance imaging were the primary endpoints.
Results: Although not statistically different from placebo, the LV ejection fraction (LVEF)% was significantly increased by 27.11 ± 31.12% (p = 0.009) at day 30 after rhNRG-1 treatment in the 0.6-μg/kg group, whereas it was only increased 5.83 ± 25.75% in the placebo group (p = 0.49). In addition, there were decreases in end-systolic volume (ESV) (-11.58 ± 12.74%, p = 0.002) and EDV (-5.64 ± 10.03%, p = 0.05) in the 0.6-μg/kg/day group at day 30; more importantly, both ESV and end-diastolic volume (EDV) levels continued to decrease at day 90 (-20.79 ± 17.03% and -14.03 ± 13.17%, respectively), accompanied by a sustained increase in LVEF%. This suggests that short-term treatment with rhNRG-1 results in a long-term reversal of remodeling. The effective dose was proven to be tolerable and safe for CHF patients.
Conclusions: The authors concluded that rhNRG-1 improved the cardiac function of CHF patients by increasing the LVEF% and affected remodeling by decreasing ESV and EDV compared with pretreatment.
Perspective: Neuregulin-1 is expressed in the myocardium and appears to play an important role in the functional and structural integrity of the heart. Preclinical studies have demonstrated that injection of NRG-1 into adult mice leads to cardiomyocyte proliferation and promotes myocardial regeneration after myocardial infarction. Although the etiology of myocardial dysfunction in the current clinical study is not clear, one of the rhNRG-1 dose regimens may have provided beneficial effects on contractile function in patients with CHF. There was no beneficial effect of treatment on symptoms and results were not statistically different compared to the placebo group. The possible benefits of drug treatment were not observed in the high-dose group where adverse events were also most common. Additional clinical studies are needed to confirm a potential beneficial effect of this treatment. Daniel T. Eitzman, M.D., F.A.C.C.

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Title: Prognostic Value of 64-Slice Cardiac Computed Tomography: Severity of Coronary Artery Disease, Coronary Atherosclerosis, and Left Ventricular Ejection Fraction
Topic: Noninvasive Cardiology
Date Posted: 4/27/2010
Author(s): Chow BJ, Wells GA, Chen L, et al.
Citation: J Am Coll Cardiol 2010;55:1017-1028.
Clinical Trial: No
Related Resources
JACC Article: Prognostic Value of 64-Slice Cardiac Computed Tomography: Severity of Coronary Artery Disease, Coronary Atherosclerosis, and Left Ventricular Ejection Fraction

Study Question: What are the relative prognostic implications of findings on 64-slice cardiac computed angiography (CTA) compared to traditional risk factor assessment?
Methods: CTA was performed on 2,076 patients who were followed for a mean of 16 ± 8 months. CTA was analyzed for left ventricular ejection fraction (LVEF) and the CTA coronary arteriogram was evaluated on a 17-segment model. Coronary stenoses were defined as absent, <50%, 50-69%, or ≥70%. Patients were categorized as having nocoronary artery disease (CAD), nonobstructive CAD, or obstructive CAD. A total plaque score (TPS) was calculated as the number of segments involved with atherosclerotic plaque. Clinical predictors included nature of symptoms, age, and presence of hypertension and diabetes, among other variables. Patients were followed for major adverse cardiac events (MACE) of nonfatal myocardial infarction and cardiac death.
Results: Average subject age was 58 ± 11.7 years and 52% were male. The average pretest likelihood for CAD was 33.4 ± 34.3%. Nonanginal chest pain was present in 28%, atypical angina in 14.5%, and typical angina in 15.7%, and 42% had no chest pain. On CTA, LVEF was 64.2 ± 10.5%. Normal coronary arteries were noted in 591 (28.5%), nonobstructive CAD in 866 (41.7%), obstructive CAD ≥50% in 619 (29.8%), and CAD ≥70% in 427 (20.6%). High-risk CAD was present in 97 (4.7%), MACE occurred in one subject without CAD, in seven (0.8%) with nonobstructive CAD, in 19 (3.6%) with nonhigh-risk obstructive CAD, and in four (4.1%) with high-risk obstructive CAD. Overall, MACE was noted in 0.2%, 0.8%, 1.6%, 5.3%, and 7.0% of patients without CAD, with nonobstructive CAD, and with one-, two-, and three-vessel CAD (≥50%). Cox models of clinical and CTA variables revealed a global chi-square of 24.97 for clinical variables, which increased to 43.81 with the addition of CAD variables and 54.48 with subsequent addition of LVEF (for both p ≤ 0.001). A similar incremental yield for event prediction was noted for all-cause mortality and nonfatal myocardial infarction, with the sequential addition of CAD variables, LVEF, and TPS.
Conclusions: CTA variables of coronary stenosis severity, LVEF, and TPS have prognostic value in patients presenting for CTA and incremental value over routine clinical predictors.
Perspective: Multiple studies have demonstrated the diagnostic accuracy of CTA for identifying and quantifying CAD as well as calculation of LVEF. This study evaluated a large population of patients followed for an average of <2 years, and demonstrates the incremental value of CTA parameters of CAD presence and overall severity as well as LVEF to standard clinical variables for prediction of events. A significant limitation of this study is the relatively low number of events (31 patients with cardiac death or nonfatal myocardial infarction) and a large number of patients (n = 243) who underwent revascularization procedures. Data regarding indication for revascularization were not provided. Multiple studies have previously demonstrated a link between outcomes and LVEF as well as between coronary disease severity and outcome. The relative role of an anatomical assessment by CTA compared to functional assessment by stress testing remains uncertain. It is not unreasonable to incorporate results of CTA into clinical decision making. William F. Armstrong, M.D., F.A.C.C.

Title: Clinical Features and Outcome of Hypertrophic Cardiomyopathy Associated With Triple Sarcomere Protein Gene Mutations
Topic: Heart Failure/Transplant
Date Posted: 4/27/2010
Author(s): Girolami F, Ho CY, Semsarian C, et al.
Citation: J Am Coll Cardiol 2010;55:1444-1453.
Clinical Trial: No
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JACC Article: Clinical Features and Outcome of Hypertrophic Cardiomyopathy Associated With Triple Sarcomere Protein Gene Mutations

Study Question: What is the clinical profile associated with triple sarcomere gene mutations in hypertrophic cardiomyopathy (HCM)?
Methods: The study cohort was comprised of 488 unrelated index HCM patients. These patients underwent screening for myofilament gene mutations by direct deoxyribonucleic acid sequencing of eight genes, including myosin binding protein C (*MYBPC3*), beta-myosin heavy chain (*MYH7)*, regulatory and essential light chains (MYL2, MYL3), troponin-T (TNNT2), troponin-I (*TNNI3*), alphatropomyosin (TPM1), and actin (ACTC).
Results: The investigators found that of the 488 index patients, four (0.8%) harbored triple mutations, as follows: *MYH7-*R869H, *MYBPC3-*E258K, and *TNNI3-*A86fs in a 32-year-old woman; *MYH7-*R723C, *MYH7-*E1455X, and *MYBPC3-*E165D in a 46-year-old man; *MYH7-*R869H, *MYBPC3*-K1065fs, and *MYBPC3-*P371R in a 45-year-old woman; and *MYH7*-R1079Q, *MYBPC3-*Q969X, and *MYBPC3-*R668H in a 50-year-old woman. One had a history of resuscitated cardiac arrest, and three had significant risk factors for sudden cardiac death, prompting the insertion of an implantable cardioverter defibrillator in all, with appropriate shocks in two patients. Moreover, three of four patients had a severe phenotype with progression to end-stage HCM by the fourth decade, requiring cardiac transplantation (n = 1) or biventricular pacing (n = 2). The fourth patient, however, had clinically mild disease.
Conclusions: The authors concluded that hypertrophic cardiomyopathy caused by triple sarcomere gene mutations was rare, but conferred a remarkably increased risk of end-stage progression and ventricular arrhythmias, supporting an association between multiple sarcomere defects and adverse outcome.
Perspective: This study has two important messages. The first is that triple sarcomere mutations are associated with adverse outcome, and the second is that these mutations are rare. More data are needed to determine whether early identification of triple sarcomere mutations by routine testing of HCM patients is a cost-effective strategy in the risk-stratification of these patients. Ragavendra R. Baliga, M.B.B.S.