You don't need to be signed in to read BMJ Blogs, but you can register here to receive updates about other BMJ products and services via our site.

Transcatheter aortic valve implantation – are we moving from equivalent to preferred in high-risk surgical patients?

23 Jul, 14 | by Alistair Lindsay

Transcatheter aortic valve implantation (TAVI) has expanded the options for the treatment of severe aortic stenosis, particularly in patients for whom the surgical risk of valve replacement is felt to be prohibitive.  Prior studies have demonstrated TAVI reduces mortality relative to medical management among patients unable to undergo valve surgery.  Among patients considered to be at high surgical risk, TAVI has been shown to have similar 1-year survival compared to surgery, but associated with a higher rate of stroke.  In this study of the CoreValve self-expanding transcatheter bioprosthethic valve, patients deemed to be at high surgical risk (estimated risk of death ≥ 15% within 30 days of surgery) were randomized in a 1:1 fashion to either TAVI or surgical valve replacement.  The primary end-point was mortality at 1 year.  A total of 795 patients were randomized at 45 experienced US centers.  Although the trial was powered for non-inferiority, TAVI demonstrated an absolute 1-year mortality reduction of 4.9% (14.2% vs. 19.1%) demonstrating not only non-inferiority (P<0.001), but actual superiority (P=0.04).  In additional analyses, paravalvular leak was more common in TAVI patients, while quality of life indices and rates of stroke were similar in TAVI and surgical patients.

Conclusions

In this study of the CoreValve bioprosthesis, 1-year survival was greater among patients with severe aortic stenosis and high operative risk treated with TAVI in comparison to conventional surgical valve replacement.  We now await studies evaluating the outcome of TAVI in lower risk patients with severe aortic stenosis.

Summarized by Steven M. Bradley and Hussain Contractor

  • Adams DH, Popma JJ, Reardon MJ, Yakubov SJ, Coselli JS, Deeb GM, Gleason TG, Buchbinder M, Hermiller J Jr, Kleiman NS, Chetcuti S, Heiser J, Merhi W, Zorn G, Tadros P, Robinson N, Petrossian G, Hughes GC, Harrison JK, Conte J, Maini B, Mumtaz M, Chenoweth S and Oh JK. Transcatheter aortic-valve replacement with a self-expanding prosthesis. N Engl J Med. 2014 May 8;370(19):1790-8.

Cryptogenic stroke due to undetected atrial fibrillation – longer ECG monitoring may be the key

23 Jul, 14 | by Alistair Lindsay

Up to 40% of ischemic strokes remain unexplained after routine evaluation and thus are considered cryptogenic. However, a number of these strokes may be due to an undetected episode of paroxysmal atrial fibrillation (AF) where anticoagulation can reduce the risk of subsequent ischemic stokes. Although a minimum of 24 hours of ECG monitoring is guideline recommended in the evaluation of ischemic stroke to identify AF, the optimal duration of monitoring remains undetermined. Among patients with cryptogenic stroke, two concurrent publications evaluated the AF diagnostic yield of extended ECG monitoring.

In the first study, 572 patients with a history of cryptogenic stroke or transient ischemic attack in the prior 6 months were randomized to 30-day event triggered ECG monitoring or 24-hour ECG monitoring. Among patients with 30-day monitoring, an episode of AF lasting at least 30 seconds was identified in 16.1% of patients compared with 3.2% in 24-hour monitoring (absolute difference, 12.9 percentage points; 95% confidence interval [CI], 8.0 to 17.6; P<0.001; number needed to screen, 8). In the second study, 441 patients with cryptogenic stroke and 24 hours of ECG monitoring as part of the initial work-up were randomized to additional monitoring with an implantable loop recorder device with an AF detection algorithm or conventional follow-up during which any further monitoring was decided by local policy. The trial’s primary end-point was the time to first detection of AF (at least 30 seconds in duration).   At 6 months there was a marked difference in AF detection between groups with AF detected in 8.9% of patients monitored with an implantable loop recorder versus 1.4% of the control group (HR, 6.4; 95% CI, 1.9 to 21.7; P<0.001). By 12 months this difference in AF detection had increased to 12.4% in monitored patients versus 2.0% in controls (HR 7.3, 95% CI 2.6 to 20.8; P<0.001). The preponderance of detected AF episodes were asymptomatic in this trial.

Conclusions

In the evaluation of patients with cryptogenic stroke, prolonged ECG monitoring resulted in markedly increased rates of AF detection. Future studies are needed to both identify patient populations most likely to benefit from prolonged ECG monitoring and the outcome implications of improved AF detection in cryptogenic stroke.

Summarized by Steven M. Bradley and Hussain Contractor

  • Gladstone DJ, Spring M, Dorian P, Panzov V, Thorpe KE, Hall J, Vaid H, O’Donnell M, Laupacis A, Côté R, Sharma M, Blakely JA, Shuaib A, Hachinski V, Coutts SB, Sahlas DJ, Teal P, Yip S, Spence JD, Buck B, Verreault S, Casaubon LK, Penn A, Selchen D, Jin A, Howse D, Mehdiratta M, Boyle K, Aviv R, Kapral MK, Mamdani M; EMBRACE Investigators and Coordinators. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014 Jun 26;370(26):2467-77

Opinion based guideline recommendations less likely to stand the test of time

29 Jun, 14 | by Alistair Lindsay

Limited data exists on how frequently guidelines change over time. This study examined how frequently class I recommendations (“procedure/treatment should be performed/administered”) in ACC/AHA guidelines were downgraded to a lower class over time. Four independent reviewers examined 619 class I ACC/AHA recommendations in 11 guidelines released between 1998-2007 and revised between 2006-2013. Overall, 495 recommendations (80.0%; 95% CI 76.6% – 83.1%) were retained in subsequent versions, 57 (9.2%; 95% 7.0% – 11.8%) were downgraded or reversed, and 67 (10.8%; 95% CI 8.4% – 13.3%) were omitted. Compared to recommendations based on multiple randomized trials, the probability of a guideline recommendation being omitted, reversed or downgraded was higher for recommendations based on opinion (OR 3.14; 95% CI 1.69-5.85) or on 1 trial or observational data (OR 3.49; 95% CI 1.45-8.40).

Conclusion: 1 in 5 class I guideline recommendations are omitted, reversed, or downgraded over time.  These changes in guidelines are far more common for recommendations based on little to no randomized trial data.  These findings question the wisdom of class I indications in the absence of solid evidence to support the recommendation.

 Summarized by Supriya Shore and Steven M. Bradley

  • Neuman MD, Goldstein JN, Cirullo MA, Schwartz JS. Durability of class I American College of Cardiology/American Heart Association clinical practice guideline recommendations. JAMA. May 28 2014;311(20):2092-2100.

Differences in Statin Eligible Patients across Guidelines

29 Jun, 14 | by Alistair Lindsay

Recent ACC/AHA guidelines recommend consideration of statin therapy among patients with a 7.5% 10-year risk of atherosclerotic cardiovascular disease (CVD).  In this study, the authors examined implications of these new guidelines as compared with previous European Society of Cardiology (ESC) and Adult Treatment Panel III (ATP III) guidelines in a Dutch population-based prospective cohort of 4,854 healthy participants over 55 years of age. In this cohort,  96.4% men and 65.8% women would be recommended statinsunder the new ACC/AHA guidelines. In contrast, 66.1% of men and 39.1% of women would be recommended statins under ESC guidelines and 52.0% of men and 35.5% of women would be recommended statins by ATP III guidelines.  Subgroup analyses demonstrated under ACC/AHA guidelines nearly all women age 65 or older would be recommended statin therapy.

Conclusion: Application of the new ACC/AHA CVD prevention guidelines to a Dutch cohort found that nearly all men age 55 or older and women age 65 or older were candidates for statin therapy.  This was a dramatic increase in statin eligible patients relative to prior ESC and ATP III guidelines. Given the near uniform statin recommendation at these age cutoffs, these findings raise questions as to the utility of the new ACC/AHA CVD risk prediction model in guiding treatment decisions.

 Summarized by Supriya Shore and Steven M. Bradley

  • Kavousi M, Leening MJ, Nanchen D, et al. Comparison of application of the ACC/AHA guidelines, Adult Treatment Panel III guidelines, and European Society of Cardiology guidelines for cardiovascular disease prevention in a European cohort. JAMA. 2014;311(14):1416-1423.

Validation of the Pooled Cohort Risk Equations from Recent ACC/AHA Guidelines

29 Jun, 14 | by Alistair Lindsay

Recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the assessment of cardiovascular risk recommend a new 10-year atherosclerotic cardiovascular disease (CVD) risk prediction tool called the Pooled Cohort risk equation. This new predictive model developed from cohorts of patients that were largely studied prior to the year 2000.  In light of the declining CVD incidence since 2000, the external validity of the Pooled Cohort risk equation has been questioned.  The present study sought to validate the Pooled Cohort equation in a contemporary cohort of 10,997 individuals aged 45-79 years without a prior history of atherosclerotic CVD for whom the guidelines would recommend consideration of a statin.  In 47,481 person-years of follow-up, 192 coronary heart disease events and 146 strokes were observed. Differences in observed and predicted risk were small in patients for whom a statin should be considered, consistent with good model calibration.  Further, the C-index was 0.72 (95% CI 0.70 – 0.75) consistent with moderate discrimination.

Conclusion: The recently published Pooled Cohort risk equations recommended by ACC/AHA guidelines demonstrated good calibration and discrimination among individuals who should be considered for statin therapy.  These findings support the validity of the model among patients being considered for statin therapy.

 Summarized by Supriya Shore and Steven M. Bradley

  • Muntner P, Colantonio LD, Cushman M, et al. Validation of the atherosclerotic cardiovascular disease Pooled Cohort risk equations. JAMA. 2014;311(14):1406-1415.

Clonidine and Aspirin Fail to Reduce Peri-operative Myocardial Infarction

29 Jun, 14 | by Alistair Lindsay

Myocardial infarction (MI) is the most common major vascular event that occurs after planned non-cardiac surgery.  Multiple strategies have been assessed to try and reduce the rates of peri-operative MI, but few have consistently demonstrated substantial benefit.  With a pro-thrombotic environment and marked sympathetic activation thought to play etiological roles, in the POISE-2 study, the antiplatelet agent aspirin and the alpha-agonist clonidine, were studied in a 2×2 factorial design.   A total of 10,010 patients were randomized in this multi-center, international study to receive a combination of aspirin and clonidine or corresponding placebo.  The trial results from both arms were reported separately, but both arms of the study were neutral for the primary composite outcome of death or nonfatal myocardial infarction at 30 days. The 30-day event rate was 7.0% in patients treated with aspirin and 7.1% in the placebo group (HR, 0.99; 95% CI, 0.86 to 1.15; P=0.92).   Among patients treated with clonidine, 6.6% suffered an event at 30-days compared with 5.9% in the placebo group (HR, 1.11; 95% CI, 0.95 to 1.30; P=0.18).  Aspirin significantly raised the risk of major bleeding (P=0.04) and clonidine increased the risk of clinically significant hypotension (P<0.001).

Conclusion: This large randomized study of aspirin and clonidine in patients undergoing non-cardiac surgery failed to demonstrate benefit from either intervention in comparison to placebo.  Furthermore, both drugs demonstrated evidence of potentially significant side-effects. The need to further define effective agents to reduce peri-operative myocardial infarction risk remains.

Summarized by Steven M. Bradley and Hussain Contractor

  • Devereaux PJ, Mrkobrada M, Sessler DI, Leslie K, Alonso-Coello P, Kurz A, Villar JC, Sigamani A, Biccard BM, Meyhoff CS, Parlow JL, Guyatt G, Robinson A, Garg AX, Rodseth RN, Botto F, Lurati Buse G, Xavier D, Chan MT, Tiboni M, Cook D, Kumar PA, Forget P, Malaga G, Fleischmann E, Amir M, Eikelboom J, Mizera R, Torres D, Wang CY, VanHelder T, Paniagua P, Berwanger O, Srinathan S, Graham M, Pasin L, Le Manach Y, Gao P, Pogue J, Whitlock R, Lamy A, Kearon C, Baigent C, Chow C, Pettit S, Chrolavicius S and Yusuf S. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014 Apr 17;370(16):1494-503.
  •  Devereaux PJ, Sessler DI, Leslie K, Kurz A, Mrkobrada M, Alonso-Coello P, Villar JC, Sigamani A, Biccard BM, Meyhoff CS, Parlow JL, Guyatt G, Robinson A, Garg AX, Rodseth RN, Botto F, Lurati Buse G, Xavier D, Chan MT, Tiboni M, Cook D, Kumar PA, Forget P, Malaga G, Fleischmann E, Amir M, Eikelboom J, Mizera R, Torres D, Wang CY, Vanhelder T, Paniagua P, Berwanger O, Srinathan S, Graham M, Pasin L, Le Manach Y, Gao P, Pogue J, Whitlock R, Lamy A, Kearon C, Chow C, Pettit S, Chrolavicius S, Yusuf S. Clonidine in patients undergoing noncardiac surgery. N Engl J Med. 2014 Apr 17;370(16):1504-13.

clonidineVSaspirin

Figure: Kaplain-Meier curves for clonidine and aspirin administered in the peri-operative period failed to demonstrate any benefit in reducing myocardial events in comparison with placebo

Vegetarian diet associated with lower blood pressure  

29 Jun, 14 | by Alistair Lindsay

Conflicting evidence exists on the association between a vegetarian diet (involving no or rare meat consumption) and hypertension. In this meta-analysis, the authors included 7 controlled trials and 32 observational studies examining the association between vegetarian diets and hypertension. The 7 trials included 311 individuals with a mean age of 44.5 years.  After pooling of trial results, a vegetarian diet was associated with a mean reduction in systolic blood pressure (SBP) by 4.8mmHg (95% CI 3.1 to 6.6 mmHg reduction; P<.001) and diastolic blood pressure (DBP) by 2.2 mmHg (95% CI 1.0 to 3.5 mmHg reduction; P<.001). The 32 observational studies included 21,604 individuals with a mean age of 46.6 years.  After pooling results of these observational studies, a vegetarian diet was associated with lower SBP by 6.9 mmHg (95% CI 4.7 to 9.1 mmHg lower; P<.001) and lower DBP by 4.7 mmHg (95% CI 3.1 to 6.3 mmHg lower; P<.001). Meta-regression suggested that the association between vegetarian diet and BP was stronger amongst men and those with higher baseline BP.

Conclusion: In this meta-analysis, a vegetarian diet was associated with lower blood pressure compared to omnivorous diet. However, observational studies used for the meta-analysis were all cross-sectional with significant heterogeneity in the patient populations. Additionally, adjustment for other lifestyle factors associated with a vegetarian diet and food composition could not be performed in this analysis.

 Summarized by Steven M. Bradley and Supriya Shore

  •  Yokoyama Y, Nishimura K, Barnard ND, et al. Vegetarian diets and blood pressure: a meta-analysis. JAMA internal medicine. Apr 2014;174(4):577-587.

ACEI reduce mortality whereas ARB did not in diabetic populations  

29 Jun, 14 | by Alistair Lindsay

Where the benefits of renin-angiotensin-aldosterone system blockade for reduction of cardiovascular risk are similar for ACE inhibitors (ACEI) and ARBs are unknown.  The answer to this question is of particular importance among diabetics, given the higher cardiovascular risk in this patient population.  In this meta-analysis, the authors examined effect of ACEI and ARBs on the incidence of mortality and cardiovascular events in diabetics. A total of 23 randomized trials comparing ACEI to placebo/no treatment/ other medications and 13 trials comparing ARBS to placebo/other medications were included. Trials with ACEI enrolled more patients with coronary artery disease than trials of ARBs. Pooled results showed that ACEI reduced the risk of all-cause mortality (relative risk [RR] 0.87; 95% CI 0.78 – 0.98) and cardiovascular events (RR 0.83; 95% CI 0.70 – 0.99). Treatment with ARBs did not influence all-cause mortality (RR 0.94; 95% CI 0.82 – 1.08) or cardiac mortality (RR 0.94; 95% CI 0.85 – 1.01). Meta-regression found the observed effects of ACEI on mortality did not differ by patient baseline characteristics or by ACEI agent.

 Conclusion: This meta-analysis found that ACEI reduced rates of all cause and cardiovascular mortality, while ARB did not.  These findings suggest that ACEI should be considered as first line therapies in diabetics.

 Summarized by Steven M. Bradley and Supriya Shore

  •  Cheng J, Zhang W, Zhang X, et al. Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on All-Cause Mortality, Cardiovascular Deaths, and Cardiovascular Events in Patients With Diabetes Mellitus: A Meta-analysis. JAMA internal medicine. May 1 2014;174(5):773-785.

Epinephrine for Non-Shockable In-hospital Cardiac Arrest — Time is of the Essence

29 Jun, 14 | by Alistair Lindsay

Guidelines recommend epinephrine as the primary medical intervention for cardiac arrest. However, no randomized trial data are available to support this recommendation. In this observational study from the American Heart Association’s Get With The Guidelines – Resuscitation multi-center registry of in-hospital cardiac arrest, the authors sought to determine if timing of epinephrine administration in the setting of non-shockable (i.e. pulseless electrical activity or asystole) in-hospital cardiac arrest is associated with patient outcomes. Among 25,095 patients with non-shockable in-hospital cardiac arrest, the median time to first epinephrine was 3 minutes (IQR 1-5 minutes). When analyzed at 3 minute intervals, there was a stepwise decrease in survival to discharge with increasing time to epinephrine. As compared to 1-3 minutes, the adjusted odds ratios were 0.91 (95% confidence interval [CI] 0.82 – 1.00; p = 0.055) for 4-6 minutes, 0.74 (95% CI 0.63 – 0.88; p < 0.001) for 7-9 minutes, and 0.63 (95% CI 0.52 – 0.76) for > 9 minutes. The authors also performed sensitivity analyses to ensure the primary analysis was not confounded by overall delays in initiation of resuscitation independent of time to epinephrine, by the selection of 3 minute increments for categorization of epinephrine administration, or by missing covariates. The results of the sensitivity analyses were similar to those of the primary analysis.

Conclusion: In this large observational study, increased time to epinephrine for cardiac arrest with non-shockable rhythm was associated with worse patient outcomes. It is important to consider that duration of resuscitation is an important contributor to patient outcomes, and thus later administration of epinephrine may reflect longer resuscitation events with lower likelihood of survival. However, this study reiterates the need for further investigation of epinephrine for cardiac arrest to define its optimal use to improve patient survival.

Summarized by Steven M. Bradley and Preston M. Schneider

Donnino MW, Salciccioli JD, Howell MD, Cocchi MN, Giberson B, Berg K, Gautam S, Callaway C. Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry. BMJ. 2014;348.

Figure. Survival to discharge by timing of epinephrine administration among patients with non-shockable in-hospital cardiac arrest.

epinephrine4nonshockable

 

Spironolactone for heart failure with preserved ejection fraction

8 Jun, 14 | by Alistair Lindsay

Nearly half of all patients presenting with heart failure have normal or near normal left ventricular systolic function.  Optimal treatment strategies for this large patient group remain unclear.  Small mechanistic studies have suggested diastolic function may be improved by mineralocorticoid-receptor antagonists.  Whether this mechanistic benefit translates into better patient outcomes is not known.  In the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, 3445 patients with heart failure and an ejection fraction of 45% or more were randomised in a double-blind fashion to either spironolactone (15 to 45 mg daily) or placebo.  The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure with patients.  Over a mean follow-up period of 3.3 years, the primary outcome occurred in 18.6% of the spironolactone group and 20.4% of the placebo group (HR, 0.89; 95% CI, 0.77 to 1.04; P=0.14).  Compared with placebo, spironolactone resulted in a statistically significant reduction in hospitalizations for heart failure (206 patients vs. 245 patients, HR, 0.83; 95% CI, 0.69 to 0.99, P=0.04).  Use of spironolactone came at a cost of increased rates of hyperkaliemia (18.7%, vs. 9.1%), but no differences in serious adverse events.

Conclusions

In this large randomised controlled trial of patients with heart failure and preserved systolic function, the mineralocorticoid receptor antagonist spironolactone failed to result in patient benefit aside from a reduction in heart failure hospitalizations.  Whether the reduction in hospitalizations with spironolactone represents a mechanistic benefit, or just better volume control achieved through diuresis, is unclear.  Therapies that clearly improve outcomes in patients with heart failure and preserved ejection fraction remain elusive.

  • Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, Clausell N, Desai AS, Diaz R, Fleg JL, Gordeev I, Harty B, Heitner JF, Kenwood CT, Lewis EF, O’Meara E, Probstfield JL, Shaburishvili T, Shah SJ, Solomon SD, Sweitzer NK, Yang S and McKinlay SM; TOPCAT Investigators. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014 Apr 10;370(15):1383-92.

Summarized by Steven M. Bradley and Hussain Contractor

 

 

Latest from Heart

Latest from Heart

Cardiology Masterclasses

Cardiology Masterclasses