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

Repair versus replacement for ischemic mitral regurgitation

13 Apr, 14 | by Alistair Lindsay

Ischemic mitral regurgitation (MR) following myocardial infarction is common and presages a doubling in mortality for those with at least mild regurgitation.  The disorder reflects disease of the myocardium, rather than an abnormality of the valve itself. Surgical practice guidelines support intervention for severe symptomatic ischemic MR, but evidence is lacking to inform whether valvular repair or replacement is the superior surgical approach. 

In this multicenter study, a total of 251 patients with severe ischemic MR were randomized to either mitral valve repair or chordal sparing replacement with concomitant revascularization as required.  The primary end-point was the left ventricular end-systolic volume index (LVESVI) at 12 months, a parameter which is closely associated with long term outcomes. At 12 months, there was no significant difference in LVESI between patients treated with repair (54.6±25.0 mL per square meter) and replacement (60.7±31.5 mL per square meter).  There was also no difference in mortality (14.3% vs. 17.6%, hazard ratio 0.79; 95% confidence interval, 0.42 to 1.47; P=0.45), major adverse cardiovascular event rates or quality of life indices between the two groups.  A significantly higher rate of recurrence of moderate or severe MR was observed among patients treated with repair (32.6% vs. 2.3%, P<0.001).

Conclusions

In the consideration of repair versus replacement for ischemic MR, there has long been a presumed trade-off of lower surgical complication rates with repair balanced against the greater durability of valve replacement.  The present study suggests the improved durability of valve replacement may significantly outweigh any potential short-term benefit of repair.  Further long-term data on outcomes is awaited.

Summarized by Steven M. Bradley and Hussain Contractor

  • Acker MA, Parides MK, Perrault LP, Moskowitz AJ, Gelijns AC, Voisine P, Smith PK, Hung JW, Blackstone EH, Puskas JD, Argenziano M, Gammie JS, Mack M, Ascheim DD, Bagiella E, Moquete EG, Ferguson TB, Horvath KA, Geller NL, Miller MA, Woo YJ, D’Alessandro DA, Ailawadi G, Dagenais F, Gardner TJ, O’Gara PT, Michler RE, Kron IL. Mitral-valve repair versus replacement for severe ischemic mitral regurgitation. N Engl J Med. 2014 Jan 2;370(1):23-32.

 

Testosterone replacement associated with higher risk for adverse cardiovascular events

2 Feb, 14 | by Alistair Lindsay

Despite limited data on cardiovascular safety, rates of testosterone therapy are increasing dramatically. In a retrospective cohort study of 8,709 male Veterans with a low testosterone level, the authors sought to determine the association between use of testosterone therapy following coronary angiography and patient outcomes of all-cause mortality, myocardial infarction and stroke.

Patients initiated on testosterone therapy were younger and had a lower prevalence of co-morbidities. At 3 years after coronary angiography, the cumulative percentage of events from Kaplan-Meier estimates were 19.9% in untreated patients vs 25.7% in patients treated with testosterone. In propensity matched analyses with testosterone therapy modeled as a time-varying covariates, the risk of adverse outcomes was higher among testosterone treated patients (hazard ratio, 1.29; 95% CI, 1.04 to 1.58). The risk for adverse events did not vary by type of testosterone preparation used or the presence of coronary artery disease.

Conclusion:

In this observational study, use of testosterone therapy was associated with increased risk for adverse events. However, the impact of this study is limited by its observational design and study population that was limited to Veterans who underwent coronary angiography. Additional randomized studies are needed to better characterize the potential risks of testosterone therapy.

Summarized by Catherine Otto and Supriya Shore

  • Vigen R, O’Donnell CI, Baron AE, Grunwald GK, Maddox TM, Bradley SM, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA : the journal of the American Medical Association 2013;310(17):1829-36.

No Benefit from Extended Dual Anti-Platelet Therapy?

2 Feb, 14 | by Alistair Lindsay

The PARIS (patterns of non-adherence to anti-platelet regimens in stented patients) registry is a prospective observational study of patients from the US and Europe who were discharged on dual anti-platelet therapy (DAPT) following coronary stenting. Among 5018 patients from this registry, the rates of physician recommended discontinuation, brief interruption (i.e. for surgery), or disruption (ie non-compliance, bleeding) of DAPT was assessed over 2 years. The observed rate of discontinuation was 40.8%, interruption 10.5,%, and the rate of DAPT disruption was 14.4%. Patients with DAPT disruption were at significantly increased risk for major cardiovascular events compared with patients on DAPT (hazard ratio 1.50, 95% CI 1.14 – 1.97), with highest risk in the first 7 days of disruption (hazard ratio 7.04, 95% CI 3.31 – 14.95). In contrast, there was a lower risk for major adverse cardiovascular events among patients who had DAPT discontinued in comparison to patients who remained on DAPT (hazard ratio 0.63, 95% CI 0.46 – 0.86).

Conclusions:

This study suggests there is no clinical benefit to an extended duration of DAPT following PCI. However, the study cannot eliminate potential treatment bias resulting from discontinuation of DAPT in the lowest risk patients. Randomized trial data are still needed to inform best practices.

Summarized by Steven M. Bradley and Preston M. Schneider

  • Mehran R, Baber U, Steg PG, et al. Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study. The Lancet. 23;382(9906):1714–1722. doi:10.1016/S0140-6736(13)61720-1.

Weight reduction results in atrial fibrillation symptom improvement

2 Feb, 14 | by Alistair Lindsay

Obesity is known risk factor for atrial fibrillation (AF). However, the effect of weight reduction on AF symptom burden is unknown. In this study, 150 patients with symptomatic AF who were overweight or obese were randomized to a physician led weight loss program (intervention arm) or self-directed general lifestyle measures (control arm). All patients received intensive cardiometabolic risk factor management and were evaluated at 3 monthly intervals by blinded study personnel. Primary outcomes of interest were AF symptom burden and symptom severity evaluated using a validated tool to assess disease specific patient-reported health status. Secondary outcomes included holter-derived episodes of AF, left ventricular thickness and left atrial size on echocardiograms.

Over a mean follow-up duration of 15 months, a significantly larger reduction in weight was noted in the intervention arm (14.3 kg vs 3.6 kg, p<.001). Both AF symptom burden and severity scores declined more in the intervention arm compared to the control arm. Furthermore, the probability of having 1 or more AF episodes in follow-up was lower in the intervention group (0.6 [95% CI 0.5-0.7] to 0.2 [95% CI 0.1-0.3]) compared to control group (0.6 [95% CI 0.5-0.7] to 0.5 [95% CI 0.4-0.6]). While loss to follow-up rate was high (44% in intervention and 48% in control arms), they were similar in both groups and sensitivity analyses accounting for this suggested that the primary findings were robust

Conclusions:

Overall burden and severity of disease specific AF symptoms was reduced with a structured, intensive weight loss program. This appeared to correlate with measures of AF frequency and duration. The myriad benefits of weight loss now include management of AF.

Summarized by Steven M. Bradley and Supriya Shore

  • Abed HS, Wittert GA, Leong DP, Shirazi MG, Bahrami B, Middeldorp ME, et al. Effect of weight reduction and cardiometabolic risk factor management on symptom burden and severity in patients with atrial fibrillation: a randomized clinical trial. JAMA 2013;310(19):2050-60.

Target cooling temperatures in cardiac arrest – should we just focus on avoiding fever instead?

2 Feb, 14 | by Alistair Lindsay

Prior trials of out-of-hospital cardiac arrest of presumed cardiac etiology have demonstrated improved survival and neurologic function when patients are treated with therapeutic hypothermia. Questions remain as to the optimal target temperature for therapeutic hypothermia. In this international study of patients with out-of-hospital cardiac arrest, 950 patients were randomly assigned to therapeutic hypothermia at a target temperature of either 33°C or 36°C. Treating physicians were aware of the patient’s assignment and all therapies to achieve targets were at the treating center’s discretion. Mean follow-up was 256 days and the primary outcome was death with secondary outcomes including assessments of neurological recovery. No benefit was observed with treatment to target temperature of 33°C. Compared to patients treated to 36°C, patients treated to 33°C had similar mortality (hazard ratio, 1.06; 95% CI, 0.89 to 1.28; P=0.51) and neurologic recovery (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78) Pre-specified sub-group analyses also failed to demonstrate statistically significant differences between the two target temperatures.

Conclusions:

In this study of patients suffering out-of-hospital cardiac arrest, there was no benefit seen in cooling to a target of 33°C as opposed 36°C. This study raises questions as to the benefits of hypothermia in cardiac arrest. It may be that patient cooling results in avoidance of fever and thereby improves outcomes, rather than cooling itself providing patient benefit.

Summarized by Steven M. Bradley and Hussain Contractor

  • Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Åneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Køber L, Langørgen J, Lilja G, Møller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P and Friberg H. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013 Dec 5;369(23):2197-206.

Pharmacogenetic warfarin dosing shows marginal to no benefit

2 Feb, 14 | by Alistair Lindsay

The inter-individual variation in warfarin dosing requirements and narrow therapeutic index for anticoagulation necessitates a personalized dosing regimen. Variation in dosing requirements are in part explained by genetic polymorphism in CYP (involved in warfarin metabolism) and VKOR (a warfarin target) genes. A dosing strategy informed by these polymorphism may hold promise to improve anticoagulation control. In three large randomized trials of similar design, a sophisticated pharmacogenetic approach to warfarin initiation was compared with standard care. All three studies used the percentage of time in therapeutic range as the primary end-point. None of the studies were powered to assess bleeding complications. A genotype-guided dosing approach failed to demonstrate improvements in anticoagulation control for the two largest studies. In the smallest of the three studies, pharmacogenomic-based dosing resulted in a statistically significant benefit (mean percentage of time in therapeutic 67.4% vs. 60.3%, p<0.001). Given the lack of benefit in the larger trials, and the modest effect size observed in the single trial demonstrating benefit, genotype-guided therapy does not appear justified in current practice.

Conclusions:

These studies highlight the challenges care guided by pharmacogenomics. First, genotype currently explains less than half of the variability in response to warfarin. Thus, the potential to predict response to warfarin based on genotype is far from perfect. Further, individual response to warfarin is readily apparent through INR monitoring. When phenotypic responses to therapy (INR for warfarin or blood pressure for antihypertensive therapies) are readily available, it may be difficult for genomic guided therapies to improve on standard care.

Summarized by Steven M. Bradley and Hussain Contractor

  • Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, Rosenberg YD, Eby CS, Madigan RA, McBane RB, Abdel-Rahman SZ, Stevens SM, Yale S, Mohler ER 3rd, Fang MC, Shah V, Horenstein RB, Limdi NA, Muldowney JA 3rd, Gujral J, Delafontaine P, Desnick RJ, Ortel TL, Billett HH, Pendleton RC, Geller NL, Halperin JL, Goldhaber SZ, Caldwell MD, Califf RM and Ellenberg JH. A pharmacogenetic versus a clinical algorithm for warfarin dosing. N Engl J Med. 2013 Dec 12;369(24):2283-93.
  • Pirmohamed M, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, Kesteven P, Christersson C, Wahlström B, Stafberg C, Zhang JE, Leathart JB, Kohnke H, Maitland-van der Zee AH, Williamson PR, Daly AK, Avery P, Kamali F and Wadelius M. A randomized trial of genotype-guided dosing of warfarin. N Engl J Med. 2013 Dec 12;369(24):2294-303.
  • Verhoef TI, Ragia G, de Boer A, Barallon R, Kolovou G, Kolovou V, Konstantinides S, Le Cessie S, Maltezos E, van der Meer FJ, Redekop WK, Remkes M, Rosendaal FR, van Schie RM, Tavridou A, Tziakas D, Wadelius M, Manolopoulos VG and Maitland-van der Zee AH. A randomized trial of genotype-guided dosing of acenocoumarol and phenprocoumon. N Engl J Med. 2013 Dec 12;369(24):2304-12.

Influenza vaccine protects against adverse cardiovascular events

29 Dec, 13 | by Alistair Lindsay

Evidence supporting the use of influenza vaccine in patients at risk for coronary artery events largely comes from observational studies or small randomized trials (RCTs). In this study, the authors conducted a systematic review of 6 RCTs (5 published, 1 unpublished) comparing influenza vaccine to placebo on the rate of a composite of major adverse cardiovascular events (i.e. cardiovascular death or hospitalization for myocardial infarction, unstable angina, stroke, heart failure, or urgent coronary revascularization). The 5 published trials showed a pooled risk ratio (RR) of 0.64 (95% confidence interval [CI] 0.48 – 0.86; p<.003), translating to a number needed to treat of 58 to prevent 1 MACE. In these studies, the vaccine appeared more beneficial in patients with recent acute coronary syndromes (RR 0.45; 95% CI 0.32 – 0.63) compared to those with stable CAD (RR 0.94; 95% CI 0.55 – 1.61; p for interaction =.02). There was no association between receipt of influenza vaccine and cardiovascular mortality (pooled RR 0.81; 95% CI 0.3-1.83) or all-cause mortality (pooled RR 0.85; 95% CI 0.45-1.61). Addition of unpublished data did not change the results.

Conclusions:

Influenza vaccination is associated with a reduced risk for major adverse cardiovascular events, particularly among patients with a recent coronary event. This may signify a readily addressable component of residual risk in patients with coronary disease.

  • Udell JA, Zawi R, Bhatt DL, Keshtkar-Jahromi M, Gaughran F, Phrommintikul A, Ciszewski A, Vakili H, Hoffman EB, Farkouh ME, Cannon CP. Association between influenza vaccination and cardiovascular outcomes in high-risk patients: A meta-analysis. JAMA. 2013;310:1711-1720

Stent type and interrupted anti-platelet therapy does not correlate with adverse events after non-cardiac surgeries

29 Dec, 13 | by Alistair Lindsay

Guidelines recommend delaying elective surgery in patients with drug eluting stent (DES) for one year after stent implantation to allow completion of 1 year of dual anti-platelet therapy (DAPT) without interruption.  This recommendation is based on expert consensus and results in several clinical questions, including whether it is preferable to use a bare metal stent (BMS) in patients with a potential for future surgery and whether this delay is excessive for patients considering surgery with other potential benefits (i.e. knee replacement in patients with life-limiting osteoarthritis).  Accordingly, the authors sought to understand the risk of major adverse cardiovascular events (MACE) following non-cardiac surgery among patients with coronary stents as a function of time since coronary stenting, stent type, and antiplatelet therapy during surgery.

This study was a retrospective cohort of patients undergoing non-cardiac surgery within 2 years of a percutaneous coronary stent procedure.  The authors identified 28,029 patients undergoing non-cardiac surgery within 2 years of coronary stenting.  In this cohort, the 30-day MACE after non-cardiac surgery was 4.7%.  Factors most strongly associated with MACE included non-elective surgery, myocardial infarction in the preceding 6 months, and a revised cardiac risk index of greater than 2.  Timing of surgery in relation to coronary stenting was also associated with MACE, with surgery closer to the time of stenting being associated with increased risk.  In contrast, stent type and antiplatelet cessation was not associated with MACE.

 Conclusions:

Emphasis on stent type and antiplatelet therapy in relation to perioperative cardiac risk may be overblown relative to the risk conferred by the type of surgery and other measures of clinical risk captured in guidelines and risk calculators.  Although this study cannot inform best practices in surgical timing and antiplatelet therapy among patients with coronary stents, it does suggest current guidelines on this issue may inhibit a reasoned and patient-centered approach in conferring the risk-benefit tradeoffs of these clinical decisions.

  •  Hawn MT, Graham LA, Richman JS, Itani KM, Henderson WG, Maddox TM. Risk of major adverse cardiac events following noncardiac surgery in patients with coronary stents. JAMA. 2013;310:1462-1472

 

No clinical outcome benefit from IABP support

29 Dec, 13 | by Alistair Lindsay

The IABP-SHOCK II trial is the largest randomized trial of intra-aortic balloon pump (IABP) counterpulation support in cardiogenic shock.  At 30-days follow-up, this trial demonstrated no mortality reduction.  The current paper reports the longer term outcomes from this trial, given that the benefits of IABP may not be evident in early follow-up.

The IABP-SHOCK II trial was a randomized, open-label, multi-center trial of 600 with cardiogenic shock complicating acute MI and undergoing early revascularization.  At one-year, IABP did not mortality (relative risk [RR] 1.01; 95% confidence interval [CI] 0.86-1.18; p=0.91), reinfarction (RR 2.60; 95% CI 0.95-7.10; p=0.05) recurrent revascularization (RR 0.91, 95% CI 0.58-1.41; p=0.77) or stroke (RR 1.50; 95% CI 0.25-8.84; p=1.00).  Additionally, IABP use did not result in significant differences in quality-of-life measures.  Negative trial results often raise questions about power.  However, as the authors note, the absolute risk difference of 0.4% for mortality between the two groups is very small, there were no indications of benefit in any other outcome variable, and there was a trend toward higher risk of reinfarction in the IABP group.    These together make it unlikely there was a type II error in this study.

Conclusion:

This large trial of IABP counterpulsation for patients with cardiogenic shock complicating acute MI showed no reduction in long-term mortality and raise questions about the clinical utility of IABPs.  Similar trials of newer technologies for left ventricular support are needed to understand if larger increases in cardiac output support may overcome the lack of benefit seen with IABP support.

  •  Thiele H, Zeymer U, Neumann F-J, et al. Intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock (IABP-SHOCK II): final 12 month results of a randomised, open-label trial. The Lancet. 2013;382(9905):1638–1645.

Thrombus aspiration in STEMI fails to demonstrate benefit

29 Dec, 13 | by Alistair Lindsay

Thrombus aspiration during primary PCI for patients presenting with ST elevation myocardial infarction (STEMI) is an intuitively attractive manoeuvre to aid rapid reperfusion, reduce distal embolization and improve microvascular perfusion.  Despite limited trial evidence of clinical benefit, the procedure has quickly taken hold in many PCI centres with European and US guidelines agreeing on a IIa recommendation for its use.

The Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandanvia (TASTE) trial prospectively randomized a total of 7244 patients in an open-label fashion to thrombus aspiration or no thrombus aspiration with all patients receiving conventional treatment with PCI and stenting as indicated.  The trial utilized infrastructure from the pre-existing Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for efficient patient-enrollement and data collection.  At 30 days, thrombus aspiration did not improve mortality (2.8% vs 3.0%; hazard ratio [HR] 0.94; 95% confidence interval [CI] 0.72 to 1.22; P=0.63), myocardial infarction (0.5% vs 0.9%; HR 0.61; 95% CI 0.34 to 1.07; P=0.09) or stent thrombosis (0.2% vs 0.5%; HR 0.47; 95% CI 0.20 to 1.02; P=0.06).

Conclusions

In this large prospective randomized trial, thrombus aspiration failed to demonstrate benefit in patients presenting acutely with STEMI. In a prior study, the clinical benefits of thrombus aspiration were not observed until longer term follow-up and suggest longer follow-up results from the current study may yet reveal benefit.  Further, this trial should be noted for the novel use of registry infrastructure allowing for a low-cost pragmatic clinical trial. This approach to trial design is likely to become more prevalent.

  • Fröbert O, Lagerqvist B, Olivecrona GK, Omerovic E, Gudnason T, Maeng M, Aasa M, Angerås O, Calais F, Danielewicz M, Erlinge D, Hellsten L, Jensen U, Johansson AC, Kåregren A, Nilsson J, Robertson L, Sandhall L, Sjögren I, Ostlund O, Harnek J and  James SK. Thrombus aspiration during ST-segment elevation myocardial infarction. N Engl J Med. 2013 Oct 24;369(17):1587-97.

Latest from Heart

Latest from Heart

Latest Cardiology jobs

Cardiology jobs

Cardiology Masterclasses

Cardiology Masterclasses