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Renal denervation misses the mark in resistant hypertension

8 Jun, 14 | by Alistair Lindsay

The prospect of percutaneous renal-artery denervation to treat hypertension has been widely heralded in response to pilot studies that demonstrated marked reductions in blood pressure after renal denervation.  Despite the rapid adoption of catheter-based renal artery denervation, data from large scale randomised controlled trials remains absent.  A total of  535 patients with severe resistant hypertension were randomized in a 2:1 ratio to renal denervation or a sham procedure consisting of renal angiography alone.  All study patients were receiving a minimum of three antihypertensive medications, including a diuretic, with persistently elevated systolic blood pressures of 160mmHg or more. The primary end point was the change in office systolic blood pressure at 6 months.  The change in mean 24-hour ambulatory systolic pressure at 6 months was used as a secondary end-point.   Compared with the sham procedure, renal-artery denervation resulted in no significant reductions in blood pressure as determined by office measurement of systolic pressure (-14.13±23.93 mm Hg vs -11.74±25.94 mm Hg; difference of -2.39 mm Hg, 95% confidence interval [CI] -6.89 to 2.12; P=0.26) or mean 24-ambulatory pressure (-6.75±15.11 mmHg vs. -4.79±17.25 mmHg; difference of -1.96 mm Hg, 95% CI, -4.97 to 1.06; P=0.98).

Conclusions

In this large-scale, sham-controlled, blinded trial, renal denervation did not result in significant blood pressure reductions.  These findings call into question the utility of renal-denervation as part of current clinical practice.

  • Bhatt DL, Kandzari DE, O’Neill WW, D’Agostino R, Flack JM, Katzen BT, Leon MB, Liu M, Mauri L, Negoita M, Cohen SA, Oparil S, Rocha-Singh K, Townsend RR, Bakris GL; SYMPLICITY HTN-3 Investigators.  . A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014 Apr 10;370(15):1393-401.

Summarized by Steven M. Bradley and Hussain Contractor

 

Cardiac resynchronization therapy benefit holds up in clinical practice

8 Jun, 14 | by Alistair Lindsay

The benefit of cardiac resynchronization therapy with a defibrillator (CRT-D) relative to implantable cardioverter-defibrillator (ICD) therapy alone has not been evaluated in routine clinical practice.  This study used data from the National Cardiovascular Data Registry’s ICD Registry linked with Medicare claims data to compare outcomes after CRT-D and ICD implantation in community practice.  The analysis included 7090 propensity matched patients who underwent either CRT-D or ICD implantation between 2006 and 2009 at one of 780 U.S. hospitals participating in the NCDR ICD registry.  Patients were over age 65 and met criteria for CRT-D implantation (left ventricular ejection fraction ≤ 35% and QRS duration ≥ 120ms). Over 3 years of follow-up, CRT-D was associated with lower risk of mortality (HR 0.82, 99% CI 0.73-0.93), all-cause readmission (HR 0.86, 99% CI 0.81-0.93), and heart failure readmission (HR 0.78, 99% CI 0.69-0.88) compared with ICD therapy.  However, CRT-D was also associated with a higher risk of device related infection (HR 1.90, 99% CI 1.07–3.37).  In subgroup analyses, the reduced risk of heart failure readmission was most prominent among patients with left bundle branch block or QRS duration of at least 150 ms.

 Conclusions

In routine clinical practice, patients who were eligible for CRT-D therapy according to criteria based on the findings of clinical trials experienced better long-term outcomes than patients treated with ICD alone.  These findings suggest the benefits observed in highly controlled clinical trials of CRT-D have translated into patient benefit in for properly selected patients in routine clinical practice

  • Masoudi FA, Mi X, Curtis LH, Peterson PN, Curtis JP, Fonarow GC, Hammill SC, Heidenreich PA, Al-Khatib SM, Piccini JP, Qualls LG, Hernandez AF. Comparative Effectiveness of Cardiac Resynchronization Therapy With an Implantable Cardioverter-Defibrillator Versus Defibrillator Therapy Alone. A Cohort StudyComparative Effectiveness of Cardiac Resynchronization Therapy. Annals of Internal Medicine. 2014;160:603–611.

Summarized by Steven M. Bradley and Preston M. Schneider

 

β-blockers beneficial in some, but not all, ischemic heart disease patients undergoing non-cardiac surgery

8 Jun, 14 | by Alistair Lindsay

Whether β-blockers reduce adverse events among patients with stable ischemic heart disease (IHD) undergoing non-cardiac surgery remains in debate. In this Danish study, the authors retrospectively identified 28,263 IHD patients who underwent non-cardiac surgeries and examined the association between pre-procedural β-blockers use and a major adverse cardiovascular event (MACE) defined as 30-day cardiac death, myocardial infarction (MI) and stroke. The cohort included 7,990 patients (28.3%) with heart failure and 12,601 (44.6%) with a history of MI.  Overall, 1,374 (4.9%) experienced a MACE. The risk for MACE was lower among patients treated with β-blockers in the setting of a history of heart failure (adjusted hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.66-0.91) but not among patients without heart failure (adjusted HR 1.11; 95% CI 0.92-1.13). Among patients without heart failure, use of β-blockers was associated with lower risk of MACE in patients with an MI in the prior 2 years (HR 0.54; 95% CI 0.37-0.78).

Conclusion: In this retrospective cohort study of patients with IHD, β-blocker use prior to non-cardiac surgery was associated with a lower 30-day risk for major adverse events among patients with heart failure or recent MI. However, lower risk patients without heart failure or recent MI did not appear to benefit from perioperative β-blocker use.  Questions about the optimal IHD risk-threshold for consideration of β-blocker use in the setting of non-cardiac surgery remain.

  •  Andersson C, Merie C, Jorgensen M, et al. Association of beta-blocker therapy with risks of adverse cardiovascular events and deaths in patients with ischemic heart disease undergoing noncardiac surgery: a Danish nationwide cohort study. JAMA Internal Medicine. Mar 2014;174(3):336-344.

Summarized by Steven M. Bradley and Supriya Shore

 

 

Glycemic measurements are not helpful in CVD risk prediction among non-diabetics

8 Jun, 14 | by Alistair Lindsay

Several clinical guidelines recommend measurement of glycated hemoglobin (HbA1c) to guide cardiovascular risk (CVD) risk assessment. In this study, the authors examined the utility of adding HbA1c measurements to conventional risk factors in prediction of CVD among non-diabetic patients. Data from 73 prospective studies with nearly 300,000 non-diabetic patients without known CVD at enrollment was analyzed. Mean age was 58 years, 49% were women and mean HbA1c was 5.4%. Over a median follow-up duration of nearly 10 years, there were 20,840 fatal and nonfatal incident CVD events. Addition of HbA1c levels to risk prediction models with conventional CVD risk factors of age, sex, smoking, blood pressure, HDL and total cholesterol led to small changes in C-index (0.7434 to 0.7452; change of 0.0018, 95% CI 0.0003-0.0033) and net reclassification 0.42 (-0.63 to 1.48). Use of other glycemic measurements such as fasting glucose, random glucose and postload glucose were no better for CVD risk prediction than HbA1c.

Conclusions

Contrary to existing guidelines, addition of HbA1c levels to traditional CVD risk factors did not lead to meaningful improvement in CVD risk prediction among non-diabetics in this large, multicenter prospective study.

  • Emerging Risk Factors Collaboration,  Di Angelantonio E, Gao P, et al. Glycated hemoglobin measurement and prediction of cardiovascular disease. JAMA. Mar 26 2014;311(12):1225-1233

Summarized by Steven M. Bradley and Supriya Shore

 

Warfarin for atrial fibrillation in patients with chronic kidney disease – does the thromboembolic benefit outweigh the bleeding risk?

8 Jun, 14 | by Alistair Lindsay

Chronic kidney disease (CKD) predisposes to high risks for both thrombo-embolism and bleeding. As a result, understanding the risk-benefit profile for use of anticoagulation therapies among CKD patients with atrial fibrillation is important to optimize patient outcomes. However, clinical trials evaluating efficacy and safety of anti-coagulants for atrial fibrillation generally exclude CKD patients and observational studies have had conflicting results. Accordingly, this prospective cohort study of 24,317 atrial fibrillation patients admitted with myocardial infarction in Sweden examined the association between warfarin therapy and patient outcomes by stage of CKD. Warfarin was prescribed in 21.8% patients and CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2) was present in 51.7%. Compared with patients not treated with warfarin, the risk-adjusted composite outcome of death, myocardial infarction, or ischemic stroke was lower at 1 year of follow-up among patients treated with warfarin, regardless of CKD class. This reduction in thromboembolic events was not offset by an increased risk of bleeding events.

Conclusions

This study confirms the benefit of warfarin for thromboembolic risk protection in patients with CKD and atrial fibrillation. However, given that warfarin is known to increase bleeding risk, the lack of apparent bleeding risk with warfarin therapy in this study raises concerns that baseline bleeding risk was markedly lower among patients treated with warfarin. Given the increasing prevalence of both CKD and atrial fibrillation, a better understanding of the risk-benefit profile of anticoagulation in these high risk patients is needed.

  • Carrero JJ, Evans M, Szummer K, et al. Warfarin, kidney dysfunction, and outcomes following acute myocardial infarction in patients with atrial fibrillation. JAMA. Mar 5 2014;311(9):919-928.

Summarized by Steven M. Bradley and Supriya Shore

 

Cardiac device deactivation rarely mentioned in advanced directives

13 Apr, 14 | by Alistair Lindsay

The authors retrospectively reviewed medical records of 150 patients who underwent deactivation of a pacemaker or implantable cardioverter-defibrillator in a four-year period at a single tertiary care center. These were older patients (median age 79) and 99% had a poor or terminal prognosis. More than half of the patients had an advance directive, yet only 1 patient explicitly mentioned device deactivation in their advanced directive. Surrogates for the patient made more than half of the requests for device deactivation (51%). Median survival after device deactivation was 2 days (IQR 0-483).

Conclusion

The intersection of implantable cardiac devices and end-of-life care is certain to become more frequent.  The current study highlights an important gap in addressing these devices as part of advance directives and end-of-life planning, leaving surrogates frequently burdened with the decision of device deactivation.

Summarized by Steven M. Bradley and Supriya Shore

  • Buchhalter LC, Ottenberg AL, Webster TL, et al. Features and outcomes of patients who underwent cardiac device deactivation. JAMA Intern Med. 2014 Jan;174(1):80-5.

Coronary artery calcium density is inversely associated with coronary risk

13 Apr, 14 | by Alistair Lindsay

 

Coronary calcium is associated with cardiovascular disease risk.  However, it may not only be the volume, but the density of coronary calcium that influences risk as more dense calcium may reflect stable plaque at lower risk of inciting coronary events.  The traditional Agatson method of scoring coronary calcium burden does not consider coronary calcium volume and density independently. In this prospective cohort study of 3,398 adults without known cardiovascular disease, the authors examined the predictive value of adding coronary calcium density to Agatston volume scores for cardiovascular disease risk. Over a median follow-up of more than 7 years, there were 265 cardiovascular events in the study population and the Agatston volume score of coronary calcium was positively associated with cardiovascular disease risk. However, the density score was inversely associated with cardiovascular disease risk. Furthermore, the addition of the density score improved a risk prediction model for cardiovascular disease.

 Conclusion

Coronary density appears to refine cardiovascular disease risk estimation using coronary calcium scoring, with more dense calcium reflecting stable plaques at lower risk.

  •  Criqui MH, Denenberg JO, Ix JH, et al. Calcium density of coronary artery plaque and risk of incident cardiovascular events. JAMA. 2014 Jan 15;311(3):271-8.

Mesenchymal stem cells may improve quality of life for patients with ischemic cardiomyopathy

13 Apr, 14 | by Alistair Lindsay

In this study, patients with chronic ischemic cardiomyopathy and EF <50% on optimal medical therapy were randomized to autologous culture expanded mesenchymal cells (=22), autologous bone marrow mononuclear cells (n=22) or placebo vehicle (n=21) delivered by transendocardial stem cell injection (TESI). There were no serious adverse events among any patients undergoing a TESI procedure. Rates of major adverse cardiovascular events did not vary between groups. A possible signal of improved quality of life was observed following treatment with either of the cell types.  At one year, a repeated measures model demonstrated the Minnesota Living with Heart Failure score had improved following treatment with mesenchymal (-6.3; 95% CI -15.0 to 2.4, P=.02) or bone marrow cells (-8.2; 95% CI -17.4 to 0.97, P=.005) but not in the placebo group (0.4; 95% CI -9.45 to 10.25, P=.38). Only mesenchymal cells decreased scar size as a percentage of the LV mass (-18.9%; 95% CI  -30.4 to -7.4, P=.004).

Conclusion

Transendocardial injection of both mesenchymal and bone marrow cells for ischemic cardiomyopathy was safe in this small initial trial.  Signals of quality of life improvement with these therapies are encouraging.  However, this enthusiasm must be tempered against a change in quality of life scores that is at the low end of clinical significance and the performance of multiple comparisons in the study analysis.

Summarized by Steven M. Bradley and Supriya Shore

  • Heldman AW, DiFede DL, Fishman JE, et al. Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA. 2014;311(1):62-73.

Pre-hospital cooling with saline infusion does not improve cardiac arrest outcomes

13 Apr, 14 | by Alistair Lindsay

Prior randomized trials have established hypothermia as a promising therapy to improve outcomes of cardiac arrest.  It has been suggested that the benefit of hypothermia may be increased through early initiation of cooling in the field prior to hospital arrival.  In this trial, 1,364 patients with out-of-hospital cardiac arrest were randomized to usual care or pre-hospital cooling with infusion of cold normal saline immediately after return of spontaneous circulation. The intervention was associated with a reduction in core temperature, but no change in clinical outcomes. Among patients with arrest in the setting of ventricular fibrillation, there were no differences between patients treated with cold saline vs control in survival to discharge (62.7% vs. 64.3%, P.69) or neurologic recovery (57.5% vs. 61.9%, P=.69). Similarly, among patients without ventricular fibrillation, the proportion of patients surviving to discharge (19.2% vs 16.3%, P=.30) or with neurological recovery (14.4% vs. 13.4%, P=.30) did not differ between the intervention and control groups.

Conclusions

In this randomized trial of pre-hospital cooling of patients with out-of-hospital cardiac arrest, this therapy resulted in no improvements in clinical outcomes despite more rapid reduction of core temperature.  As the method of achieving reductions in core temperature may influence the benefit of this therapy, alternate approaches to cooling that do not result in expansion of patient intravascular volume should be considered.

 Summarized by Steven M. Bradley and Supriya Shore

  • Kim F, Nichol G, Maynard C, et al. Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial. JAMA. 2014 Jan 1;311(1):45-52.

Multivitamins of no benefit for secondary prevention

13 Apr, 14 | by Alistair Lindsay

A healthy diet that includes foods rich in antioxidants and vitamins has consistently been associated with lower risk of atherosclerosis.  Whether secondary risk reduction can be achieved with oral vitamin supplementation is unclear.  The TACT (Trial to Assess Chelation Therapy) study was a 2×2 factorial design randomized trial to assess the impact of chelation therapy or multivitamin supplementation on cardiovascular outcomes among patients with a history of cardiovascular disease.  This study reports the outcomes of the multivitamin supplementation compared with placebo.  The primary endpoint was composite of death from any cause, reinfarction, stroke, coronary revascularization, or hospitalization for angina.  The pre-specified secondary endpoint was the composite of cardiovascular death, reinfarction, or stroke.  Patients were intended to take high dose oral multivitamins or placebo for 5 years, however the study suffered from significant drop out in both arms.  Of the 1708 patients randomized, only about 800 received the assigned treatment for more than 3 years.  The outcomes were assessed using intention-to-treat analysis, and showed no significant differences between groups for the primary or secondary end points. 

Conclusions

While the results of this study must be interpreted with caution due to the high drop-out rate and any signal of benefit (or harm) could be obscured. However, this study agrees with the growing literature that suggests no benefit of vitamin supplementation for secondary cardiovascular risk reduction.

 Summarized by Steven M. Bradley and Preston M. Schneider

  • Lamas GA, Boineau R, Goertz C, et al. Oral High-Dose Multivitamins and Minerals After Myocardial Infarction: A Randomized Trial. Annals of Internal Medicine. 2013;159(12):797–805. doi:10.7326/0003-4819-159-12-201312170-00004.

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