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.

Stenting of atherosclerotic renal artery disease fails to improve outcomes

13 Apr, 14 | by Alistair Lindsay

Atherosclerotic renal-artery stenosis is common among patients with cardiovascular disease and the condition may contribute to hypertension. The impact of renal artery angioplasty or stenting on the risk of clinical events among patients with atherosclerotic renal disease remains poorly defined. In the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study, 947 patients atherosclerotic renal-artery stenosis and hypertension and/or chronic kidney disease were randomized to medical therapy alone or medical therapy plus renal artery stenting.  The primary composite end-point included cardiovascular and renal death, myocardial infarction, stroke and progressive renal failure.  Over a median follow-up of 43 months, there was no difference in the rate of the composite outcome in patients treated with renal artery stenting compared with medical therapy alone (35.1% vs. 35.8%,; hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58).  Further, individual components of the composite end-point were similar for both treatment groups.

Conclusions

In this large randomized trial, renal artery stenting for atherosclerotic stenosis failed to demonstrate clinical benefit.  These findings call into question a commonly performed, invasive, and costly procedure for patients with renal-artery atherosclerotic stenosis and suggest similar outcomes can be obtained with optimal medical management.

Summarized by Steven M. Bradley and Hussain Contractor

  • Cooper CJ1, Murphy TP, Cutlip DE, Jamerson K, Henrich W, Reid DM, Cohen DJ, Matsumoto AH, Steffes M, Jaff MR, Prince MR, Lewis EF, Tuttle KR, Shapiro JI, Rundback JH, Massaro JM, D’Agostino RB Sr and Dworkin LD.  Stenting and medical therapy for atherosclerotic renal-artery stenosis.  N Engl J Med. 2014 Jan 2;370(1):13-22.

No renal protection with low-dose dopamine or nesiritide in acute heart failure

13 Apr, 14 | by Alistair Lindsay

Diuresis to decongest patients with acute heart failure (AHF) is particularly challenging in the setting of renal dysfunction, as these patients are at risk of worsening renal function.  Small studies have suggested that low-dose dopamine or nesiritide may increase urine output and maintain renal function in such patients. The Renal Optimization Strategies Evaluation (ROSE) trial randomized 360 patients with AHF and renal dysfunction (GFR 15-60ml/min/1.73m2) to nesiritide, low-dose dopamine, or placebo in addition to an intravenous loop diuretic. Primary outcomes included urine volume and change in cystatin C at 72-hours post-randomization. Compared to placebo, patients randomized to low-dose dopamine had similar 72-hour urine volumes (8524mL vs. 8296mL, p=0.59) and cystatin C levels (0.12 vs. 0.11mg/L, p=0.72). In addition, there was no change in weight or creatinine at 72 hours. Similarly, patients randomized to low-dose nesiritide demonstrated no better 72-hour urine volumes (8574 mL vs. 8296 mL, p=0.49), cystatin C levels (0.07 vs. 0.11 mg/L, p=0.36), weight or creatinine.

Conclusion

These findings suggest neither low-dose dopamine nor nesiritide are effective as adjuvant renal therapies in patients with AHF and renal dysfunction. A therapy that allows for diuresis without angering the nephron remains elusive.

Summarized by Steven M. Bradley and Supriya Shore

 

Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigran MJ, Goldsmith SR, Bart BA, Bull DA, Stehlik J, LeWinter MM, Konstam MA, Huggins GS, Rouleau JL, O’Meara E, Tang WH, Starling RC, Butler J, Deswal A, Felker GM, O’Connor CM, Bonita RE, Margulies KB, Cappola TP, Ofili EO, Mann DL, Dávila-Román VG, McNulty SE, Borlaug BA, Velazquez EJ, Lee KL, Shah MR, Hernandez AF, Braunwald E, Redfield MM; NHLBI Heart Failure Clinical Research Network. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial. JAMA. 2013 Dec 18;310(23):2533-43. doi: 10.1001/jama.2013.282190.

Treatment of obstructive sleep apnea lowers blood pressure

13 Apr, 14 | by Alistair Lindsay

More than 70% of patients with resistant hypertension have obstructive sleep apnea (OSA). However, whether continuous positive airway pressure (CPAP) for OSA improves blood pressure in patients with resistant hypertension is unknown.  This was a randomized controlled trial of CPAP in 194 patients with resistant hypertension in the setting of OSA. The primary outcome was the change in 24-hour ambulatory mean blood pressure (AMBP) from baseline to 12 weeks post-randomization. Medical therapy used for resistant hypertension did not differ between the two groups. Patients treated with CPAP showed a greater decrease in 24-hour AMBP (3.1mmHg, 95% CI 0.6-5.6mmHg, p=.02). In analyses restricted to patients tolerant of CPAP, akin to an on-treatment analysis, the intervention resulted in a larger decrease in AMBP (4.4mmHg, 95% CI 1.8-7mmHg). Furthermore, each hour of CPAP use was associated with a 1.3 mmHg decrease in AMBP.

Conclusion

Among patients with OSA and resistant hypertension, CPAP therapy for 12 weeks resulted in improvements in 24-hour ambulatory blood pressure. The degree of blood pressure change was small, but could have meaningful effects on cardiovascular mortality.

 Summarized by Steven M. Bradley and Supriya Shore

  • Martínez-García MA, Capote F, Campos-Rodríguez F, Lloberes P, Díaz de Atauri MJ, Somoza M, Masa JF, González M, Sacristán L, Barbé F, Durán-Cantolla J, Aizpuru F, Mañas E, Barreiro B, Mosteiro M, Cebrián JJ, de la Peña M, García-Río F, Maimó A, Zapater J, Hernández C, Grau SanMarti N, Montserrat JM; Spanish Sleep Network. Effect of CPAP on blood pressure in patients with obstructive sleep apnea and resistant hypertension: the HIPARCO randomized clinical trial. JAMA. 2013 Dec 11;310(22):2407-15.

Pre-hospital Epinephrine for Witnessed Cardiac Arrest: Improved Outcomes?

13 Apr, 14 | by Alistair Lindsay

Epinepherine remains a common part of resuscitation care for cardiac arrest, despite a lack of clinical evidence to suggest it improves patient survival.  This study was a retrospective cohort of patients in Japan with witnessed out-of-hospital cardiac arrest.  From this cohort, 1990 matched pairs of patients with initial rhythm of ventricular tachycardia or ventricular fibrillation (VT/VF) and 9058 pairs with non-VT/VF were created on the basis of the propensity for administration of epinephrine by emergency medical services.  The outcome was survival and neurological status at one month or at discharge.  In the propensity matched analysis, epinephrine was associated with greater survival in patients with VF/VT (17.0% versus 13.4%; adjusted odds ratio [OR] 1.36, 95% confidence interval [CI] 1.13 – 1.63) and in patients with non-VF/VT arrest (4.0% versus 2.4%; adjusted OR 1.78, 95% CI 1.49 – 2.13).  The difference in neurologically intact survival was not significant for VF/VT (6.6% versus 6.6%) or non-VF/VT arrest (0.7% versus 0.4%; adjusted OR 1.55, 95% CI 0.99 – 2.41).

Conclusion

Administration of pre-hospital epinephrine for witnessed cardiac arrest is associated with increased overall survival in this propensity matched observational study.  However, given the lack of association with neurologically intact survival, questions remain as to whether epinephrine improves outcomes that are desired by patients.  Randomized study of this important question is warranted.

 Summarized by Steven M. Bradley and Preston M. Schneider

  • Nakahara S, Tomio J, Takahashi H, et al. Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study. BMJ. 2013;347.

Sudden increase in LVAD thrombosis rates

13 Apr, 14 | by Alistair Lindsay

The left ventricular assist device (LVAD) has rapidly been incorporated into the management of patients with advanced heart failure.  In response to an internal audit demonstrating a rapid increase in the incidence of pump thrombosis following implantation of HeartMate II LVADs, the authors pooled data from additional centers to investigate this trend.  The resultant retrospective analysis of 895 HeartMate II LVADs implanted in 837 patients identified 72 confirmed pump thrombosis in 66 patients and an additional 36 suspected thrombosis. Starting in the spring of 2011, the incidence of thrombosis at 3 months from implant rose from 2.2% to 8.4% by early 2013.  Levels of LDH and in particular a doubling in levels in the previous week were highly predictive of thrombosis.  Thrombosis was associated with substantial morbidity and mortality with 11 patients receiving urgent transplantation and a further 20 requiring pump replacement.  Mortality in those not undergoing a surgical procedure was 48.2% in the following 6 months. 

Conclusions

The incidence of thrombosis in the HeartMate II LVAD device has increased dramatically since early 2011 and is associated with substantial morbidity and mortality.  Of note, anticoagulation protocols changed during the course of this analysis, but continued inquiry is required to understand the underlying cause of these findings.  This study speaks to the importance of real-world surveillance of device therapies to continually ensure their optimal use and safety for patient benefit.

 Summarized by Steven M. Bradley and Hussain Contractor

  •  Starling RC, Moazami N, Silvestry SC, Ewald G, Rogers JG, Milano CA, Rame JE, Acker MA, Blackstone EH, Ehrlinger J, Thuita L, Mountis MM, Soltesz EG, Lytle BW, Smedira NG. Unexpected abrupt increase in left ventricular assist device thrombosis. N Engl J Med. 2014 Jan 2;370(1):33-40.

 

 

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.

Latest from Heart

Latest from Heart

Cardiology Masterclasses

Cardiology Masterclasses