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Effect of caloric restriction on heart failure with preserved ejection fraction

2 Feb, 16 | by flee

Therapies that improve outcomes are lacking for heart failure with preserved ejection fraction (HFpEF). The impact of exercise and diet interventions on HFpEF patients has not been studied.  In this single center study of 100 patients,  the effect of caloric restriction (~400 kcal/day) and or aerobic exercise training (3x a week hour long supervised sessions) on co-primary outcomes of exercise capacity (measured by peak oxygen consumption) and quality of life (QOL) (measured by the Minnesota Living with Heart Failure Questionnaire) were evaluated using a 2×2 factorial design,.  Additional exploratory outcomes included: exercise time, 6-minute walk distance, ventilator anaerobic threshold, ventilation/carbon dioxide output slope, other QOL measures (Kansas City Cardiomyopathy Questionnaire, 36-item Short-Form Health Survey), and left ventricular mass and volume. Patient included were obese (BMI >30) with HFpEF (EF ≥ 50%) without segmental wall motion abnormalities, significant valvular or ischemic disease, or pulmonary disease.  The majority of patients in this trial were female, NYHA class II or III, hypertensive, and on diuretic therapy.Both diet and exercise interventions significantly increased exercise capacity (peak VO2, diet 1.3ml/kg body mass/min, 95% CI 0.8-1.8, P <0.001 and exercise, 1.2ml/kg body mass/min, 95% CI, 0.7-1.7, p <0.001) and had an additive effect with improvement in peak VO2 of 2.5ml/kg/min.  There was no difference in QOL by MLHF with either diet or exercise (exercise, -1 unit, 95% -8-5, p 0.7; diet -6 unit, -12-1, p 0.08).

 

Conclusion: Although the 20-week diet and exercise interventions improved peak VO2 amongh patients with HFpEF, the lack of improvement in QOL scores raise questions about the clinical significance of these findings.  While diet and exercise may not significantly impact HRpEF symptoms, optimizing diet and exercise remains central to cardiovascular health.

 

Summarized by Lauren E. Thompson and Steven M. Bradley

 

Kitzman DW, et al. Effect of Caloric Restriction or Aerobic Exercise Training
on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction
A Randomized Clinical Trial. JAMA. 2016 Jan 5;315(1):36-46

COURAGE at 15 years

2 Feb, 16 | by flee

Although PCI improves morbidity and mortality in the context of an acute coronary syndrome, the benefit of PCI in the setting of stable ischemic heart disease appears limited to symptom relief.  This was best demonstrated by the COURAGE trial that randomized 2287 patients with stable angina to either intensive medical therapy alone or medical therapy with PCI.  The study found symptom reduction was greater in the first 6 to 24 months following PCI, but PCI did not impact cardiovascular events or all cause survival.  A prior follow-up study of COURAGE patients suggested mortality at 5 years may have been trending toward benefit with PCI.  In the current study, 15 years of survival data was gathered on 1211 patients (53% of the original cohort) with nearly all of these patients coming from the U.S. Veterans Affairs system.  In this cohort, a total of 561 deaths had occurred in follow-up with 284 deaths (25%) in the PCI group and 277 (24%) in the medical-therapy group (HR, 1.03; 95% CI, 0.83 to 1.21; P=0.76); demonstrating no long-term survival advantage with PCI for stable ischemic heart disease. Data on cause of death and any additional therapies such as PCI or CABG outside of the initial 5yr trial period were unavailable.

 

Conclusions: In 15-year follow-up of approximately half of the original COURAGE trial cohort, there was no difference in mortality between those randomized to PCI and medical therapy.  Ongoing studies will inform whether PCI can improve outcomes beyond symptom burden when targeted to patients with significant demonstrable ischemia.

 

Summarized by Hussain Contractor and Steven M. Bradley

 

Sedlis SP, Hartigan PM, Teo KK, Maron DJ, Spertus JA, Mancini GB, Kostuk W, Chaitman BR, Berman D, Lorin JD, Dada M, Weintraub WS and Boden WE. Effect of PCI on Long-Term Survival in Patients with Stable Ischemic Heart Disease. N Engl J Med. 2015 Nov 12;373(20):1937-46.

Ranolazine ineffective as antianginal following incomplete revascularization

2 Feb, 16 | by flee

Ranolazine is a novel anti-anginal medication that operates via late sodium channel blockade, reducing intracellular calcium during ischemia.  Prior studies suggest ranolazine is effective in reducing the symptoms of angina among patients with ischemic heart disease.  Although revascularization is often used to address symptoms, incomplete revascularization with residual ischemic symptoms is common.  In the current study, the investigators evaluated ranolazine versus placebo in post-PCI patients with incomplete revascularization on the rates of ischemia-driven revascularization or hospitalization.  The investigators enrolled 2651 patients into this trial, randomizing to ranolazine or placebo within 14 days of the index percutaneous intervention.  Patients were included if they had a history of angina and underwent PCI, but were incompletely revascularized (>50% stenosis in at least one lesion in an epicardial vessel greater than 2.0mm in diameter).  The investigators measured time to ischemia-driven revascularization or hospitalization from randomization, as well as endpoints of time to sudden cardiac death, cardiovascular death or myocardial infarction.  After a median follow-up of 643 days, there was no significant difference between placebo and ranolazine for the primary endpoint (hazard ratio 0.95, 95% confidence interval 0.82 – 1.10), or for rates of ischemia-driven or hospitalization.  Results were similar across subgroups, including patients with acute coronary syndromes and those without.  There were higher rates of discontinuation of ranolazine than placebo because of adverse events (14 vs. 11%, p=0.04).

 

Conclusions: Ranolazine was no more effective than placebo in the prevention of ischemia driven revascularization or hospitalization among patients with chronic angina undergoing incomplete revascularization.  These findings raise questions about the relative efficacy of ranolazine to meaningfully improve symptoms among patients with ischemic heart disease.

 

Summarized by Javier A. Valle and Steven M. Bradley

 

Ranolazine in patients with incomplete revascularization after percutaneous coronary intervention (RIVER-PCI): a multicentre, randomized, double-blind placebo-controlled trial.  Weisz et al. Lancet 2016; 387: 136-145

Repair versus replacement for ischemic mitral regurgitation

8 Jan, 16 | by flee

Whether repair or replacement is the preferred approach to surgical correction of ischemic mitral regurgitation is debated.  The Cardiothoracic Surgical Trials Network previously reported 1-year results of a randomized study of these two approached and found no differences echocardiographic or clinical outcomes. This paper reports the 2-year echocardiographic and clinical outcome results from this randomized trial of 251 patients with severe ischemic mitral regurgitation.  At 2 years follow-up, there were no significant differences in mortality (19% after repair versus 23% after replacement; P=0.39). Compared with replacement, the rate of recurrence of moderate or severe mitral regurgitation was significantly higher following repair (58.8% versus 3.8%; P<0.001).  Although the rate of major adverse cardiovascular events did not differ between the groups (42.1% in the repair group versus 42.4% in the replacement group), there were more serious heart failure events following repair (24.0 per 100 patient-years vs. 15.2 per 100 patient-years, P=0.05) and no significant difference in the rate of bleeding events between the two groups (3.5% in the repair group versus 5.3% in the replacement group; P=0.41).

Conclusions

In this study of mitral valve replacement versus repair for ischemic mitral regurgitation, no differences were observed in left ventricular remodeling or mortality at two years of follow-up.  However, there are significant differences in durability with much higher rates of severe mitral regurgitation following repair. The issue of durability as it relates to clinical outcomes will be important to monitor in continued follow-up of this study population.

Summarized by Hussain Contractor and Steven M. Bradley

Goldstein D, Moskowitz AJ, Gelijns AC, Ailawadi G, Parides MK, Perrault LP, Hung JW, Voisine P, Dagenais F, Gillinov AM, Thourani V, Argenziano M, Gammie JS, Mack M, Demers P, Atluri P, Rose EA, O’Sullivan K, Williams DL, Bagiella E, Michler RE, Weisel RD, Miller MA, Geller NL, Taddei-Peters WC, Smith PK, Moquete E, Overbey JR, Kron IL, O’Gara PT, and Acker MA. Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral Regurgitation. N Engl J Med. 2015 Nov 9. [Epub ahead of print]

SPRINT to lower blood pressure targets

8 Jan, 16 | by flee

Epidemiologic studies have demonstrated increasing cardiovascular risk at a systolic blood pressure above 115 mmHg.  However, blood pressure treatment targets are less clear with clinical trials limited to evidence of benefit below 150mmHg. The Systolic Blood Pressure Intervention Trial (SPRINT) sought to determine outcomes following treatment to a target of less than 120mmHg (intensive treatment) compared with a target of less than 140mmHg (standard treatment).   The study randomized 9361 non-diabetic patients with systolic hypertension (>130mmHg) and at least one other cardiac risk factor.  The primary outcome was a composite of major adverse cardiovascular events or cardiovascular death. The choice of pharmacological agents was not mandated, but the use of a thiazide based regimen was encouraged.  At 1-year, the mean systolic blood pressures were 121.4mmHg in the intensive treatment group and 136.2mmHg in the standard treatment group. The mean number of blood pressure medications required in the intensive treatment group was 2.8 compared with 1.8 in the standard treatment group.  The trial was stopped early in response to a strong signal of benefit with treatment to less than 120mmHg for the primary outcome (1.65% per year vs. 2.19% per year; hazard ratio 0.75; 95% confidence interval, 0.64 to 0.89; P<0.001).  This benefit was observed at a median follow-up of 3.26 years.  In addition, all-cause mortality was lower in the intensive treatment group (hazard ratio, 0.73; 95% confidence interval 0.60 to 0.90; P = 0.003).   Rates of hypotension, syncope, electrolyte disturbance, and acute renal failure were higher in the intensive treatment group.

Conclusions

In this large randomized study of non-diabetic patients with systolic hypertension, treating blood pressure to a target of 120mmHg led to significant cardiovascular and mortality benefits.  Translating these results into real-world practice without the intensive monitoring associated with a clinical trial is likely to be challenging, but holds the potential to significantly improve health outcomes in the general population.

Summarized by Hussain Contractor and Steven M. Bradley

Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE, Kimmel PL, Johnson KC, Goff DC Jr, Fine LJ, Cutler JA, Cushman WC, Cheung AK, Ambrosius WT. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015 Nov 26;373(22):2103-16.

Increased radiation exposure with transradial access for coronary procedures

8 Dec, 15 | by flee

Compared with the transfemoral approach, coronary angiography and percutaneous coronary intervention (PCI) performed via transradial access reduces rates of bleeding and vascular complications.  However, the potential for increased radiation exposure to patients and operators may be a barrier to the adoption of the transradial approach.  In this systematic review and meta-analysis of 24 published studies comparing transradial and transfemoral access for coronary angiography and PCI, the authors compared the differences in radiation exposure between access approaches as measured by fluoroscopy time (min) and kerma-area product (KAP, Gy cm2).  After a rigorous search to identify studies of coronary procedural access that reported radiation exposure, the authors found 24 published randomized controlled trials from 1996-2014 with 19,328 patients for analysis.  Comparing radiation exposure by access site strategy, the authors found a statistically significant increase in fluoroscopy time for diagnostic coronary angiography (DCA) (weighted mean difference [WMD]: 1.04 min [95% CI 0.84-1.24]) and PCI (WMD fluoroscopy time 1.15 min [95% CI 0.96–1.33]), while only a statistically significant increase in KAP for PCI (0.55 Gy cm2 [95% CI 0.08–1.02] but not DCA (1.72 Gy cm2 [95% CI −0.10 – 3.55]. In meta-regression analysis comparing differences in radiation exposure by year of study, differences in fluoroscopy time between transradial and transfemoral approaches decreased over time.  The analysis was limited by significant heterogeneity in the pooled studies (I2 > 75%).

 

Conclusion: This systematic review and meta-analysis suggests transradial access for coronary procedures is associated with a small increase in radiation exposure.  However, this gap in radiation exposure between transradial and transfemoral access has closed over time, presumably reflecting increased operator experience with transradial access.  Further, the clinical significance of the observed difference in radiation exposure is unclear. Given the benefits of transradial access for reducing rates of periprocedural complications, these findings should not discourage use of transradial access.  Instead, these findings emphasize the importance of continued attention to radiation safety as operators adopt a transradial approach.

 

Summarized by Javier A. Valle and Steven M. Bradley

 

Plourde G, Pancholy SB, Nolan J, Jolly S, Rao SV, et al. Radiation exposure in relation to the arterial access site used for diagnostic coronary angiography and percutaneous coronary intervention: a systematic review and meta-analysis

Lancet 2015; 386: 2192–203

Long-term data on fractional flow reserve guided PCI

8 Dec, 15 | by flee

The Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) trial was a landmark study of the use of fractional flow reserve (FFR) to guide coronary revascularization through the identification of ischemia-inducing stenosis at the time of coronary angiography. The previously published 1- and 2-year results of the FAME trial demonstrated fewer major adverse cardiac events in the FFR arm as compared to patients undergoing revascularization guided by angiographic assessment alone.  In the current study, the authors present the 5-year follow-up data from the FAME trial.  The original trial enrolled 1005 patients across 20 centers from 2006 to 2007, with 496 randomized to angiography-guided revascularization and 506 to FFR-guided revascularization.  Of these patients, 429 in the angiography-guided arm and 436 in the FFR-guided arm were included in the 5-year follow-up (86% overall).  At 5 years, there was no difference between treatment arms for major adverse cardiac events (31% angiography vs. 28% FFR, relative risk 0.91 [95% CI 0.75-1.10]), or individual outcomes of all cause mortality, myocardial infarction, or coronary revascularization. Similarly, cardiac mortality was not significantly different between treatment arms (16% angiography vs. 13% FFR, p= 0.21).  A sensitivity analysis in which death was assumed for lost-to-follow-up patients demonstrated similar findings.

 

Conclusions: At 5-years follow up, FFR-guided revascularization demonstrated similar outcomes when compared with revascularization guided by angiography alone.  These findings provide reassurance that the early benefits of FFR targeted revascularization are not overwhelmed by late events.

 

Summarized by Javier A. Valle and Steven M. Bradley

 

van Nunen LX, Zimmermann FM, Tonino PAL, Barbato E, Baumbach A, Engstrøm T, et al. Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial. Lancet 2015; 386: 1853–60.

Sub-clinical valve thrombosis in the setting of bioprosthetic aortic valves

25 Nov, 15 | by flee

Bioprosthetic aortic valves have played a critical role in improving both quality of life and prognosis in patients with severe aortic valve disease. Implanted either surgically (SAVR) or percutaneously (TAVI), they provide restoration of valve function without the need for anticoagulation as required with mechanical valves.  This study was the result of clinical evaluation of a patient with a stroke soon after TAVI.  This evaluation included CT imaging of the bioprosthetic valve which revealed restricted leaflet mobility and prompted further inquiry.  Using data from a TAVI randomized trial and 2 registries of patients with both TAVI and SAVR, the authors went on to evaluate 187 patients who underwent CT and echocardiographic imaging during the first 12 months after bioprosthetic valve implantation in the aortic position.  The authors found reduced leaflet motion was not uncommon with 40% of patients in the clinical trial and 13% in the two registries having findings of moderate to severe restriction in 1 or more valve leaflets.  Although the cause of restricted motion could not be determined definitively, imaging suggested thrombus at the base of the valve leaflets that impaired normal leaflet excursion.  The possibility that thrombus was the causal factors was further suggested by the lack of impaired leaflet motion in any patient who was anticoagulated with warfarin.  In addition, among patients with restricted leaflet motion, restoration of leaflet motion was found in 100% of patients who were subsequently started on warfarin as compared with 10% of patients not anticoagulated (P<0.001).  Interestingly, abnormalities in leaflet motion could not be seen on standard transthoracic echo imaging and there was no evidence of an increased gradient across valves with restricted leaflet motion by CT or TEE.  The clinical consequences of this finding remain unclear with no increase in stroke or TIA patients with restricted leaflet motion, although the sample size was small.

Conclusion

Using advanced imaging techniques, reduced motion of bioprosthetic aortic valves was commonly observed and suggestive of subclinical valve thrombosis.  The clinical consequences of this finding remain uncertain and further study is warranted to ascertain optimal imaging approaches and management of this finding.

Summarized by Hussain Contractor and Steven M. Bradley

Makkar RR, Fontana G, Jilaihawi H, Chakravarty T, Kofoed KF, de Backer O, Asch FM, Ruiz CE, Olsen NT, Trento A, Friedman J, Berman D, Cheng W, Kashif M, Jelnin V, Kliger CA, Guo H, Pichard AD, Weissman NJ, Kapadia S, Manasse E, Bhatt DL, Leon MB, Søndergaard L. Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves. N Engl J Med. 2015 Oct 5. [Epub ahead of print]

Absorbable stents non-inferior….but is that enough?

25 Nov, 15 | by flee

A coronary artery stent that scaffolds the vessel immediately after angioplasty but disappears over time has been proposed as means to avoid complications of late stent thrombosis and restore physiological vasomotion.  Bioabsorbable platforms (termed scaffolds) are designed to slowly dissolve over 2 to 3 years, leaving little or no residue in the vessel.  However, conventional stent technology sets a very high bar with low rates of late complications, many years of operator experience, and large numbers of prior trials.  In the ABSORB III trial a total of 2008 patients with stable or unstable angina were randomized in a 2:1 fashion to revascularization with either the ABSORB bioabsorbable scaffold or a conventional drug-eluting stent (in this case the everolimus-eluting XIENCE platform).  The study was designed as a non-inferiority trial with a primary end-point of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization.  At 1 year of follow-up, the study demonstrated no significant difference in the primary end-point (7.8% vs. 6.1%, P=0.007 for noninferiority and P=0.16 for superiority) and no significant difference between the two groups in the individual components of the end-point.  However, it the point-estimates for adverse events were higher among patients receiving the bioabsorbable scaffold.

Conclusions

In this large study comparing first generation bioabsorbable coronary scaffolds against conventional third generation metallic drug-eluting stents, the bioabsorbable scaffolds demonstrated non-inferiority within the pre-specified margin of 4.5% in terms of both efficacy and safety.  However, the point estimates for bioabsorbable scaffolds in this trial raise concern about the true benefits, and even potential for harm, of this new technology.  Longer term data in larger studies is needed prior to wholesale adoption of absorbable coronary scaffolds in clinical practice.

Summarized by Hussain Contractor and Steven M. Bradley

Ellis SG, Kereiakes DJ, Metzger DC, Caputo RP, Rizik DG, Teirstein PS, Litt MR, Kini A, Kabour A, Marx SO, Popma JJ, McGreevy R, Zhang Z, Simonton C, Stone GW; ABSORB III Investigators. Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease. N Engl J Med. 2015 Oct 12. [Epub ahead of print]

Similar Outcomes with Bivalirudin and Unfractionated Heparin During PCI for Acute Coronary Syndromes

4 Nov, 15 | by flee

Approximately two-thirds of all PCI are performed for acute coronary syndromes.  In this setting, the optimal balance of anticoagulation to avoid thrombosis against the risk of major bleeding is a pivotal area of procedural management.  Multiple clinical trials have compared bivalirudin and heparin (+/- IIb/IIIa inhibitor), but the optimal strategy remains debated.  In particular, changes in clinical practice, namely increasing use of radial access and decreasing use of IIb/IIIa inhibitors, may influence the optimal antithrombotic treatment strategy.  In the MATRIX trial, 7213 patients with an acute coronary syndrome (55% with ST-elevation) were randomly allocated to receive either bivalirudin or heparin at 70-100u/kg peri-procedurally with an additional randomization step at procedural completion to either stop bivalirudin or continue the infusion for 4 to 6 hours.  Approximately 25% of the heparin group also received a IIb/IIIa inhibitor at the treating physician’s discretion.  There was no significant difference in rates of major adverse cardiovascular events between the bivalirudin and heparin groups (10.3% vs. 10.9%; RR, 0.94; 95% CI, 0.81 to 1.09; P=0.44), nor was there any difference in safety outcomes between the two arms (P=0.12).  In addition, prolonging bivalirudin infusion made no difference to clinical outcomes with no change in rates of stent thrombosis or other adverse clinical events (P=0.34).

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