Cardiology

Mack, M. J., M. A. Acker, A. C. Gelijns, J. R. Overbey, M. K. Parides, J. N. Browndyke, M. A. Groh, A. J. Moskowitz, N. O. Jeffries, G. Ailawadi, V. H. Thourani, E. G. Moquete, A. Iribarne, P. Voisine, L. P. Perrault, M. E. Bowdish, M. Bilello, C. Davatzikos, R. F. Mangusan, R. A. Winkle, P. K. Smith, R. E. Michler, M. A. Miller, K. L. O’Sullivan, W. C. Taddei-Peters, E. A. Rose, R. D. Weisel, K. L. Furie, E. Bagiella, C. S. Moy, P. T. O’Gara and S. R. Messe (2017). “Effect of cerebral embolic protection devices on cns infarction in surgical aortic valve replacement: A randomized clinical trial.” Jama 318(6): 536-547.

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Importance: Stroke is a major complication of surgical aortic valve replacement (SAVR). Objective: To determine the efficacy and adverse effects of cerebral embolic protection devices in reducing ischemic central nervous system (CNS) injury during SAVR. Design, Setting, and Participants: A randomized clinical trial of patients with calcific aortic stenosis undergoing SAVR at 18 North American centers between March 2015 and July 2016. The end of follow-up was December 2016. Interventions: Use of 1 of 2 cerebral embolic protection devices (n = 118 for suction-based extraction and n = 133 for intra-aortic filtration device) vs a standard aortic cannula (control; n = 132) at the time of SAVR. Main Outcomes and Measures: The primary end point was freedom from clinical or radiographic CNS infarction at 7 days (+/- 3 days) after the procedure. Secondary end points included a composite of mortality, clinical ischemic stroke, and acute kidney injury within 30 days after surgery; delirium; mortality; serious adverse events; and neurocognition. Results: Among 383 randomized patients (mean age, 73.9 years; 38.4% women; 368 [96.1%] completed the trial), the rate of freedom from CNS infarction at 7 days was 32.0% with suction-based extraction vs 33.3% with control (between-group difference, -1.3%; 95% CI, -13.8% to 11.2%) and 25.6% with intra-aortic filtration vs 32.4% with control (between-group difference, -6.9%; 95% CI, -17.9% to 4.2%). The 30-day composite end point was not significantly different between suction-based extraction and control (21.4% vs 24.2%, respectively; between-group difference, -2.8% [95% CI, -13.5% to 7.9%]) nor between intra-aortic filtration and control (33.3% vs 23.7%; between-group difference, 9.7% [95% CI, -1.2% to 20.5%]). There were no significant differences in mortality (3.4% for suction-based extraction vs 1.7% for control; and 2.3% for intra-aortic filtration vs 1.5% for control) or clinical stroke (5.1% for suction-based extraction vs 5.8% for control; and 8.3% for intra-aortic filtration vs 6.1% for control). Delirium at postoperative day 7 was 6.3% for suction-based extraction vs 15.3% for control (between-group difference, -9.1%; 95% CI, -17.1% to -1.0%) and 8.1% for intra-aortic filtration vs 15.6% for control (between-group difference, -7.4%; 95% CI, -15.5% to 0.6%). Mortality and overall serious adverse events at 90 days were not significantly different across groups. Patients in the intra-aortic filtration group vs patients in the control group experienced significantly more acute kidney injury events (14 vs 4, respectively; P = .02) and cardiac arrhythmias (57 vs 30; P = .004). Conclusions and Relevance: Among patients undergoing SAVR, cerebral embolic protection devices compared with a standard aortic cannula did not significantly reduce the risk of CNS infarction at 7 days. Potential benefits for reduction in delirium, cognition, and symptomatic stroke merit larger trials with longer follow-up.

Townsend, R. R., F. Mahfoud, D. E. Kandzari, K. Kario, S. Pocock, M. A. Weber, S. Ewen, K. Tsioufis, D. Tousoulis, A. S. P. Sharp, A. F. Watkinson, R. E. Schmieder, A. Schmid, J. W. Choi, C. East, A. Walton, I. Hopper, D. L. Cohen, R. Wilensky, D. P. Lee, A. Ma, C. M. Devireddy, J. P. Lea, P. C. Lurz, K. Fengler, J. Davies, N. Chapman, S. A. Cohen, V. DeBruin, M. Fahy, D. E. Jones, M. Rothman and M. Bohm (2017). “Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (spyral htn-off med): A randomised, sham-controlled, proof-of-concept trial.” Lancet: 2017 Aug [Epub ahead of print].

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BACKGROUND: Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. METHODS: SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. FINDINGS: Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5.5 mm Hg (95% CI -9.1 to -2.0; p=0.0031), 24-h DBP -4.8 mm Hg (-7.0 to -2.6; p<0.0001), office SBP -10.0 mm Hg (-15.1 to -4.9; p=0.0004), and office DBP -5.3 mm Hg (-7.8 to -2.7; p=0.0002). No significant changes were seen in the sham-control group: 24-h SBP -0.5 mm Hg (95% CI -3.9 to 2.9; p=0.7644), 24-h DBP -0.4 mm Hg (-2.2 to 1.4; p=0.6448), office SBP -2.3 mm Hg (-6.1 to 1.6; p=0.2381), and office DBP -0.3 mm Hg (-2.9 to 2.2; p=0.8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5.0 mm Hg (95% CI -9.9 to -0.2; p=0.0414), 24-h DBP -4.4 mm Hg (-7.2 to -1.6; p=0.0024), office SBP -7.7 mm Hg (-14.0 to -1.5; p=0.0155), and office DBP -4.9 mm Hg (-8.5 to -1.4; p=0.0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group. INTERPRETATION: Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation.

Mack, M. J. and R. Stoler (2017). “Intervention for aortic stenosis: The measurement of frailty matters.” J Am Coll Cardiol 70(6): 701-703.

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Frailty is a relatively common condition in patients with cardiovascular disease. This condition, which includes impairment of multiple physiological systems, occurs more frequently with advancing age and is particularly relevant when these patients undergo cardiovascular interventions or surgery. As a general rule of thumb, the more invasive the procedure and the older the patient, the more that frailty matters in terms of influencing procedure outcomes, recovery, and benefit. There are multiple risk models that have accuracy in predicting early, 30-day outcomes after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) (1 2) . Although a wide spectrum of patient factors and comorbid disease conditions are used as covariates in constructing these predictive algorithms, measures of frailty have not been routinely included. The reasons for lack of inclusion include the wide variety of tools available to measure frailty, a lack of a consensus on which tools to use, and the burden and time required to perform the tests, leading to variability and incompleteness of collection. In addition, routine use has been hampered by the lack of a solid evidence base for the measurement of frailty really having value in determining the ability of a patient to undergo a procedure successfully and withstand the associated systemic and physiological insults that may preclude full recovery. However, with the advent of less-invasive procedures, which offer treatment options to patients previously not considered candidates, measurement of frailty in the elderly population has assumed greater import. The 2014 American Heart Association/American College of Cardiology Guideline for the Management of Patients with Valvular Heart Disease (3) included frailty, major organ system dysfunction, and procedure-specific impediments as adjunctive to the Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) in risk assessment in patients under consideration for treatment (4) . The tools most commonly used in current clinical evaluation of patients with aortic stenosis are the measurement of gait speed using the 5-m walk test and the Fried Criteria, which measure 4 domains of frailty, including mobility, strength, nutritional status, and habitual activity.

Mack, M. and P. Grayburn (2017). “Guideline-directed medical therapy for secondary mitral regurgitation: More questions than answers!” JACC Heart Fail 5(9): 660-662.

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Secondary (also known as functional) mitral regurgitation (MR) is common in heart failure patients. Secondary MR is not caused by a primary abnormality of the mitral leaflets but rather to dilation/dysfunction of the left ventricle (LV). As a result, there is apical-lateral displacement of the papillary muscles resulting in tethering of the mitral leaflets and subsequent failure of anatomically normal leaflets to coapt (1) . Secondary MR results in further LV volume overload and a resulting vicious cycle of more severe MR leading to further LV dilation and congestive heart failure. This mechanism of MR is termed type IIIb in the Carpentier classification of mitral valve leaflet motion and can be due to both ischemic and nonischemic dilated cardiomyopathies (2) . The mainstay of therapy is guideline-directed medical therapy (GDMT) for heart failure including diuretics, beta blockers, aldosterone antagonists, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocking agents. It is an area of intense interest in the fields of surgery and medical device therapy because of the overall poor prognosis with medical therapy alone. Although it is widely recognized that secondary MR is associated with a worse prognosis in heart failure patients, it remains uncertain whether surgical correction of the MR and breaking the “vicious cycle” changes the dismal course of the disease.

Mooney, J., S. L. Sellers, P. Blanke, P. Pibarot, R. T. Hahn, D. Dvir, P. S. Douglas, N. J. Weissman, S. K. Kodali, V. H. Thourani, H. Jilaihawi, O. Khalique, C. R. Smith, S. H. Kueh, M. Ohana, R. Grover, C. Naoum, A. Crowley, W. A. Jaber, M. C. Alu, R. Parvataneni, M. Mack, J. G. Webb, M. B. Leon and J. A. Leipsic (2017). “Ct-defined prosthesis-patient mismatch downgrades frequency and severity, and demonstrates no association with adverse outcomes after transcatheter aortic valve replacement.” JACC Cardiovasc Interv 10(15): 1578-1587.

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OBJECTIVES: This study sought to determine if indexed effective orifice area (EOAi), using left ventricular outflow tract measured from computed tomography (EOAiCT), reclassified prosthesis-patient mismatch (PPM) compared with conventional echocardiogram-defined measurements (EOAiTTE). BACKGROUND: PPM does not predict mortality following transcatheter aortic valve replacement (TAVR). However, it is unknown if the EOAiCT of the left ventricular outflow tract improves risk stratification. METHODS: A total of 765 TAVR patients from the PARTNER II (Placement of Aortic Transcatheter Valves II) trial S3i cohort were evaluated. EOAi was calculated using the continuity equation, and the left ventricular outflow tract area was derived from baseline computed tomography. Traditional echocardiographic categories defined PPM: absent (>0.85 cm2/m2), moderate (>/=0.65 and