Baylor Heart and Vascular Institute

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.

Roberts, P. R., N. Clementy, F. Al Samadi, C. Garweg, J. L. Martinez-Sande, S. Iacopino, J. B. Johansen, X. Vinolas Prat, R. C. Kowal, D. Klug, L. Mont, J. Steffel, S. Li, D. Van Osch and M. F. El-Chami (2017). “A leadless pacemaker in the real-world setting: The micra transcatheter pacing system post-approval registry.” Heart Rhythm 14(9): 1375-1379.

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BACKGROUND: First-in-man studies of leadless pacemakers have demonstrated high rates of implant success, and safety and efficacy objectives were achieved. Outside of the investigational setting, there are concerns, particularly over cardiac effusion and perforation, device dislodgement, infection, telemetry, and battery issues. OBJECTIVE: The acute performance of the Micra transcatheter pacemaker from a worldwide Post-Approval Registry is reported. METHODS: The registry is an ongoing prospective single-arm observational study designed to assess the safety and effectiveness of Micra in the post-approval setting. The safety end point was system- or procedure-related major complications at 30 days post implant. We compared the major complication rate with that of the 726 patients from the investigational study. Electrical performance was also characterized. RESULTS: The device was successfully implanted in 792 of 795 registry patients (99.6%) by 149 implanters at 96 centers in 20 countries. Through 30 days post implant, a total of 13 major complications occurred in 12 patients, for a major complication rate of 1.51% (95% confidence interval, 0.78%-2.62%). Major complications included cardiac effusion/perforation (1, 0.13%), device dislodgement (1, 0.13%), and sepsis (1, 0.13%). After adjusting for baseline differences, the rate of major complications in the registry trended lower than the investigational trial (odds ratio, 0.58, 95% confidence interval, 0.27-1.25; P = .16). Early pacing capture thresholds were low and stable. CONCLUSION: Performance of the Micra transcatheter pacemaker in a real-world setting demonstrates a high rate (99.6%) of implant success and low rate (1.51%) of major complications through 30 days post implant. In particular, the rates of pericardial effusion, device dislodgement, and infection were low, reinforcing the positive results seen in the investigational study.

Gottlieb, R. L., T. Sam, S. Y. Wada, J. F. Trotter, S. K. Asrani, B. Lima, S. M. Joseph, G. Gonzalez-Stawinski and S. A. Hall (2017). “Rational heart transplant from hepatitis c donor: New antiviral weapons conquer the trojan.” J Card Fail: 2017 Aug [Epub ahead of print].

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BACKGROUND: Donors with hepatitis C (HCV) viremia are rarely utilized for orthotopic heart transplantation (OHTx) due to post-transplant risks. New, highly effective HCV antivirals may alter the landscape. METHODS: An adult patient unsuitable for bridging mechanical support therapy accepted a heart transplant offer from a donor with HCV viremia. Upon daily logarithmic rise in HCV viral load and adequate titers to ensure successful genotyping, once daily sofosbuvir 400 mg / velpatasvir 100 mg (Epclusa) was initiated empirically pending HCV genotype (genotype 3a confirmed after initiation of therapy). RESULTS: We report the kinetics of acute Hepatitis C viremia and therapeutic response to treatment with a new pangenotypic antiviral agent after donor-derived acute HCV infection transmitted incidental to successful cardiac transplant into a HCV negative OHTx recipient. Prompt resolution of viremia was noted by the first week of a 12 week course of antiviral therapy. Sustained virologic remission continues beyond 12 weeks after completion of HCV therapy (SVR-12). CONCLUSIONS: The availability of effective pangenotypic therapy for HCV may expand donor availability. The feasibility of early versus late treatment of HCV remains to be determined through formalized protocols. We hypothesize pharmacoeconomics to be the greatest limitation to widespread availability of this promising tool.

Kopecky, K., A. Afzal, J. Felius, S. A. Hall, J. C. Mendez, M. Assar, D. P. Mason and A. S. Bindra (2017). “Bilateral sympathectomy for treatment of refractory ventricular tachycardia.” Pacing Clin Electrophysiol: 2017 Aug [Epub ahead of print].

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Ventricular tachycardia (VT) commonly occurs in patients with ischemic or non-ischemic cardiomyopathy and requires anti-arrhythmic drugs, ablation or advanced circulatory support. However, life-threatening VT may be refractory to these therapies, and may cause frequent implantable cardioverter defibrillator (ICD) discharges. Left cardiac sympathetic denervation reduces the occurrence of these fatal arrhythmias by inhibiting the sympathetic outflow to the cardiac tissue. We present a 69-year-old man with non-ischemic cardiomyopathy, life-threatening VT, and hemodynamic instability with numerous ICD discharges who remained refractory to antiarrhythmic drug therapy and ablation attempts. He was effectively treated with bilateral cardiac sympathectomy. Six months later, he remained free of VT with no ICD discharges.