Cardiology

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 390(10108): 2160-2170.

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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.

Roberts, W. C., T. M. Becker and S. A. Hall (2017). “Usefulness of total 12-lead qrs voltage as a clue to diagnosis of patients with cardiac sarcoidosis severe enough to warrant orthotopic heart transplant.” JAMA Cardiol: 2017 Nov [Epub ahead of print].

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Importance: Severe heart failure caused by cardiac sarcoidosis is difficult to diagnosis without biopsy. Objective: To assess whether total electrocardiographic 12-lead QRS voltage may be a clue to diagnosis. Design, Setting, Participants: Case-series study with cases collected at Baylor University Medical Center at Dallas, Dallas, Texas, from January 13, 2005, to January 24, 2017. The clinical records of 16 patients with severe heart failure caused by cardiac sarcoidosis were studied. Examination of total 12-lead electrocardiographic QRS voltage (peak of the R wave to the nadir of either the Q or S wave, whichever was deeper) was performed prior to orthotopic heart transplant (OHT). Gross and microscopic pathologic specimens of the native hearts were studied. Main Outcomes and Measures: The primary outcome was to correlate the total 12-lead QRS voltage measurement with various morphologic features in the native diseased heart. Results: The 16-patient study group consisted of 8 men and 8 women; 12 (75%) were white and 4 (25%) were black. At the time of OHT, patient age ranged from 50 to 67 years (mean, 57 years). Cardiac sarcoidosis was diagnosed by pre-OHT biopsy results in 2 (13%) patients and by examination of the native heart after OHT in 14 (87%) patients. Total nonpaced 12-lead QRS voltage mean was 117 mm (range, 52-155 mm) for 8 patients and total paced 12-lead QRS voltage was 90 mm (range, 67-161 mm) for 12 patients. These low mean values were similar to those of patients with carcinoid heart disease (mean [SD], 105 [40] mm), cardiac amyloidosis (104 [35] mm), and severe cardiac adiposity (120 [31] mm) studied at necropsy or after OHT. In contrast, mean (SD) values were 323 (109) mm in patients with massive cardiomegaly, 257 mm in patients with severe aortic stenosis, 272 (86) mm in patients with severe pure aortic regurgitation, 220 (67) mm in patients with severe pure mitral regurgitation, 197 (64) mm in patients with hypertrophic cardiomyopathy, and 153 (40) mm in patients with idiopathic dilated cardiomyopathy. Conclusions and Relevance: Most patients diagnosed with cardiac sarcoidosis causing severe heart failure and warranting OHT had low total 12-lead QRS voltage measurements despite having native hearts of increased weight. This finding may provide a clue to the diagnosis of this disease.

Packer, M. (2017). “The imminent demise of cardiovascular drug development.” JAMA Cardiol: 2017 Nov [Epub ahead of print].

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The development of new cardiovascular drugs is at its deepest nadir in decades.¹ Major pharmaceutical companies have ended research activities in cardiology,² and applications to and approvals by the US Food and Drug Administration for new cardiovascular pharmaceuticals have declined dramatically even as innovations in other therapeutic areas have soared.

Sorajja, P., S. Vemulapalli, T. Feldman, M. Mack, D. R. Holmes, Jr., A. Stebbins, S. Kar, V. Thourani and G. Ailawadi (2017). “Outcomes with transcatheter mitral valve repair in the united states: An sts/acc tvt registry report.” J Am Coll Cardiol 70(19): 2315-2327.

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BACKGROUND: Post-market surveillance is needed to evaluate the real-world clinical effectiveness and safety of U.S. Food and Drug Administration-approved devices. OBJECTIVES: The authors examined the commercial experience with transcatheter mitral valve repair for the treatment of mitral regurgitation. METHODS: Data from the Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy Registry on patients commercially treated with transcatheter mitral valve repair were analyzed. The study population consisted of 2,952 patients treated at 145 hospitals between November 2013 and September 2015. In 1,867 patients, data were linked to patient-specific Centers for Medicare and Medicaid Services administrative claims for analyses. RESULTS: The median age was 82 years (55.8% men), with a median Society of Thoracic Surgery predicted risk of mortality of 6.1% (interquartile range: 3.7% to 9.9%) and 9.2% (interquartile range: 6.0% to 14.1%) for mitral repair and replacement, respectively. Overall, in-hospital mortality was 2.7%. Acute procedure success occurred in 91.8%. Among the patients with Centers for Medicare and Medicaid Services linkage data, the mortality at 30 days and at 1 year was 5.2% and 25.8%, respectively, and repeat hospitalization for heart failure at 1 year occurred in 20.2%. Variables associated with mortality or rehospitalization for heart failure after multivariate adjustment were increasing age, lower baseline left ventricular ejection fraction, worse post-procedural mitral regurgitation, moderate or severe lung disease, dialysis, and severe tricuspid regurgitation. CONCLUSIONS: Our findings demonstrate that commercial transcatheter mitral valve repair is being performed in the United States with acute effectiveness and safety. Our findings may help determine which patients have favorable long-term outcomes with this therapy.

Cedars, A., C. Vanderpluym, D. Koehl, R. Cantor, S. Kutty and J. K. Kirklin (2017). “An interagency registry for mechanically assisted circulatory support (intermacs) analysis of hospitalization, functional status, and mortality after mechanical circulatory support in adults with congenital heart disease.” J Heart Lung Transplant: 2017 Nov [Epub ahead of print].

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BACKGROUND: Adult congenital heart disease (ACHD) prevalence is increasing worldwide, with advanced heart failure (HF) as a leading cause of death. Limited data are available on durable mechanical circulatory support (MCS) in ACHD patients. METHODS: ACHD patients from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database were identified and propensity matched with non-ACHD patients using risk factors from the INTERMACS Seventh Annual Report. We compared these groups for the primary outcome of post-MCS mortality. We also investigated adverse event rates, functional status, and health-related quality of life. RESULTS: ACHD (n = 128) and non-ACHD (n = 512) patients were appropriately matched by baseline characteristics. ACHD patients had a longer length of stay at MCS implant (24 vs 19 days, p = 0.006) but similar rates of post-MCS adverse events and hospitalization. There were similar improvements in functional status and health related quality of life post-MCS in both groups. ACHD patients had significantly higher mortality post-MCS exclusively during the first 5 months after implant (p = 0.003) and a lower probability of receiving a transplant (p = 0.003). Risk factors for early mortality were biventricular or total artificial heart device implant and age > 50 years. CONCLUSIONS: ACHD patients experience a higher early mortality after MCS but have similar adverse event rates and similar improvements in functional capacity and quality of life compared with non-ACHD patients. These data support expansion of MCS use in selected ACHD patients.