Association between statin exposure and diabetes incidence among privately-insured patients before and after applying a novel technique to control for selection bias.

INTRODUCTION: The association between statins and incident diabetes mellitus (DM) in observational studies is much larger than that reported from randomized controlled trials. We sought to assess this association using a novel design controlling for selection bias. METHODS: Using data from MarketScan, we identified a cohort of non-diabetic patients who initiated a statin and matched them to patients not taking statins. From the statin-user cohort, we identified two subgroups: patients who received statin refills for >6 months (continuers) and patients who received statin refills <6 months (discontinuers). Patients were followed for a minimum of two years to determine incident DM. RESULTS: We included 442,526 patients, divided equally between statin users and non-users. Statin use was associated with increased DM (9.9% vs. 4.4%, HR 2.2, p < 0.001). Among the 221,263 statin users, there were 194,357 continuers and 26,906 discontinuers. There was no significant difference in the incidence rate of DM between both groups (10.0% vs. 9.3%, HR 1.03, p = 0.22). CONCLUSIONS: Statin use was strongly associated with incident diabetes when users were compared to non-users but not when continuers were compared to discontinuers. Selection bias confounds the association between statin use and incident diabetes in observational studies.

Catheter-Directed Mechanical Thrombectomy in Massive Pulmonary Embolism With Cardiogenic Shock.

We discuss a patient who presented with cardiogenic shock secondary to massive pulmonary embolism and right ventricular failure. She was managed by a multidisciplinary heart team and treated with catheter-directed thrombectomy, followed by ProtekDuo (Tandem [Liva Nova], London, United Kingdom) heart percutaneous right ventricular support leading to complete recovery from this often fatal condition. (Level of Difficulty: Intermediate.).

Association between pulmonary function and left ventricular volume and function in duchenne muscular dystrophy.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is characterized by absence of the subsarcolemmal protein dystrophin, present in skeletal muscles and cardiomyocytes. We hypothesized that progressive respiratory and left ventricular (LV) insufficiencies in DMD could be parallel and interrelated phenomena. METHODS: We conducted a retrospective chart review of 27 patients with DMD. Our primary objective was to compare the rates of decline between pulmonary function test (PFT) measures (forced expiratory volume in the first second, forced vital capacity, peak expiratory flow rate, maximal inspiratory/expiratory pressure) and echocardiographic estimates of LV end-diastolic volume and LV ejection fraction. RESULTS: The rates of decline/year of PFTs and LV estimates were not significantly different. Pulmonary function test measures of ventilatory efficiency and strength had strong intercorrelations. Pulmonary function tests and LV estimates had weak but statistically significant correlations. DISCUSSION: A comparable rate of decline in PFTs and LV indices in DMD provides evidence for concurrently progressive deterioration in respiratory and LV functions. Muscle Nerve, 2019.

X-ray canary in the cath lab: Posterior cataracts.

Cataract formation in the posterior subcapsular region of the lens is a lesion highly specific to both high-dose acute radiation exposure and chronic low-dose exposure. Low-dose radiation may not manifest lens changes for several decades after initial exposure. Cardiac catheterization team members need to be educated on, and protected from, this form of radiation injury as its long latency period between exposure and physical damage may acutely reduce the sense of hazard amongst healthcare radiation workers.

Beta-1 vs. beta-2 adrenergic control of coronary blood flow during isometric handgrip exercise in humans.

During exercise, ß-adrenergic receptors are activated throughout the body. In healthy humans, the net effect of ß-adrenergic stimulation is an increase in coronary blood flow. However, the role of vascular ß1 vs. ß2 receptors in coronary exercise hyperemia is not clear. In this study, we simultaneously measured noninvasive indexes of myocardial oxygen supply (i.e., blood velocity in the left anterior descending coronary artery; Doppler echocardiography) and demand [i.e., rate pressure product (RPP) = heart rate × systolic blood pressure) and tested the hypothesis that ß1 blockade with esmolol improves coronary exercise hyperemia compared with nonselective ß-blockade with propranolol. Eight healthy young men received intravenous infusions of esmolol, propranolol, and saline on three separate days in a single-blind, randomized, crossover design. During each infusion, subjects performed isometric handgrip exercise until fatigue. Blood pressure, heart rate, and coronary blood velocity (CBV) were measured continuously, and RPP was calculated. Changes in parameters from baseline were compared with paired t-tests. Esmolol (Δ = 3296 ± 1204) and propranolol (Δ = 2997 ± 699) caused similar reductions in peak RPP compared with saline (Δ = 5384 ± 1865). In support of our hypothesis, ΔCBV with esmolol was significantly greater than with propranolol (7.3 ± 2.4 vs. 4.5 ± 1.6 cm/s; P = 0.002). This effect was also evident when normalizing ΔCBV to ΔRPP. In summary, not only does selective ß1 blockade reduce myocardial oxygen demand during exercise, but it also unveils ß2-receptor-mediated coronary exercise hyperemia.NEW & NOTEWORTHY In this study, we evaluated the role of vascular ß1 vs. ß2 receptors in coronary exercise hyperemia in a single-blind, randomized, crossover study in healthy men. In response to isometric handgrip exercise, blood flow velocity in the left anterior descending coronary artery was significantly greater with esmolol compared with propranolol. These findings increase our understanding of the individual and combined roles of coronary ß1 and ß2 adrenergic receptors in humans.

Esmolol infusion versus propranolol infusion: effects on heart rate and blood pressure in healthy volunteers.

Despite its widespread clinical use, the ß1-adrenergic receptor antagonist esmolol hydrochloride is not commonly used in human physiology research, and the effective dose of esmolol (compared with the nonselective ß-blocker propranolol) is unclear. In four separate studies we used cycle ergometry exercise and infusions of isoproterenol and epinephrine to test the heart rate (HR)-lowering effect of esmolol compared with propranolol and saline in healthy humans. In cohort 1, both esmolol (ΔHR 57 ± 6 beats/min) and propranolol (ΔHR 56 ± 7 beats/min) attenuated exercise tachycardia compared with saline (ΔHR 88 ± 17 beats/min). In cohort 2, we found that the HR response to exercise was similar at 5 min (ΔHR 57 ± 9 beats/min) and 60 min (ΔHR 55 ± 9 beats/min) after initiation of the esmolol maintenance infusion. In cohort 3, we confirmed that the HR-lowering effect of esmolol disappeared 45 min after termination of the maintenance infusion. In cohort 4, changes in femoral blood flow and hematological parameters in response to epinephrine infusion were not different between esmolol and saline infusion, indicating that our esmolol infusion paradigm does not block ß2-receptors. Collectively, our data indicate that infusion of ~160 mg of esmolol (range 110-200 mg in the 5 min before exercise) acutely and selectively blocks ß1-receptors in healthy humans. Additionally, ß1-receptors remain blocked 60 min later if a maintenance infusion of ~0.2 mg·kg total body mass-1·min-1 continues. The current data lay the foundation for future studies to evaluate ß1- vs. ß2-receptor control of the circulation in humans.NEW & NOTEWORTHY We used cycle ergometry exercise and infusions of isoproterenol and epinephrine to test the heart rate-lowering effect of esmolol compared with propranolol and saline in healthy humans. Collectively, our data indicate that infusion of ~160 mg of esmolol (range 110-200 mg in the 5 min before exercise) acutely and selectively blocks ß1-adrenergic receptors. These infusion parameters can be used in future experiments to evaluate ß1- vs. ß2-receptor control of the circulation in humans.

Cardiovascular disease risk assessment and prevention: current guidelines and limitations.

Even after decades of progress in understanding atherosclerotic cardiovascular disease (ASCVD) and improved cardiovascular event prevention, the incidence, consequences and cost of cardiovascular disease (CVD) remain a significant public health issue. Observational studies have identified major ASCVD risk factors and lead to the development of a number of risk assessment systems/scores now in use. However many patients who will develop clinically important CVD are not identified by current systems or approaches and significant numbers of recurrent cardiovascular events continue to occur even after aggressive secondary prevention treatment strategies are utilized. Some now term this residual risk. The statin era revolutionized clinical practice with effective outcome-driven risk reduction. As a result there are now numerous clinical recommendations or guidelines for ASCVD risk stratification and treatment. Further disease and event prevention may rely on improved patient-centered risk stratification using novel biomarkers, imaging techniques, and new treatment approaches including emerging pharmacologic therapies.