Newer Drugs to Reduce High Blood Pressure and Mitigate Hypertensive Target Organ Damage.

PURPOSE OF REVIEW: This review aims to investigate the blood pressure (BP)-lowering effects of emerging drugs developed to treat diabetic kidney disease and heart failure (HF). We summarize the potential pathophysiological mechanisms responsible for mitigating hypertensive target organ damage and evaluating the available clinical data on these newer drugs. RECENT FINDINGS: Nonsteroidal dihydropyridine-based mineralocorticoid receptor antagonists (MRAs), dual angiotensin II receptor-neprilysin inhibitors (valsartan with sacubitril), sodium-glucose cotransporter 2 inhibitors (SGLT2i), and soluble guanylate cyclase stimulators are new classes of chemical agents that have distinct mechanisms of action and have been shown to be effective for the treatment of cardiovascular (CV) disease (CVD), HF, and type 2 diabetes mellitus (T2D). These drugs can be used either alone or in combination with other antihypertensive and CV drugs. Among these, SGLT2i and valsartan with sacubitril offer new avenues to reduce CVD mortality. SGLT2i have a mild-to-moderate effect on BP lowering with a favorable effect on CV and renal hemodynamics and have been shown to produce a significant reduction in the incidence of major adverse CVD events (as monotherapy or add-on therapy) compared with controls (placebo or non-SGLT2i treatment). Most of the participants in these studies had hypertension (HTN) at baseline and were receiving antihypertensive therapy, including renin-angiotensin system blockers. The combination of valsartan with sacubitril also lowers BP in the short term and has demonstrated a striking reduction in CVD mortality and morbidity in HF patients with a reduced left ventricular ejection fraction. If widely adopted, these novel therapeutic agents hold significant promise for reducing the public health burden posed by HTN and CVD. Based on the results of several clinical trials and considering the high prevalence of HTN and T2D, these new classes of agents have emerged as powerful therapeutic tools in managing and lowering the BP of patients with diabetic kidney disease and HF.

Cardiac sarcoidosis in monozygotic twins: An opportunity for early surveillance and treatment.

Genetic factors play an important role in the development of cardiac sarcoidosis and may determine disease pattern, severity, and prognosis. A 55-year-old African American male presented with new onset of congestive heart failure. This patient was diagnosed with pulmonary sarcoidosis eleven years prior and initially treated with prednisone. He was lost to follow-up until this index admission. He had a monozygotic twin brother who was diagnosed with pulmonary and cardiac sarcoidosis, and passed away from severe biventricular dysfunction. Surveillance, with echocardiography or cardiac MRI, in siblings at high risk of sarcoidosis may allow for early detection and treatment.

Torsades de pointes with high-dose loperamide.

CASE: A 41year-old male presented with torsades de pointes. The patient was taking over 100mg of loperamide per day to self-medicate for chronic pain. Coronary angiography, cardiac magnetic resonance imaging, and genetic testing were negative for pre-disposing ischemia, cardiomyopathy, or genetic variant respectively. CONCLUSIONS: Patients without predisposing genetic or cardiac abnormalities are at risk of life-threatening QTc prolongation and torsades with use of high-dose loperamide. The authors suggest consideration of regulating the quantity of loperamide that can be purchased at a single time similar to the regulations in place for other over-the-counter medications with high potential for misuse.

Rapid atrial pacing above the maximum sensor rate: a case report.

Background: While ventricular-based timing modes are known to cause elevated atrial pacing above the lower rate when intrinsic atrioventricular (AV) conduction is shorter than programmed AV delay, there is one case report in 2015 by Jafri et al. where rapid atrial pacing was induced in an Abbott device set DDI with a lower rate of 90 by an unsensed premature atrial complex and slow intrinsic AV conduction allowing pacemaker 'crossover.' Case summary: We present a very unusual case of rapid atrial pacing at >180 b.p.m. due to a perfect storm of events that we believe has not been previously reported. A patient with a St. Jude Abbott DCPPM set DDDR had an atrial tachyarrhythmia causing a mode switch to DDIR, which uses ventricular-based timing. This was followed by a period of rapid atrial pacing that terminated spontaneously. Discussion: This phenomenon depended on an initial atrial tachyarrhythmia causing a mode switch to DDIR. In addition, the set lower rate would not have led to a short enough calculated ventriculo-atrial interval (VAI), but because rate responsive pacing was enabled, the calculated VAI was short enough to promote the crossover in setting of slow AV conduction and allow the rapid atrial pacing. Understanding this unique mechanism requires careful attention to pacemaker timing cycles and appreciation of the limitations of device programming. While it appears that a similar phenomenon was reported once in the literature, we believe that this episode of rapid atrial pacing was even more serendipitous due to the unlikely series of events required for its inception.

Arrhythmia Following Pulse Generator Change: What Is the Mechanism?

We present an unusual case of a "reverse" pacemaker-mediated endless loop arrhythmia with native atrioventricular conduction serving as the anterograde limb of the tachycardia circuit and the atrial depolarization stimulated by the pacemaker in response to the sensed ventricular QRS. The electrocardiogram findings can be explained by lead reversal in the header during pulse generator change, with the ventricular lead connected to the atrial port and the atrial lead connected to the ventricular port. Careful examination of the electrocardiogram with attention to the 2 closely spaced pacing stimuli separated by the paced atrioventricular delay provided an important clue for diagnosis this case.

Echocardiographic Investigation of Low-Flow State in a Hispanic/Latino Population.

Objective: To assess the prevalence of low-flow state (LFS) with left ventricular (LV) stroke volume index of less than 35 mL/m2 and the demographics, clinical and echocardiographic characteristics associated with LV remodeling and function in a Hispanic/Latino population. Participants and Methods: The study included 1346 asymptomatic participants from the Hispanic Community Health Study/Study of Latinos with normal LV ejection fraction (≥55%) and no valvular heart disease. LV volume, mass and left atrial volume, LV ejection fraction, global longitudinal strain, and myocardial contraction fraction were measured by echocardiography. The participants were divided into LFS or normal flow state (NFS: stroke volume index ≥35 mL/m2). Demographics, clinical and echocardiographic characteristics, and measures of LV remodeling and function were compared between the LFS and NFS groups. Results: The prevalence of LFS was 41%. In comparison with NFS, the LFS had lower LV mass index (77.2±0.96 g/m2 vs 84.6±0.86 g/m2; P<.001), left atrial volume index (20.6±0.35 mL/m2 vs 23.5±0.37 mL/m2; P<.001), global longitudinal strain (-16.8±0.16% vs -17.7±0.17%; P<.001), and myocardial contraction fraction (43.3±0.63% vs 55.7±0.64%; P<.001). There was no significant difference in the relative wall thickness (LFS: 0.40±0.004 vs NFS: 0.40±0.005; P=.57). The LFS group had significantly higher hemoglobin A1c (6.18±0.07% vs 5.97±0.04%; P=.01) than the NFS group. Conclusion: A high prevalence of LFS associated with echocardiographic characteristics reflecting unfavorable LV remodeling and function was observed in a Hispanic/Latino population. Further studies of the prognostic significance of LFS in a large multiethnic population are warranted.

Addition of price transparency to an education and feedback intervention reduces utilization of inpatient echocardiography by resident physicians.

Previous studies have demonstrated the impact of appropriate use criteria (AUC) education and feedback interventions in reducing unnecessary ordering of transthoracic echocardiography (TTE) by trainees. To our knowledge, no study has evaluated the impact of the addition of price transparency to this education and feedback model on TTE utilization by resident physicians. We performed an education and feedback quality improvement initiative combining charge transparency data with information on AUC. We hypothesized that the initiative would reduce the number of complete TTE ordered and increase the number of limited TTE ordered, anticipating there would be substitution of limited for complete studies. Residents rotating on inpatient teaching cardiology ward teams received education on AUC for TTE, indications for limited TTE, and hospital charges for TTE. Feedback was provided on the quantity and charges for complete and limited TTE ordered by each team. We analyzed the effects of the intervention using a linear mixed effects regression model to adjust for potential confounders. The post-intervention weeks showed a reduction of 4.6 complete TTE orders per 100 patients from previous weekly baseline of 31.3 complete TTE orders per 100 patients (p value = 0.012). Charges for complete TTE decreased $122 from baseline of $980 per patient (p value = 0.040) on a per-week basis. Secondarily, there was no statistically significant change in limited TTE ordering during the intervention period. This initiative shows the feasibility of a house staff-driven charge transparency and education/feedback initiative that decreased medical residents' ordering of inpatient TTE.

Discretionary Thrombophilia Test Acquisition and Outcomes in Patients With Venous Thromboembolism in a Real-World Clinical Setting.

Background The value of thrombophilia test acquisition in improving risk prediction beyond clinical presentation remains unknown. We investigated the effect of thrombophilia test acquisition on venous thromboembolism (VTE) outcomes. Methods and Results We performed a retrospective cohort study of adult patients over a 15-year period (September 2001 and May 2016) with first diagnosis of VTE in a single academic medical center. Participants were identified by International Classification of Diseases, Ninth Revision (ICD-9), Current Procedural Terminology (CPT) codes and medication history. Participants with thrombophilia testing were matched to control participants without thrombophilia testing using a propensity model. Primary outcomes included recurrent VTE, anticoagulant use 12 months after the index VTE event, bleeding-related hospitalization, and death. From 3590 unique patients who met the inclusion criteria, 747 participants with VTE who underwent thrombophilia testing were matched to a control participant without testing. Tested participants were more likely to have a recurrent event (46.1% versus 28.5%; P<0.001) and an anticoagulant prescription 12 months from the index event (53.9% versus 37.1%; P<0.001) but had no significant difference in bleeding-related hospitalization (11.4% versus 11.8%; P=0.81) compared with untested participants. An abnormal thrombophilia test result, per se, did not predict recurrent VTE (47.8% versus 44.1%; P=0.13), longer duration anticoagulation (53.2% versus 54.8%; P=0.51), bleeding (11.5% versus 11.3%; P=0.70), or mortality (12.2% versus 16.1%; P=0.18) compared with participants who had normal test results. Conclusions The decision to perform thrombophilia testing, but not the test result, is associated with a high risk of recurrent VTE despite a greater likelihood of long-duration anticoagulation.