Ethnic and Gender Disparities in the Uptake of Transcatheter Aortic Valve Replacement in the United States Abstract Introduction Little is known about ethnic and gender disparities for transcatheter aortic valve replacement (TAVR) procedures in the United States. Methods We queried the Nationwide Inpatient Sample (NIS) database (2011–2014) to identify patients who underwent TAVR. We described the temporal trends in the uptake of TAVR procedures among various ethnicities and genders. Results Our analysis identified 39,253 records; 20,497 (52.2%) were men and 18,756 (47.8%) were women. Among all TAVRs, 87.2% were Caucasians, 3.9% were African Americans (AA), 3.7% were Hispanics, and 5.2% were of other ethnicities. We found a significant rise in the trend of TAVRs in all groups: in Caucasian men (coefficient = 0.946, p < 0.001), Caucasian women (coefficient = 0.985, p < 0.001), AA men (coefficient = 0.940, p < 0.001), AA women (coefficient = 0.864, p < 0.001), Hispanic men (coefficient = 0.812, p = 0.001), Hispanic women (coefficient = 0.845, p < 0.001). Hence, the uptrend was most significant among Caucasian women, and relatively least significant among Hispanic men. Multivariate regression analysis was conducted to evaluate in-hospital mortality among different groups after adjusting for demographics and baseline characteristics. After multivariable regression for baseline characteristics overall, the in-hospital mortality per 100 TAVRs was highest among Hispanic men 5.5%, followed by Caucasian women 5.0%, Hispanic women 4.6%, AA women 3.7%, AA men 3.4%, and Caucasian men 3.38% (adjusted p value = 0.004). Conclusions In this observational study, we demonstrated that there is evidence of ethnic and gender differences in the overall uptake and adjusted mortality of TAVRs in the United States.

Current Evidence on Oral Antibiotics for Infective Endocarditis: A Narrative Review Abstract Infective endocarditis (IE) continues to be associated with high morbidity and mortality, even when treated with optimal antibiotic regimens. The selection of treatment depends on the causative pathogen, its antibiotic susceptibility profile, local and systemic complications and the presence of prosthetic materials or devices. Standard therapy typically involves 4–6 weeks of intravenous (IV) bactericidal therapy. However, there are instances in which IV antibiotic administration may be challenging due to cost, complications of IV access, adverse side-effects of the medication or concerns for misuse of the IV line. Current clinical guidance from the American Heart Association and the European Society of Cardiology cite scenarios where oral antibiotics can be considered for treatment of IE, though these situations are relatively infrequent and data to show their non-inferiority limited. Recently, a well-designed randomized clinical study reported favorable outcomes for partial oral antimicrobial therapy regimens given to patients with staphylococcal, streptococcal and enterococcal IE deemed clinically stable and without complications such as perivalvular abscess. Oral antibiotics, usually given in combination, were selected by infectious disease providers for their favorable pharmacologic properties and predicted bactericidal activity. There was a careful selection of patients who were transitioned to oral regimens. Before recommending routine use of oral antibiotics in the care of patients with IE, additional studies that better define eligible patients and that use regimens available in the countries that adopt this practice should be performed. If further studies confirm non-inferior outcomes with partial oral antibiotics for the treatment of IE, medical treatment could be delivered in a simpler, more costeffective manner, and likely with lower rates of adverse side-effects.

A Review of the Role of Bradykinin and Nitric Oxide in the Cardioprotective Action of Angiotensin-Converting Enzyme Inhibitors: Focus on Perindopril Abstract The functional integrity of the endothelium is essential for vascular health. In addition to maintaining a delicate balance between vasodilation and vasoconstriction, the endothelium has numerous other complex roles involved in the maintenance of vascular homeostasis. Chronic exposure to cardiovascular risk factors and oxidative stress results in an imbalance in these functions, creating an environment that favors reduced vasodilation and a proinflammatory and prothrombic state. The involvement of endothelial dysfunction in all stages of the cardiovascular continuum makes it an important target for treatment. One of the major endothelial-derived factors involved in the maintenance of endothelial function is nitric oxide (NO). Angiotensin-converting enzyme (ACE) inhibitors increase NO production both directly and indirectly by preventing production of angiotensin II (which diminishes NO production) and inhibiting the degradation of bradykinin (which stimulates local release of NO). Among the ACE inhibitors, perindopril appears to have the greatest effects on bradykinin and has demonstrated efficacy in a number of markers of endothelial dysfunction including arterial stiffness and progression of atherosclerosis. There is also strong evidence supporting the use of perindopril-based therapy for the treatment of hypertension and for reducing the risk of cardiovascular morbidity and mortality in a wide range of patients across the cardiovascular continuum. Funding: The journal’s Rapid Service Fee was funded by Servier.

Estimating the Prevalence of Transthyretin Amyloid Cardiomyopathy in a Large In-Hospital Database in Japan Abstract Introduction Transthyretin amyloid cardiomyopathy (ATTR-CM)—a debilitating, fatal disease resulting from the deposition of transthyretin (TTR) amyloid fibrils—can be hereditary due to mutations in the TTR gene (ATTRm) or wild type (ATTRwt). The global prevalence of ATTR-CM is largely unknown, although likely underestimated, with no formal epidemiological prevalence studies in Japan. This study aimed to estimate the prevalence of ATTR-CM in a large in-hospital database in Japan. Methods This was a retrospective, observational, cross-sectional study which utilized data from all adult patients (aged ≥ 20 years) in the hospital-based Japan Medical Data Vision (MDV) database from January 2010 to September 2018 to estimate the number of currently diagnosed ATTR-CM patients and describe their demographic and clinical characteristics and diagnostic modalities. ATTR-CM patients (ATTRwt and ATTRm) were identified using a range of diagnosis codes that were applied to create broad and narrow definitions of the disease. Results Over the 9 years of this study, there were 3255 (155.8 per million adult patients in the MDV database) to 3992 (191.1 per million) diagnoses of ATTRwt and 67 (3.2 per million) to 106 (5.1 per million) diagnoses of ATTRm in the MDV database (based on the narrow and broad definitions, respectively). There were 444 (21.2 per million) diagnoses of amyloid light-chain (AL) amyloidosis. Considering only those patients who were also diagnosed with heart failure, there were 1468 (70.3 per million) to 1798 (86.1 per million) diagnoses of ATTRwt and 50 (2.4 per million) to 61 (2.9 per million) diagnoses of ATTRm. Most ATTRwt patients (~ 90%) did not have a record of endomyocardial or abdominal wall biopsy, or of scintigram. Conclusion This retrospective study provides an estimate of the number of patients diagnosed with ATTR-CM in a large in-hospital database in Japan over a period of 9 years. Improving awareness of disease prevalence may improve diagnosis and treatment. Funding Pfizer.

Patient-Reported Satisfaction and Study Drug Discontinuation: Post-Hoc Analysis of Findings from ROCKET AF Abstract Introduction Patient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation. Methods ROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up). Results A total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation. Conclusions Study drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. ClinicalTrials.gov NCT00403767. Funding The ROCKET AF trial was funded by Johnson & Johnson and Bayer.

A Review of Antithrombotic Treatment in Critical Limb Ischemia After Endovascular Intervention Abstract Endovascular intervention is often used to treat critical limb ischemia (CLI). Post-intervention treatment with antiplatelet and/or anticoagulant therapy has reduced morbidity and mortality due to cardiovascular complications. The purpose of this review is to shed light on the various pharmacologic treatment protocols for treating CLI following endovascular procedures. We reviewed the literature comparing outcomes after antithrombotic treatment for patients with CLI. We characterized antithrombotic therapies into three categories: (1) mono-antiplatelet therapy (MAPT) vs. dual antiplatelet therapy (DAPT), (2) MAPT vs. antiplatelet (AP) + anticoagulant (AC) therapy, and (3) AC vs. AP + AC therapy. Relevant results and statistics were extracted to determine differences in the rates of the following outcomes: (1) re-stenosis, (2) occlusion, (3) target limb revascularization (TLR), (4) major amputation, (5) major adverse cardiac events, (6) all-cause death, and (7) bleeding. Studies suggest that DAPT reduces post-surgical restenosis, TLR, and amputation for diabetic patients, without increasing major bleeding incidences, compared to MAPT. Also, AP + AC therapy provides overall superior efficacy, with no difference in bleeding incidences, compared to antiplatelet alone. Additionally, the effects were significant for restenosis, limb salvage, survival rates, and cumulative rate of above ankle amputation or death. These results suggest that treatment with DAPT and AP + AC might provide better outcomes than MAPT following the endovascular intervention for CLI, and that the ideal treatment may be related to the condition of the individual patient. However, the studies were few and heterogenous with small patient populations. Therefore, further large controlled studies are warranted to confirm these outcomes.

Insulin Resistance is Associated with Longitudinal Changes of Cardiac Repolarization Heterogeneity in Apparently Healthy Subjects Abstract Introduction Increased heterogeneity in ventricular repolarization is a risk factor of sudden cardiac death, but its natural history is unclear. Here we examined whether insulin resistance is associated with longitudinal change in ventricular repolarization heterogeneity in apparently healthy subjects. Methods The study subjects were participants in health checkups in cohort 1 and cohort 2, which were followed up for 6 years and 5 years, respectively. Subjects with diabetes, cardiovascular disease, or renal disease at baseline were excluded from the analyses. As indices of insulin resistance, the homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride to HDL-cholesterol ratio (TG/HDL-C) were used in cohort 1 and cohort 2, respectively. Heterogeneity in ventricular repolarization was assessed by heart rate-corrected Tpeak–Tend interval in V5 (cTpTe), QT interval, and QT dispersion. In regression analyses, parameters with a skewed distribution were normalized by logarithmic transformation or by Box–Cox transformation. Results In longitudinal analyses, Box–Cox-transformed cTpTe at the end of follow-up was weakly correlated with log HOMA-IR at baseline in cohort 1 (n = 153, r = − 0.207, 95% CI − 0.354 to − 0.050, p = 0.010) and with log TG/HDL-C at baseline in cohort 2 (n = 738, r = − 0.098, 95% CI − 0.169 to − 0.026, p = 0.008). Multiple regression analysis showed that indices of insulin resistance, but not glycosylated hemoglobin (HbA1c) or plasma glucose, at baseline were significant explanatory variables for cTpTe at the end of follow-up. Neither QT interval nor QT dispersion was correlated with metabolic parameters. Conclusion Insulin resistance may be involved in the longitudinal increase of ventricular repolarization heterogeneity in apparently healthy subjects.

Losartan for Preventing Aortic Root Dilatation in Patients with Marfan Syndrome: A Meta-Analysis of Randomized Trials Abstract Introduction The role of losartan in preventing aortic root dilatation in Marfan syndrome has been evaluated in many clinical trials; however, the results are conflicting. Methods We performed a computerized search of MEDLINE, EMBASE and COCHRANE databases through February 2019 for randomized clinical trials evaluating the effect of losartan in patients with Marfan syndrome. The main outcome was the change in the aortic root diameter in the losartan versus control groups. Results Our final analysis included seven randomized trials with a total of 1352 patients and average weighted follow-up of 37.8 months. Change in aortic root diameter was significantly smaller with losartan compared with control [weighted means: 0.44 vs. 0.58 mm, mean difference (MD) = −0.13; 95% CI −0.24 to −0.02; p = 0.02]. Subgroup analysis according to the control group showed no significant subgroup interaction when comparing losartan with beta-blockers versus with standard therapy (pinteraction= 0.27). The composite outcome of aortic surgery, dissection or mortality did not differ between the losartan and control groups (risk ratio = 1.03; 95% CI 0.72–1.49, p = 0.86). Conclusion In this meta-analysis including seven randomized trials, the use of losartan was associated with a significantly smaller change in aortic root diameter in patients with Marfan syndrome.

Acute and Long-Term Outcomes of Patients with Impaired Left Ventricular Systolic Function Undergoing Rotational Atherectomy: A Single-Center Observational Retrospective Study Abstract Introduction Rotational atherectomy (RA) historically was contraindicated in patients with impaired left ventricular (LV) function due to inherent cardio-depressive effects. Contemporary RA practice is less aggressive than traditional RA and no longer withheld from patients with reduced ejection fraction (EF). The aim of this analysis is to explore the outcomes of rotational atherectomy (RA) in patients with reduced left ventricular ejection fraction (LVEF). Methods Patients undergoing RA (n = 644) were divided into three groups according to LVEF (severely reduced ≤ 35%, n = 82; moderately reduced 36–54%, n = 170; and preserved LVEF ≥ 55%, n = 392). Results Compared to patients with preserved LVEF, those with severely reduced LVEF had higher rates of angiographic failure (12.2 vs. 3.3%, p = 0.003) and in-hospital major adverse cardiac events (MACE: 9.8 vs. 2.3%, p = 0.004) driven by more peri-procedural myocardial infarction (MI: 6.1 vs. 1.5%, p = 0.049). In-hospital outcomes were similar between patients with preserved and moderately reduced LVEF. At 5-year follow-up, a stepwise increase in all-cause death was observed with lower LVEF (preserved: 15%, moderately reduced: 23%, severely reduced: 43%; p < 0.001). On the other hand, revascularization and MI rates at 5 years were not affected by LVEF. Conclusions Compared to patients with preserved LVEF, those with severely reduced LVEF have worse acute outcomes after RA, whereas a moderate reduction of LVEF poses no additional acute hazard after RA. Up to 5 years, the extent of left ventricular dysfunction was associated with a stepwise increase in mortality.

TRimetazidine as an Agent to affeCt clopidogrEl Response: The TRACER Study Abstract Introduction This prospective study aimed to determine whether trimetazidine (TMZ) alters the pharmacodynamic (PD) effects of clopidogrel. Methods Patients with stable coronary artery disease (SCAD) (n = 24) who were actively treated with dual antiplatelet therapy (DAPT) of aspirin 81 mg daily and clopidogrel 75 mg daily were recruited. Platelet function was measured with the VerifyNow P2Y12 assay (Accriva Diagnostics, San Diego, CA, USA) and assessed before the initiation of and after 14 days of treatment with TMZ. Results were compared using a paired t test. Results Almost 80% of the study population were of South Asian descent and had diabetes mellitus (DM). P2Y12 reaction units (PRUs) were higher in patients on TMZ (204 ± 56 compared with 174 ± 71 before TMZ, p = 0.005). The average increase in PRU score was 29 (95% confidence interval 8.8–49.7). Before TMZ, the proportion of patients with high on-treatment platelet reactivity (PRU > 208 units) was 25%, which increased to 42% for patients on TMZ. Conclusion Higher platelet reactivity was seen in patients on TMZ, suggesting that TMZ attenuated the PD effects of clopidogrel in this study of a predominantly South Asian diabetic subpopulation. Alternative therapies should be considered and further research is warranted. Trial Registration ClinicalTrials.gov number, NCT03603249.