Rihal, Charanjit S.

Background Premature coronary artery disease ( CAD ) is common in patients with coarctation of aorta ( COA ), but there are limited data about any direct relationship (or lack thereof) between COA and CAD . We hypothesized that atherosclerotic cardiovascular disease risk factors, rather than COA diagnosis, was the primary determinant of CAD occurrence in patients with COA . Methods and Results This is a retrospective study of 654 COA patients and a control group of 876 patients with valvular pulmonic stenosis and tetralogy of Fallot to determine prevalence and independent risk factors for CAD . There was no evidence of a difference in the unadjusted CAD prevalence between the COA and control groups (7.8% versus 6.3%, P =0.247), but premature CAD was more common in COA patients (4.4% versus 1.8%, P =0.002). In the analysis of a propensity‐matched cohort of 126 COA and 126 control patients, there was no evidence of a difference in overall CAD prevalence (6.3% versus 5.6% versus P =0.742) and premature CAD prevalence (4.8% versus 3.2%, P =0.518). The multivariable risk factors for CAD were hypertension (odds ratio [ OR ] 2.14; 95% CI 1.36–3.38), hyperlipidemia ( OR 3.33; 95% CI 2.02–5.47), diabetes mellitus ( OR 1.98; 95% CI 1.31–3.61), male sex ( OR 2.05; 95% CI 1.33–3.17), and older age per year ( OR 1.06; 95% CI 1.04–1.07). Conclusions After adjusting for atherosclerotic cardiovascular disease risk factors, we did not find evidence of a difference in CAD risk between the patients with COA and other patients with congenital heart disease.

Objective This study aimed to identify characteristics, spectrum of tricuspid regurgitation (TR) severity and treatment patterns in patients considered for intervention of severe TR at a tertiary centre. The population being considered for TR intervention is currently not well defined and the role of transcatheter interventions is unclear. Methods The study involved 87 patients with severe TR considered for intervention from 1 March 2016 to 12 November 2018 at Mayo Clinic. Patients receiving medications alone were compared with those receiving intervention to identify patterns in demographics, clinical/echocardiographic associations and survival. Results Mean age was 80±9 (56% female), 93% had atrial fibrillation and 64% had chronic kidney disease ≥3 a. Follow-up was 331±276 days; 95% were symptomatic with 6 min walk distance of 270±110 m. Loop diuretics were used in 93%; aldosterone antagonists in 35%. Mean tricuspid annular plane systolic excursion was 15.6±3.8 mm, effective regurgitant orifice area (EROA) 82±32 mm2 and stroke volume index 39±11 mL/m2; 48% had at least moderate right ventricular (RV) dysfunction, and 75% did not undergo intervention. Patients receiving intervention showed trends towards larger EROA (93±33 vs 75±31 mm2), better right ventricular function and more severe symptoms. Overall group 30-day and 1-year survival were 100% and 76%, respectively. Conclusions Patients with severe TR considered for intervention are commonly elderly with atrial fibrillation, advanced TR and RV dysfunction; 75% were treated with medications alone and not offered intervention. Patients with greater EROA, better RV function and more severe symptoms were more likely to receive intervention. These findings have implications for future trial design.

Common genetic variation in CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) *2 and *3 alleles leads to a loss of functional protein, and carriers of these loss-of-function alleles when treated with clopidogrel have significantly reduced clopidogrel active metabolite levels and high on-treatment platelet reactivity resulting in increased risk of major adverse cardiovascular events, especially after percutaneous coronary intervention. The Food and Drug Administration has issued a black box warning advising practitioners to consider alternative treatment in CYP2C19 poor metabolizers who might receive clopidogrel and to identify such patients by genotyping. However, routine clinical use of genotyping for CYP2C19 loss-of-function alleles in patients undergoing percutaneous coronary intervention is not recommended by clinical guidelines because of lack of prospective evidence. To address this critical gap, TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention) is a large, pragmatic, randomized trial comparing point-of-care genotype-guided antiplatelet therapy with routine care to determine whether identifying CYP2C19 loss-of-function allele patients prospectively and prescribing alternative antiplatelet therapy is beneficial.

Background: Serum uric acid may serve as a marker of cardiovascular events and outcomes in men, but further studies are required to determine its role in women. We aimed to determine differences in procedural characteristics and outcomes in women undergoing percutaneous coronary intervention(PCI). Methods: We retrospectively analyzed the Mayo Clinic Cardiovascular Catheterization Laboratory database, and included patients undergoing PCI from 1/1/2000 to 12/31/2007. There were 495 women who underwent PCI in this time period. Patients were divided into normal uric acid (n=240) and high uric acid (n=255) groups, and high uric acid was defined as >6.0 mg/dL. Patients were followed for adverse outcomes for a median of 47.1 (IQR 23.8, 62.8) months. Results: Mean age was 66.6 + 12.7 years in the normal group vs. 70.5 + 11.2 years in the elevated uric acid group(p=0.01). Hypertension and diabetes were more prevalent in the elevated uric acid group (p<0.01). BMI was significantly higher in the elevated uric acid group (p=0.001). There was a higher prevalence of calcified lesions among women with elevated uric acid when compared to those with normal uric acid levels (47% vs. 30% p<0.001). There was significantly lower TIMI=3 flow postprocedurally in those with elevated uric acid levels when compared to those with normal uric acid levels (91 % vs. 97%, p=0.003). After adjusting for potential confounders including age, hyperlipidemia, hypertension, BMI, diabetes, and chronic kidney disease, elevated uric acid was associated with increased likelihood of death (HR 1.8, p=0.01) and the composite endpoint of death or subsequent myocardial infarction (HR 1.5, p=0.03). Discussion: Uric acid may be an independent determinant of procedural characteristics and a predictor of outcomes after percutaneous intervention. Further studies are required to better understand the effect of uric acid on cardiovascular events in women.

AbstractObjectiveTo understand the clinical and hemodynamic response of patients with stenotic versus regurgitant prosthetic mitral valve degeneration to transseptal transcatheter mitral valve‐in‐ring/‐valve replacement (TMVR).BackgroundPatients with prosthetic mitral valve repair/replacement failure frequently present high‐risk surgical challenges. TMVR has been employed as an alternative to surgery.MethodsForty‐four patients with stenotic/regurgitant degeneration of prior prosthetic mitral annuloplasty and replacement (38) underwent mitral TMVR. Clinical, echocardiographic, and invasive hemodynamic monitoring was conducted at baseline and follow‐up.ResultsRelative to patients with regurgitant degeneration (28), patients with stenotic degeneration had baseline higher mitral valve gradients (12 ± 4 vs. 7 ± 3 mmHg, p < 0.01) and smaller areas (1.0 ± 0.4 vs. 1.5 ± 0.4 cm2, p = 0.01). TMVR yielded significant reduction in left atrial v‐wave pressures in stenotic and regurgitant cohorts (−7 ± 11, p = 0.03, and −11 ± 12 mmHg, p < 0.01, respectively) and significant, sustained symptomatic improvement. Intracardiac pressures overall, including left ventricular end diastolic pressures, remained elevated.ConclusionDespite baseline differences in valvular disease, TMVR leads to significant hemodynamic and clinical improvement in both stenotic and regurgitant prosthetic mitral valve disease. In both cohorts, TMVR reduced intracardiac pressures to similar postprocedural levels, but pressures remained supranormal. This outcome suggests a multifactorial process defines the pathophysiology of patients undergoing TMVR, including contributions from prosthetic degeneration, changes in left atrial compliance, and diastolic dysfunction, and highlights the need to consider such factors in patient evaluation and treatment.

AbstractLeft ventricular pseudoaneurysm is an infrequent but potentially fatal complication following cardiac surgery, with spontaneous rupture being the most feared result. Moreover, surgical repair is associated with significant morbidity and mortality. We present a successful transapical percutaneous closure of a post‐surgical rapidly expanding left ventricular outflow tract (LVOT) pseudoaneurysm utilizing Amplatz Vascular Plug‐II (AVP‐II) (St. Jude Medical, St. Paul, MN) with the aid of 3D prototyping for pre‐procedural planning.

AbstractBackgroundTreatment of hemodynamically significant mitral annular calcification (MAC) using transcatheter approaches is in the early learning phase. The occurrence of paravalvular leak (PVL) following transcatheter mitral valve in MAC is common.AimsTo report the initial experience and techniques of percutaneous PVL closure after transcatheter valve in MAC.MethodsThis series includes five consecutive patients who underwent percutaneous PVL closure following transcatheter balloon expandable SAPIEN S3 valve in MAC.ResultsMean patient age was 73.6 ± 5.4 years (4 [80%] female), with average Society of Thoracic Surgeons score of 8.1 ± 2.8%. Three patients had a single PVL defect while two patients had two defects; all were located at the commissural sites. Closure was performed primarily for heart failure in four patients and hemolytic anemia in one patient. Transfemoral transseptal antegrade approach and Amplatz Vascular Plug (AVP)‐II occluders were utilized in all patients. Procedure success was achieved in three patients. One patient developed significant occluder related leaflet impingement and subsequent severe prosthetic mitral regurgitation requiring a second transcatheter mitral valve in valve implantation. The procedure was aborted in one patient due to difficulty crossing PVL defect after balloon post‐dilatation of SAPIEN prosthesis with 10 mL of additional volume. There was no in hospital or 30 day mortality or the need for emergent surgery.ConclusionEarly experience with percutaneous PVL closure of SAPIEN valve in MAC demonstrated feasibility of this approach. Careful procedure planning and monitoring for SAPIEN prosthesis leaflet impingement and frame instability is of utmost importance to increase the chances of procedural success.

Aim Angina pectoris in the absence of obstructive coronary artery disease (CAD) is common and is associated with poor quality of life (QOL). Coronary microvascular endothelial dysfunction is associated with myocardial ischaemia and is a common cause of angina. We hypothesise that evaluation of coronary endothelial function, its diagnosis and treatment will favourably impact QOL in patients with angina symptoms and non-obstructive CAD. Methods and results Follow-up was done on 457 patients with chest pain and non-obstructive coronary arteries who had undergone coronary vascular reactivity evaluation by administration of intracoronary acetylcholine at the time of diagnostic study. After a mean follow-up of 8.4±4.7 years, QOL was assessed by administration of the SF-36 QOL survey. Patients diagnosed and treated for microvascular endothelial dysfunction had a higher (better) overall mental composite score (44.8 vs 40.9, p=0.036) and mental health score (44.2 vs 40.7, p=0.047), and a trend towards higher vitality scores (39.1 vs 35.9, p=0.053) and role emotional scores (43.6 vs 40.4, p=0.073), compared with patients with normal endothelial function. Conclusion Among patients with chest pain and normal coronaries, diagnosis and treatment of coronary microvascular endothelial dysfunction in those with angina pectoris and non-obstructive CAD are associated with better QOL compared with patients with normal endothelial function.

AbstractBackgroundThe effect of utilizing transapical (TA) access for transcatheter aortic valve replacement (TAVR) on cardiac function has not been well studied.AimsThe aim of this retrospective study is to determine the direct effects of TA access for TAVR on myocardial function parameters and their correlation with 4‐year survival.MethodsThree hundred and thirty propensity matched patients, who underwent TAVR using Sapien valve (Edwards Lifesciences Corp, Irvine, CA) between February 15, 2012 and June 17, 2016 (115 TA and 115 transfemoral [TF] routes) were studied. The pre‐ and 1 month post‐TAVR echocardiographic features of both groups were compared. The 4‐year survival in both groups was analyzed.ResultsBaseline clinical characteristics, diastolic function parameters, left ventricular (LV) chamber size, and ejection fraction were similar between matched TA and TF groups. At 1 month following TAVR, there was a significant increase in stroke volume index (SVI) in both TA (mean increase 7 cm3/m2; P = 0.03) and TF groups (mean increase 7 cm3/m2; P < 0.001). Left ventricular ejection fraction (LVEF) significantly increased post TF TAVR (mean increase 2%; P = 0.008), but no significant increase was observed post TA TAVR (mean increase 1%; P = 0.27). Both groups had significant improvement in aortic valve (AV) hemodynamics post‐TAVR (P < 0.001). Overall, there were no significant differences in the mean change of SVI, LVEF, or left ventricular end diastolic dimensions (LVEDDs) post TA versus TF TAVR. There was no significant difference in 4‐year survival in the TF compared to TA group (49% vs 50%, P = 0.43).ConclusionBoth TA and TF TAVR were equally associated with favorable changes in LV SVI and AV hemodynamics in 30 days. TA TAVR patients had similar 4 year survival to propensity matched TF TAVR; therefore, TA TAVR remains an acceptable alternative access route in patients not amenable to TF TAVR.