Transcatheter Aortic Valve Replacement in a Young Patient With Mandibuloacral Dysplasia.

A young woman with mandibuloacral dysplasia, a syndrome on the progeria spectrum with accelerated vascular calcification and calcific valve stenosis, presented with symptomatic severe aortic stenosis. She underwent transcatheter aortic valve replacement with a balloon-expandable valve, and her exertional symptoms improved significantly. (Level of Difficulty: Intermediate.).

Clinical Significance of Greater Implantation Height with SAPIEN 3 Transcatheter Heart Valve.

BACKGROUND: A lower rate of permanent pacemaker (PPM) has been linked to a target aortic implantation height (AIH) >0.70, following transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve. Based on clinical experience, it was hypothesized that a higher AIH (≥0.85) would lower the rate of PPM implantation. METHODS: A total of 127 patients (66 females, 61 males; mean age 82 ± 8 years) underwent TAVR with the SAPIEN 3 valve between May 2015 and July 2016. AIH was defined as the proportion of the valve frame above the aortic annulus in the post-deployment aortogram. A target AIH (≥0.70) was achieved in 113 patients (89%). Cases were stratified into a High Implantation (HI) group (AIH ≥0.85; 33 patients) or a Standard Implantation (SI) group (AIH <0.85; 94 patients). RESULTS: The mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score of all patients was 6.4 ± 3.5%. Preoperative right bundle branch block (RBBB) was prevalent in 13% of SI patients, and in 18% of HI patients (p = 0.56). There were no significant differences in operative mortality (3.2% versus 0%), median length of stay (2 days versus 3 days) and incidence of moderate-to-severe paravalvular leak (3.2% versus 0%; all p >0.410) between SI and HI patients, respectively. Likewise, the incidence of new PPM did not differ between the two groups (12% in HI versus 13% in SI; p ≥0.99). The mean AIH was similar for patients with PPM implantation (0.80 ± 0.08) compared to those without (0.78 ± 0.06; p = 0.520). Preoperative RBBB was significantly associated with PPM implantation (odds ratio (OR) 10.1; p = 0.002), and patients who underwent PPM implantation had a higher operative mortality (12.5% versus 1%; p = 0.040). CONCLUSIONS: Among TAVR patients who received the SAPIEN 3 heart valve, a higher AIH (≥0.85) was not associated with a lower rate of PPM implantation or increased operative mortality. Prior RBBB was the only independent risk factor for new PPM implantation. Long-term follow up is crucial in determining the clinical significance of PPM implantation.

Impact of flow, gradient, and left ventricular function on outcomes after transcatheter aortic valve replacement.

OBJECTIVES: To assess the impact of low flow with and without preserved left ventricular ejection fraction (LVEF) on outcomes after transcatheter aortic valve replacement (TAVR). BACKGROUND: Prior studies have shown that patients with low flow, AVG, and LVEF have worse outcomes after TAVR. It is unclear whether low AVG and LVEF remain prognostic after adjusting for flow, and how the outcomes of patients with low flow with and without preserved LVEF compare after TAVR. The goal of this study was to provide insight into these open questions. METHODS: Data from 340 TAVR patients at Brigham and Women's Hospital from 2011 through 2015 were analyzed. Low flow was defined as stroke volume index (SVI) ≤35 mL/m2 , low AVG as mean gradient < 40 mmHg, and reduced LVEF as < 50%. RESULTS: Low flow was present in 96 (28.2%) patients, 48 (50.0%) of whom also had reduced LVEF. At 1 year, low flow was associated with increased mortality (21.9 vs 7.4%; P = 0.0002) and heart failure (HF) (20.8 vs 5.3%; P = 0.0113). Among patients with low flow, those with preserved LVEF had increased mortality (HR 5.17, 95% CI 2.73-9.80; P < 0.001) and HF (HR 7.69, 95% CI 3.86-15.31; P < 0.001). After adjusting for clinical factors, patients with low flow had increased mortality (HR 6.51, 95% CI 2.98-14.22; P < 0.001) and HF (HR 5.52, 95% CI 2.34-12.98; P < 0.001), while neither low AVG nor low LVEF were associated with increases in mortality or HF. CONCLUSIONS: In patients undergoing TAVR, low flow was an independent predictor of 1-year mortality and HF, and a stronger predictor than either low AVG or LVEF. Patients with low flow and preserved EF had increased mortality and HF at 1-year, while those with low flow and reduced EF had outcomes similar to patients with normal flow.

A heart within a heart.

A 44-year-old man with a history of end-stage dilated cardiomyopathy status-post orthotopic cardiac transplant 14 years ago presented for coronary angiography in preparation for re-operative tricuspid valve replacement. Coronary angiography revealed an anomalous origin of the left coronary artery, with a common coronary trunk arising from the right coronary cusp and bifurcating into right and left main coronary arteries. Interestingly, the right and left coronary arteries coursed to form the shape of a heart, hence, a heart within a heart! © 2017 Wiley Periodicals, Inc.

Diabetes mellitus, CYP2C19 genotype, and response to escalating doses of clopidogrel. Insights from the ELEVATE-TIMI 56 Trial.

Both diabetes mellitus (DM) and carriage of the CYP2C19*2 allele are associated with a reduced response to clopidogrel. The relative contributions of these factors and whether higher clopidogrel doses can overcome both factors remain unknown. The objective of this study was to test the ability of clopidogrel doses up to 300 mg daily to decrease platelet reactivity in patients with DM and/or CYP2C19*2. ELEVATE-TIMI 56 randomised 333 patients with coronary artery disease to different maintenance doses of clopidogrel in four treatment periods, each lasting approximately 14 days. On-treatment platelet reactivity was compared between patients stratified by DM, CYP2C19*2 status and clopidogrel dose. Both DM and CYP2C19*2 were independently associated with elevated on-treatment platelet reactivity with clopidogrel 75 mg daily (p<0.0001 for each). With 75 mg, mean on-treatment PRU was progressively higher (p trend <0.001) when evaluating patients: with neither DM nor CYP2C19*2 (150.7; 95 % CI 140.5-162.6), with only DM (187.2; 95 % CI, 171.3-206.9), with only CYP2C19*2 (227.9; 95 % CI, 205.1-250.8), and with both DM and CYP2C19*2 (239.9; 95 % CI, 209.7-270.1). Notably, with 75 mg, patients with only CYP2C19*2 had higher on-treatment platelet reactivity than those with only DM (p=0.0068). To achieve on-treatment platelet reactivity similar to that seen with clopidogrel 75 mg in patients with neither DM nor CYP2C19*2, the following doses were required: 150 mg with only DM, 225 mg with only CYP2C19*2, and 300 mg with both DM and CYP2C19*2. Patients with both DM and CYP2C19*2 required a four-fold increase in clopidogrel maintenance dose as compared to patients without these factors to achieve a similar antiplatelet response.

Role of oral anticoagulants in patients after an acute coronary syndrome.

After an acute coronary syndrome, patients continue to be at risk of adverse cardiovascular events despite treatment with the current standard of antithrombotic therapy. The risk may be in part secondary to thrombin, which remains elevated after an acute coronary syndrome event. Several studies have investigated the utility of adding oral anticoagulation to post-acute coronary syndrome medical regimens, with the most promising results coming from the addition of low-dose oral direct anticoagulants. Focusing on optimal dosing strategies and applying therapies to the appropriate populations provide the ability to maximize benefit and minimize risk.

Balancing antiplatelet and anticoagulant therapies in patients with cardiovascular disease.

Anticoagulation is needed for stroke prevention in patients with atrial fibrillation. Antiplatelet therapy is essential for the prevention of stent thrombosis and the reduction of cardiovascular events in patients who undergo coronary stenting and suffer acute coronary syndromes. When these conditions overlap, the individual antithrombotic strategies are commonly combined, and the efficacy benefit of triple oral antithrombotic therapy is assumed to outweigh the bleeding risk based on the available data. Recent studies have investigated this topic further, including the first randomized controlled trial to address this issue. This new evidence challenges previous assumptions and may have implications for future practice and investigation.

Antithrombotic therapy: triple therapy or triple threat?

Antithrombotic therapy plays an essential role in the management of some of the most common and morbid medical conditions. Triple oral antithrombotic therapy (TOAT) is defined as the administration of both therapeutic oral anticoagulation (OAC) and dual antiplatelet therapy (DAPT) to patients with indications for both treatments. The current societal guidelines regarding TOAT are derived from observational studies and some trials of the use of warfarin in addition to antiplatelet therapy in patients with atrial fibrillation and a recent acute coronary syndrome or percutaneous coronary intervention. The general apprehension to administer TOAT is due to the heightened concern for bleeding, rendering warfarin's pharmacokinetic properties concerning. Newer anticoagulant agents may serve as appealing alternatives, and further investigations are warranted. The results of the recent trials that have studied the use of these agents in atrial fibrillation and acute coronary syndrome offer some useful applications to TOAT. Ultimately, selecting the most favorable antithrombotic strategy is going to involve weighing the risks and benefits for each patient.