Left atrial to coronary sinus shunting for treatment of heart failure with mildly reduced or preserved ejection fraction: The ALT FLOW Early Feasibility Study 1-year results.

AIMS: Patients with heart failure and mildly reduced or preserved ejection fraction have limited therapeutic options. The ALT-FLOW Early Feasibility Study evaluated safety, haemodynamics and outcomes for the APTURE transcatheter shunt system, a novel left atrium to coronary sinus shunt in these patients. METHODS AND RESULTS: Safety and shunt implantation success was evaluated for all 116 enrolled patients. An analysis population of implanted patients with a left ventricular ejection fraction (LVEF) >40% (n = 95) was chosen to assess efficacy via paired comparison between baseline and follow-up haemodynamic (3 and 6 months), and echocardiographic, clinical and functional outcomes (6 months and 1 year). Health status and quality of life outcomes were assessed using the Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS). The primary safety endpoint, major adverse cardiac, cerebral, and renal events, and reintervention through 30 days, occurred in 3/116 patients (2.6%). All implanted shunts were patent at 1 year. In patients with LVEF >40%, the mean (95% confidence interval) reduction in exercise pulmonary capillary wedge pressure (PCWP) at 20 W was -5.7 (-8.6, -2.9) mmHg at 6 months (p < 0.001). At baseline, 8% had New York Heart Association class I-II status and improved to 68% at 1 year (p < 0.001). KCCQ-OSS at baseline was 39 (35, 43) and improved at 6 months and 1 year by 25 (20-30) and 27 (22-32) points, respectively (both p < 0.0001). No adverse changes in haemodynamic and echocardiographic indices of right heart function were observed at 1 year. Overall, the reduction in PCWP at 20 W and improvement in KCCQ-OSS in multiple subgroups were consistent with those observed for the entire population. CONCLUSIONS: In patients with heart failure and LVEF >40%, the APTURE shunt demonstrated an acceptable safety profile with significant sustained improvements in haemodynamic and patient-centred outcomes, underscoring the need for further evaluation of the APTURE shunt in a randomized trial.

Transcarotid versus transaxillary access for transcatheter aortic valve replacement with a self-expanding valve: A propensity-matched analysis.

Transaxillary access has been the most frequently used nonfemoral access route for transcatheter aortic valve replacement (TAVR) with a self-expanding valve. Use of transcarotid TAVR is increasing; however, comparative data on these methods are limited. We compared outcomes following transcarotid or transaxillary TAVR with a self-expanding, supra-annular valve. Methods: The Transcatheter Valve Therapy Registry was queried for TAVR procedures using transaxillary and transcarotid access between July 2015 and June 2021. Patients received a self-expanding Evolut R, PRO, or PRO + valve (Medtronic) and had 1-year follow-up. Thirty-day and 1-year outcomes were compared in transcarotid and transaxillary groups after 1:2 propensity score-matching. Multivariable regression models were fitted to identify predictors of key end points. Results: The propensity score-matched cohort included 576 patients receiving transcarotid and 1142 receiving transaxillary access. Median procedure time (99 vs 118 minutes; P < .001) and hospital stay (2 vs 3 days; P < .001) were shorter with transcarotid versus transaxillary access. At 30 days, patients with transcarotid access had similar mortality (Kaplan-Meier estimates 3.7% vs 4.3%, P = .57) but significantly lower stroke (3.1% vs 5.9%; P = .017) and mortality or stroke (6.0% vs 8.9%; P = .033) compared with patients receiving transaxillary access. Similar differences were observed at 1 year. Transaxillary access was associated with increased risk of 30-day stroke (hazard ratio, 2.14; 95% confidence interval, 1.27-3.58) by multivariable regression analysis. Conclusions: Transcarotid versus transaxillary access for TAVR using a self-expanding valve is associated with procedural benefits and significantly lower stroke and mortality or stroke at 30 days. In patients with unsuitable femoral anatomy, transcarotid access may be the preferred delivery route for self-expanding valves.

Transcatheter Repair for Patients with Tricuspid Regurgitation.

BACKGROUND: Severe tricuspid regurgitation is a debilitating condition that is associated with substantial morbidity and often with poor quality of life. Decreasing tricuspid regurgitation may reduce symptoms and improve clinical outcomes in patients with this disease. METHODS: We conducted a prospective randomized trial of percutaneous tricuspid transcatheter edge-to-edge repair (TEER) for severe tricuspid regurgitation. Patients with symptomatic severe tricuspid regurgitation were enrolled at 65 centers in the United States, Canada, and Europe and were randomly assigned in a 1:1 ratio to receive either TEER or medical therapy (control). The primary end point was a hierarchical composite that included death from any cause or tricuspid-valve surgery; hospitalization for heart failure; and an improvement in quality of life as measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ), with an improvement defined as an increase of at least 15 points in the KCCQ score (range, 0 to 100, with higher scores indicating better quality of life) at the 1-year follow-up. The severity of tricuspid regurgitation and safety were also assessed. RESULTS: A total of 350 patients were enrolled; 175 were assigned to each group. The mean age of the patients was 78 years, and 54.9% were women. The results for the primary end point favored the TEER group (win ratio, 1.48; 95% confidence interval, 1.06 to 2.13; P = 0.02). The incidence of death or tricuspid-valve surgery and the rate of hospitalization for heart failure did not appear to differ between the groups. The KCCQ quality-of-life score changed by a mean (±SD) of 12.3±1.8 points in the TEER group, as compared with 0.6±1.8 points in the control group (P<0.001). At 30 days, 87.0% of the patients in the TEER group and 4.8% of those in the control group had tricuspid regurgitation of no greater than moderate severity (P<0.001). TEER was found to be safe; 98.3% of the patients who underwent the procedure were free from major adverse events at 30 days. CONCLUSIONS: Tricuspid TEER was safe for patients with severe tricuspid regurgitation, reduced the severity of tricuspid regurgitation, and was associated with an improvement in quality of life. (Funded by Abbott; TRILUMINATE Pivotal ClinicalTrials.gov number, NCT03904147.).

Invasive assessment of myocardial bridging in patients with angina and no obstructive coronary artery disease.

AIMS: Angina and no obstructive coronary artery disease (ANOCA) is common. A potential cause of angina in this patient population is a myocardial bridge (MB). We aimed to study the anatomical and haemodynamic characteristics of an MB in patients with ANOCA. METHODS AND RESULTS: Using intravascular ultrasound (IVUS), we identified 184 MBs in 154 patients. We evaluated MB length, arterial compression, and halo thickness. MB muscle index (MMI) was defined as MB length×halo thickness. Haemodynamic testing of the MB was performed using an intracoronary pressure/Doppler flow wire at rest and during dobutamine stress. We defined an abnormal diastolic fractional flow reserve (dFFR) as ≤0.76 during stress. The median MB length was 22.9 mm, arterial compression 30.9%, and halo thickness 0.5 mm. The median MMI was 12.1. Endothelial and microvascular dysfunction were present in 85.4% and 22.1%, respectively. At peak dobutamine stress, 94.2% of patients had a dFFR ≤0.76 within and/or distal to the MB. MMI was associated with an abnormal dFFR. CONCLUSIONS: In select patients with ANOCA who have an MB by IVUS, the majority have evidence of a haemodynamically significant dFFR during dobutamine stress, suggesting the MB as being a cause of their angina. A comprehensive invasive assessment of such patients during coronary angiography provides important diagnostic information that can guide management.

Fifty Men, 3510 Marathons, Cardiac Risk Factors, and Coronary Artery Calcium Scores.

INTRODUCTION/PURPOSE: Many male marathon runners have elevated coronary artery calcium (CAC) scores despite high physical activity. We examined the association between CAC scores, cardiovascular risk factors, and lifestyle habits in long-term marathoners. METHODS: We recruited men who had run one or more marathons annually for 25 consecutive years. CAC was assessed using coronary computed tomography angiography. Atherosclerotic cardiovascular disease risk factors were measured with a 12-lead ECG, serum lipid panel, height, weight, resting blood pressure and heart rate, and a risk factor questionnaire. RESULTS: Fifty males, mean age 59 ± 0.9 yr with a combined total of 3510 marathons (median = 58.5, range = 27-171), had a mean BMI of 22.44 ± 0.4 kg·m, HDL and LDL cholesterols of 58 ± 1.6 and 112 ± 3.7 mg·dL, and CAC scores from 0 to 3153. CAC scores varied from 0 in 16 runners to 1-100 in 12, 101-400 in 12, and >400 in 10. There was no statistical difference in the number of marathons run between the four groups. Compared with marathoners with no CAC, marathoners with moderate and extensive CAC were older (P = 0.002), started running at an older age (P = 0.003), were older when they ran their first marathon (P = 0.006), and had more CAD risk factors (P = 0.005), and marathoners with more CAC had higher rates of previous tobacco use (P = 0.002) and prevalence of hyperlipidemia (P = 0.01). CONCLUSION: Among experienced males who have run marathons for 26-34 yr and completed between 27 and 171 marathons, CAC score is related to CAD risk factors and not the number of marathons run or years of running. This suggests that among long-term marathoners, more endurance exercise is not associated with an increased risk of CAC.

The right atrium and tricuspid annulus are cardinal structures in tricuspid regurgitation with or without pulmonary hypertension.

BACKGROUND: Right heart structural abnormalities occur in both tricuspid regurgitation (TR) and pulmonary hypertension (PH). They may occur independently or together, but their joint effects on cardiac structure are incompletely described. This study examined the interactions of TR severity and PH on right heart structural changes. METHODS: The study evaluated 455 patients undergoing both echocardiography and CT angiography (CTA). Cases were divided into 3 groups by TR severity: trace (n=217), mild (n=174), and significant (moderate or severe, n=64). Each TR level was subdivided into two groups by PH absent or present. Cardiac structural measurements included tricuspid annulus area (TAA), right atrial (RA) and right ventricular volume (RV) indexed to body surface area. RESULTS: Analysis by TR and PH showed that indexed RA Volume and TAA were very sensitive to TR severity. RA volume was most affected by pulmonary hypertension when TR was trace or mild, while PH had less effect on TAA. In significant TR, neither RA volume nor TAA were changed by PH. Indexed RV volume was insensitive to trace and mild TR, and PH similarly had little effect. CONCLUSIONS: RA volume and tricuspid annulus area enlarge in proportion to TR severity, trace through significant. PH impacts RA volume but only in trace and mild TR. RA volume best reflects TR impact on right heart structure, both with and without PH. Right atrial volume and tricuspid annulus area are the cardinal indices of TR-induced right heart structural disease et al.l severities. ULTRAMINI ABSTRACT: Right heart structural effects of TR and PH were examined in this study. Patients were evaluated by echo and CTA, and grouped by TR severity as trace, mild, and significant, and were subdivided by PH absence/presence. Analysis by TR severity and PH showed that Indexed RA volume is the parameter most sensitive to TR severity, and PH causes incremental RA volume increases in trace/mild TR. Indexed tricuspid annulus area (TAA) similarly increases with TR severity, but was unaffected by PH at any TR severity. RV volume is insensitive to TR severity and PH. Indexed right atrial volume and tricuspid annulus area are cardinal indices for TR-induced right heart structural disease and increase proportionally to TR severity. RA volume is more sensitive to PH than is tricuspid annular area. TR severity may be more accurately assessed by increased RA volume and annulus area. PERSPECTIVE STATEMENT: The right atrium (RA) and tricuspid annulus (TA) are the cardinal cardiac structures affected by tricuspid regurgitation (TR). They each enlarge with TR severity. The right ventricle exhibits minimal change across TR severity. Pulmonary hypertension (PH) enhances TR-mediated RA and TA dilation, but only in trace and mild TR. PH has no effect on RA, TA, or RV size in significant TR. CENTRAL MESSAGE: Right atrial volume and tricuspid annulus area are the most sensitive to TR severity, and are also sensitive to pulmonary hypertension.

Long-Term Marathon Running Is Associated with Low Coronary Plaque Formation in Women.

INTRODUCTION: Marathon running is presumed to improve cardiovascular risk, but health benefits of high volume running are unknown. High-resolution coronary computed tomography angiography and cardiac risk factor assessment were completed in women with long-term marathon running histories to compare to sedentary women with similar risk factors. METHODS: Women who had run at least one marathon per year for 10-25 yr underwent coronary computed tomography angiography, 12-lead ECG, blood pressure and heart rate measurement, lipid panel, and a demographic/health risk factor survey. Sedentary matched controls were derived from a contemporaneous clinical study database. CT scans were analyzed for calcified and noncalcified plaque prevalence, volume, stenosis severity, and calcium score. RESULTS: Women marathon runners (n = 26), age 42-82 yr, with combined 1217 marathons (average 47) exhibited significantly lower coronary plaque prevalence and less calcific plaque volume. The marathon runners also had less risk factors (smoking, hypertension, and hyperlipidemia); significantly lower resting heart rate, body weight, body mass index, and triglyceride levels; and higher high-density lipoprotein cholesterol levels compared with controls (n = 28). The five women runners with coronary plaque had run marathons for more years and were on average 12 yr older (65 vs 53) than the runners without plaque. CONCLUSION: Women marathon runners had minimal coronary artery calcium counts, lower coronary artery plaque prevalence, and less calcified plaque volume compared with sedentary women. Developing coronary artery plaque in long-term women marathon runners appears related to older age and more cardiac risk factors, although the runners with coronary artery plaque had accumulated significantly more years running marathons.

Needs-Based Innovation in Cardiovascular Medicine: The Stanford Biodesign Process.

More than a decade ago, a formalized fellowship training program in medical device innovation, the first of its kind, was created at Stanford University. Now in its 15th year, the Stanford Biodesign Fellowship Program is a 10-month program whereby postgraduate students with a prior background in medicine, engineering, and/or business form interdisciplinary teams for an experiential process of identifying unmet clinical needs, inventing new solutions, and implementing these ideas (the 3 "I's"). A key component of this structured process is focused attention on needs finding and characterization, which differs from the traditional "tech-push" model (i.e., technologies looking for problems to solve). Although the Stanford Biodesign process can be applied to a wide variety of clinical areas, cardiovascular medicine is particularly well suited, given the breadth of clinical presentations it touches and its history of innovation to solve important clinical problems. Physicians play a vital role in the process, especially for needs identification and characterization. This paper outlines the Stanford Biodesign process and presents an argument for its repeat applicability, discusses its relevance to physicians and to cardiologists in particular, and provides a case study of the process that resulted in a currently available cardiovascular medical technology that came directly from the Fellowship Program.

Functional assessment of multivessel coronary artery disease: ischemia-guided percutaneous coronary intervention.

Invasive evaluation and treatment of coronary artery disease (CAD) has traditionally been based upon coronary angiography to determine the need for and the success of revascularization. However, coronary angiography augmented with fractional flow reserve (FFR) creates a paradigm shift, providing a more complete functional assessment of coronary lesions. Measuring FFR to identify ischemic lesions and guide revascularization results in fewer adverse outcomes, including persistent angina, myocardial infarction, and mortality. An ischemic lesion identified by FFR is more likely to lead to adverse events when compared with an angiographically similar lesion with nonischemic FFR when both are treated medically. Although the mechanism explaining this is unclear, it is likely multifactorial, including the impact of mechanical forces, upregulation of inflammatory mediators, and the amount of distal myocardial tissue at risk. Using both anatomic and ischemia-guided assessments (such as the Functional SYNTAX Score) aids in the therapeutic decision-making process in patients with multivessel CAD. This review focuses on the evidence for FFR-guided management of multivessel CAD.

Increased Coronary Artery Plaque Volume Among Male Marathon Runners.

BACKGROUND: Long-term marathon running improves many cardiovascular risk factors, and is presumed to protect against coronary artery plaque formation. This hypothesis, that long-term marathon running is protective against coronary atherosclerosis, was tested by quantitatively assessing coronary artery plaque using high resolution coronary computed tomographic angiography (CCTA) in veteran marathon runners compared to sedentary control subjects. METHODS: Men in the study completed at least one marathon yearly for 25 consecutive years. All study subjects underwent CCTA, 12-lead electrocardiogram, measurement of blood pressure, heart rate, and lipid panel. A sedentary matched group was derived from a contemporaneous CCTA database of asymptomatic healthy individuals. CCTAs were analyzed using validated plaque characterization software. RESULTS: Male marathon runners (n = 50) as compared with sedentary male controls (n = 23) had increased total plaque volume (200 vs. 126 mm3, p < 0.01), calcified plaque volume (84 vs. 44 mm3, p < 0.0001), and non-calcified plaque volume (116 vs. 82 mm3, p = 0.04). Lesion area and length, number of lesions per subject, and diameter stenosis did not reach statistical significance. CONCLUSION: Long-term male marathon runners may have paradoxically increased coronary artery plaque volume.

Balloon aortic valvuloplasty in high risk aortic stenosis patients with left ventricular ejection fractions <20%.

OBJECTIVES: To determine outcomes following balloon aortic valvuloplasty (BAV) in aortic stenosis (AS) patients with a left ventricular ejection fraction (LVEF) <20%. BACKGROUND: Severe AS patients with a LVEF <20% are excluded from United States (U.S.) transcatheter aortic valve replacement (TAVR) trials and often surgical aortic valve replacement (AVR). The role for BAV to enhance LVEF is unclear. METHODS: Our BAV database of 270 consecutive patients extending from 2005 through 2010 was queried for a preoperative LVEF <20%. Demographics, echocardiograms, procedural technique, and outcomes were analyzed. Pre- and postoperative echocardiograms were used to determine improvement in aortic valve area (AVA) and LVEF. RESULTS: Sixteen patients were identified with a median age of 82 years. The composite Society of Thoracic Surgeons' (STS) mortality risk was 16.4%. The median preoperative AVA and LVEF were 0.60 cm(2) and 16%, respectively, and postoperative AVA and LVEF were 0.77 cm(2) and LVEF 19%, respectively. About 15 of the 16 patients had postoperative echocardiograms available for comparison. And 7 of these 15 (47%) demonstrated improvement in LVEF to ≥20% (median LVEF 25%). The absence of coronary disease and improvement in AVA of ≥0.2 cm(2) was associated with postoperative LVEF of ≥20%. Procedural mortality was 0%. The 30-day, 6-month, and 1-year survival was 69%, 56%, and 29%. STS's mortality risk score ≥15% was associated with short-term mortality. CONCLUSION: With appropriate technique, BAV can be reasonably safe in patients with LVEF <20%. Roughly half of these patients demonstrated improvement in LVEF to ≥20%.

Potential role of three-dimensional rotational angiography and C-arm CT for valvular repair and implantation.

Imaging modalities utilized in the interventional cardiology suite have seen an impressive evolution and expansion recently, particularly with regard to the recent interest in three-dimensional (3D) imaging. Despite this, the backbone of visualization in the catheterization laboratory remains two-dimensional (2D) X-ray fluoroscopy and cine-angiography. New imaging techniques under development, referred to as three-dimensional rotational angiography (RA) and C-arm CT, hold great promise for improving current device implantation and understanding of cardiovascular anatomy. This paper reviews the evolution of rotational angiography and advanced 3D X-ray imaging applications to interventional cardiology.