Khandheria, Bijoy K.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Abstract While atherosclerosis has been suggested as a risk factor for VTE, previously identified mechanisms for atherosclerosis and VTE differ dramatically. Objectives: To compare (a) VTE-free survival and (b) observed vs. expected number of VTE events, among adult patients with and without aortic atherosclerosis. Design/Setting: Population-based prospective cohort study in Olmsted County, MN. Patients: Age- and sex-stratified random sample of the adult (≥45 years old) Olmsted County population identified over the three-year period, 1993–1995 (n=573), performed as part of the Stroke Prevention: Assessment of Risk in the Community (SPARC) study. Measurements: The SPARC study included a baseline clinical evaluation (interviews, review of medical records), blood pressure measurements, blood sampling, and transesophageal echocardiography (TEE). The Risk Factors for VTE in the Community study identified all incident VTE among Olmsted County residents over the 32-year period, 1966–1997, from which expected VTE events by age and sex were calculated. Results: Over 2830 person-years of follow-up, 12 SPARC patients developed VTE (7 idiopathic). The 4-year VTE-free survival was 99% and 98% for those with and those without any TEE-detected aortic atherosclerosis. Adjusting for age in a Cox proportional hazards model, lack of aortic atherosclerosis was significantly associated with subsequent VTE (p=0.01). Among the 276 patients without atherosclerosis observed for 1423 person-years, 7 VTE were observed compared to 2.6 expected (RR=2.7, 95%CI: 1.1, 5.6). Among the 291 patients with atherosclerosis (plaque ≥2mm), 4 VTE were observed compared to 5.8 expected (RR=0.7, 95%CI: 0.2, 1.8). Conclusions: Atherosclerosis is not a risk factor for incident VTE.

Activation Sequence During Atrial PacingIntroductionIn patients with intraatrial conduction delay and sinus node (SN) dysfunction, pacing Bachmann's bundle (BBR) and coronary sinus ostium (CSO) has been suggested to achieve atrial resynchronization with potential beneficial impact on atrial fibrillation and diastolic heart failure. Clinical studies have not shown superiority of one approach.Methods and ResultsWe studied electrical activation sequence in an open‐chest acute canine model of normal atrial function in 8 mongrel dogs under general anesthesia. Bipolar plunge electrodes were distributed over the surface of the atria during unifocal pacing, and intracardiac activation sequence was observed. SN pacing resulted in near‐simultaneous activation at midline sites (BBR and CSO); the left atrium (LA) was activated by anterior and posterior wavefronts simultaneously propagating septally to laterally and meeting at the low‐lateral perimitral LA. Right atrial appendage (RAA) pacing created intra‐RA conduction delay and delayed onset of LA activation. Pacing from RAA, CSO, and BBR resulted in nonsimultaneous activation at midline sites and produced an anteroposterior gradient of LA activation. This phenomenon was seen to the greatest degree with midline pacing and shifted the site of latest activation away from the low‐lateral perimitral LA in all pacing configurations except SN pacing.ConclusionPacing‐induced intra‐LA activation dispersion is enhanced with midline atrial pacing, and secondarily shifts the site of latest activation away from the lateral mitral annulus. Measuring atrial activation times to the low‐lateral perimitral LA can underestimate the degree of atrial dyssynchrony and be misinterpreted as atrial synchrony. Establishing clinical impact requires evaluation of human data.

Background —Atrial septal aneurysm (ASA) is a putative risk factor for cardioembolism. However, the frequency of ASA in the general population has not been adequately determined. Therefore, the frequency in patients with cerebral ischemic events, compared with the frequency in the general population, is poorly defined. We sought to determine the frequency of ASA in the general population and to compare the frequency of ASA in patients with cerebral ischemic events with the frequency in the general population. Methods and Results —The frequency of ASA in the population was determined in 363 subjects, a sample of the participants in the Stroke Prevention: Assessment of Risk in a Community study (control subjects), and was compared with the frequency in 355 age- and sex-matched patients undergoing transesophageal echocardiography in search of a cardiac source of embolism after a focal cerebral ischemic event. The proportion with ASA was 7.9% in patients versus 2.2% in control subjects ( P =0.002; odds ratio of ASA, 3.65; 95% CI, 1.64 to 8.13, in patients versus control subjects). Patent foramen ovale (PFO) was detected with contrast injections in 56% of subjects with ASA. The presence of ASA predicted the presence of PFO (odds ratio of PFO, 4.57; 95% CI, 2.18 to 9.57, in subjects with versus those without ASA). In 86% of subjects with ASA and cerebral ischemia, transesophageal echocardiography did not detect an alternative source of cardioembolism other than an associated PFO. Conclusions —The prevalence of ASA based on this population-based study is 2.2%. The frequency of ASA is relatively higher in patients evaluated with transesophageal echocardiography after a cerebral ischemic event. ASA is frequently associated with PFO, suggesting paradoxical embolism as a mechanism of cardioembolism. In patients with cerebral ischemia and ASA, ASA (with or without PFO) commonly is the only potential cardioembolic source detected with transesophageal echocardiography.

Background—Sildenafil citrate (Viagra) is indicated for the treatment of erectile dysfunction. Large and sudden decreases in systemic blood pressure were reported in a substantial number of patients taking sildenafil citrate combined with nitroglycerin. We studied the effect of sildenafil citrate on the relationship between changes in systemic blood pressure and coronary blood flow.Methods and Results—Healthy male beagles were used to assess systemic blood pressure, pulmonary arterial pressure, and flow in the left circumflex artery (in which a critical stenosis was established) and left anterior descending coronary artery. After measurement of the hemodynamic variables, 2 mg/kg sildenafil citrate was administered via a nasogastric tube. Hemodynamic changes were monitored for 1 hour. Subsequently, the acute effect of nitrate combined with sildenafil citrate was studied by the bolus injection of 0.2 mg isosorbide dinitrate before and after sildenafil citrate. Systemic blood and pulmonary arterial pressures and circumflex flow did not change during this study; however, left anterior descending coronary arterial flow increased from 16.0±5.8 to 24.6±8.7 mL/min 1 hour after administration of sildenafil citrate. The prolongation of systemic blood pressure decrease and the circumflex flow decrement induced by isosorbide dinitrate after sildenafil citrate were significantly larger and longer than those before sildenafil citrate.Conclusions—Sildenafil citrate had the effect of vasodilation in a normal coronary artery; however, a combined effect with nitrate resulted in large and protracted decreases in systemic blood pressure and coronary blood flow in vessels with critical stenosis.

Background —Atherosclerosis of the thoracic aorta is associated with stroke. The association between hypertension, a major risk factor for stroke, and aortic atherosclerosis has not been determined in the general population. Methods and Results —Transesophageal echocardiography was performed in 581 subjects, a random sample of the Olmsted County (Minnesota) population aged ≥45 years participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. Blood pressure was assessed by multiple office measurements and 24-hour ambulatory blood pressure monitoring. The association between blood pressure variables and aortic atherosclerosis was evaluated by multiple logistic regression, adjusting for other associated variables. Among subjects with atherosclerosis, blood pressure variables associated with complex aortic atherosclerosis (protruding plaques ≥4 mm thick, mobile debris, or ulceration) were determined. Age and smoking history were independently associated with aortic atherosclerosis of any degree ( P ≤0.001) and with complex atherosclerosis ( P =0.002), whereas sex, diabetes mellitus, and body mass index were not. Multiple systolic and pulse pressure variables (office and ambulatory), but none of the diastolic blood pressure variables, were associated with atherosclerosis and complex atherosclerosis, adjusting for age and smoking. Among subjects with atherosclerosis, the odds of complex atherosclerosis increased as ambulatory out-of-bed systolic blood pressure increased (odds ratio 1.43 per 10 mm Hg increase, 95% CI 1.10 to 1.87) and with hypertension treatment, adjusting for age and smoking history. Conclusions —High blood pressure is independently associated with aortic atherosclerosis. Among subjects with atherosclerosis, high blood pressure is associated with complex atherosclerosis.

Background Transesophageal echocardiography (TEE) is the diagnostic modality of choice for visualizing the left atrial appendage (LAA). This study defined the morphology of the LAA in normal autopsy specimen hearts and considered the implications of these findings for TEE studies. Methods and Results Five hundred normal autopsy hearts were reviewed (25 male and 25 female subjects from each decade for 10 decades). LAA length, width, orifice size, and number of lobes were recorded. Number of lobes was compared between sexes with the rank sum test and regressed against age. Mean length, width, and orifice size increased with age, up to age 20 years, in both sexes. Rates were significantly different between sexes for LAA size ( P =.011) and width ( P =.006). After age 20, statistically significant but clinically insignificant age-related changes were observed. Fifty-four percent of LAAs had two lobes (range, 1 to 4), with no age or sex differences. Lobes exist in different planes of the heart. Most pectinate muscles were ≥1 mm in width. Pectinate muscles <1 mm (2.6% of cases) were seen in only the first and last decades. Conclusions Age- and sex-related differences in LAA dimensions exist. These differences and the existence of multilobed appendages are important in the accurate TEE evaluation of LAA. Because lobes exist in different planes, imaging must be done in multiple planes to visualize the entire LAA.

Background An atrial septal aneurysm (ASA) is a well-recognized abnormality of uncertain clinical relevance. We reevaluated the clinical significance of ASA in a large series of patients. The aims of the study were to define morphological characteristics of ASA by transesophageal echocardiography (TEE), to define the incidence of ASA-associated abnormalities, and to investigate whether certain morphological characteristics of ASA are different in patients with and without previous events compatible with cardiogenic embolism. Methods and Results Patients with ASA were enrolled from 11 centers between May 1989 and October 1993. All patients had to undergo transthoracic and transesophageal echocardiography within 24 hours of each other; ASA was defined as a protrusion of the aneurysm >10 mm beyond the plane of the atrial septum as measured by TEE. Patients with mitral stenosis or prosthesis or after cardiothoracic surgery involving the atrial septum were excluded. Based on these criteria, 195 patients 54.6±16.0 years old (mean±SD) were included in this study. Whereas TEE could visualize the region of the atrial septum and therefore diagnose ASA in all patients, ASA defined by TEE was missed by transthoracic echocardiography in 92 patients (47%). As judged from TEE, ASA involved the entire septum in 100 patients (51%) and was limited to the fossa ovalis in 95 (49%). ASA was an isolated structural defect in 62 patients (32%). In 106 patients (54%), ASA was associated with interatrial shunting (atrial septal defect, n=38; patent foramen ovale, n=65; sinus venosus defect, n=3). In only 2 patients (1%), thrombi attached to the region of the ASA were noted. Prior clinical events compatible with cardiogenic embolism were associated with 87 patients (44%) with ASA; in 21 patients (24%) with prior presumed cardiogenic embolism, no other potential cardiac sources of embolism were present. Length of ASA, extent of bulging, and incidence of spontaneous oscillations were similar in patients with and without previous cardiogenic embolism; however, associated abnormalities such as atrial shunts were significantly more frequent in patients with possible embolism. Conclusions As shown previously, TEE is superior to the transthoracic approach in the diagnosis of ASA. The most common abnormalities associated with ASA are interatrial shunts, in particular patent foramen ovale. In this retrospective study, patients with ASA (especially with shunts) showed a high frequency of previous clinical events compatible with cardiogenic embolism; in a significant subgroup of patients, ASA appears to be the only source of embolism, as judged by TEE. Our data are consistent with the view that ASA is a risk factor for cardiogenic embolism, but thrombi attached to ASA as detected by TEE are apparently rare.