Klarich, Kyle W.

Background. Apical hypertrophic cardiomyopathy (AHCM) has been considered a ``benign” form of HCM in Asian and non-Asian patients (pt). However, data on long-term outcome of pt with AHCM are limited. The purpose of this study was to determine the natural history of pt with AHCM followed at a tertiary referral center in North America. Methods. Between July 1976 and September 2006, 193 pt with the diagnosis of AHCM were seen at the Hypertrophic Cardiomyopathy Clinic. The last echocardiographic exam was reviewed in all pt. Follow-up data were obtained where possible (clinic visit). Results. Mean age at diagnosis 56±17 years, mean age at first presentation at our center was 58±17 years. Symptoms included chest pain in 69 pt (36 %), and exertional dyspnea ≥NYHA II in 97 pt (50 %). A family history of either HCM and/or sudden cardiac death was reported by 36 pt (19 %). Coronary artery disease was proven in 40 pt (21 %). Median follow up was 50 months (1–318) and obtained in 124 pt (64 %). The following events were reported at the last clinic visit: heart failure in =5 pt, syncope in =0 pt, ventricular tachycardia in =7 pt, ICD implantation in 22 pt, and stroke in 22 pt. Death from all causes occurred in 51 of 193 pt (26 %) at a mean age of 72 years (14–78). Kaplan-Meier survival analysis was used to examine survival from all causes of death since first presentation. Observed survival in patients with AHCM was significantly less than expected in an age- and gender matched Minnesota white population (p=0.009). The observed survival at 5, 10 and 15 years was 87 %, 82 %, and 57 % respectively, while the expected survival for these time points was 91 %, 81 %, and 72 %. Conclusions. AHCM in this predominantly North American patient population is associated with an increased mortality. Patients with AHCM have a high incidence of significant cardiovascular symptoms and ventricular arrhythmias. As the disease is less benign than previously suspected, careful longitudinal care by a cardiologist is warranted.

Objective To compare the prevalence and patterns of anomalous coronary artery origin from the opposite sinus (ACAOS) in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). Methods Retrospective review of consecutive patients with surgically excised BAV and TAV was performed from 1994 to 2015. Clinical notes, echocardiograms, coronary angiograms, CT angiographies, and pathology reports were reviewed. ACAOS included right coronary artery from the left cusp, left circumflex artery from the right cusp and left main or left anterior descending artery from the right cusp. Results 2371 (years 1994–2015) and 1679 (years 2009–2015) consecutive patients with pathology-confirmed BAV and TAV, respectively, and defined preoperative coronary anatomy were identified. A left dominant coronary circulation was present in 386 (18%) patients with BAV and 179 (11%) patients with TAV (p<0.001). ACAOS was identified in 43 (1.8%) patients with BAV and 15 (0.9%) patients with TAV, p=0.02. Among patients with BAV and ACAOS, the most common phenotype was right-left fusion (n=34, 79%) with present raphe (n=36, 84%), with no association between BAV phenotype and ACAOS type. On multivariate analysis, BAV status and size of the mid-ascending aorta were independently associated with ACAOS (OR 3.29; CI 1.26 to 8.6; p=0.02; OR 0.93; CI 0.87 to 0.98; p=0.01; respectively). Only two patients with ACAOS, one with BAV and one with TAV, had a perioperative coronary ischaemic event. Conclusions The prevalence of the potentially malignant ACAOS is significantly higher (threefold higher odds) in patients with BAV as compared with TAV, yet remains uncommon in absolute terms. Most patients with BAV and ACAOS had right-left cusp fusion and present raphe. Perioperative coronary events are rare in patients with ACAOS.

Background: Papillary fibroelastoma (PFE) is the most common benign cardiac tumor. Because PFEs have the potential to embolize, they typically are surgically excised. Prior studies have suggested that postoperative recurrence of PFE is rare or does not occur. Objectives: To determine the rate at which PFEs recurred after surgical removal and to identify any risk factors associated with recurrence. Methods: Patients with pathologically proven PFE were retrospectively identified from a single center. Patients were included in the study if they had an echocardiographic examination at least 1 year after surgery. Echocardiographic images obtained intraoperatively (after excision) and at dismissal were compared with those of the most recent examination to assess the possibility of PFE recurrence. Results: Ninety eight patients were identified. The mean (SD) duration of follow-up was 5.4 (3.7) years (range, 1-17 years). Twelve patients (12.2%) had echocardiographically proven PFE recurrence. Three patients had the recurrent lesion surgically re-excised, and pathologic analysis showed that 2 were recurrent PFEs and 1 was a Lambl excrescence. Clinical presentation of stroke or TIA was more common for the recurrence patients (for the first PFE) than for the nonrecurrence patients (83% vs 26%; P <.001). Conclusions: Contrary to published data, PFEs do recur after surgical excision. This emphasizes the importance of postoperative follow-up with transesophageal echocardiography for identifying recurrent masses. Table. Characteristics of Patients With Recurrent PFE Abbreviations: AV, aortic valve; LA, left atrium; LE, Lambl excrescence; LVOT, left ventricular outflow tract; MV, mitral valve; PV, pulmonary valve; RA, right atrium; RC, right cusp; TV, tricuspid valve. a Corresponds to the same location. b Corresponds to a different location .

Abstract Funding Acknowledgements Type of funding sources: None. Background Papillary fibroelastoma (PFE) is now regarded as the most common primary tumor of the heart. Although benign, they are clinically significant for their high risk of embolization. They are most commonly found on cardiac valves but can also be present on non-valvular endocardial surfaces. The aim of this study was to better characterize patients with left-sided non-valvular PFE and its clinical sequelae. Methods We retrospectively identified patients with pathology-proven PFEs at a single center between January 1995 and December 2018 (n = 279). Patients with left-sided non-valvular PFE were analyzed. Medical records were retrospectively reviewed for clinical characteristics and outcomes. In addition, intra-operative transesophageal echocardiograms were manually reviewed to estimate overall size and location. Results During the study period, we identified 37 patients with left-sided non-valvular PFE (mean age 61 ± 14 years; 62% females) (Table). PFEs were located on the left ventricle in 41%, left atrium in 35%, and left ventricular outflow tract in 24% of patients. Around a quarter of patients (27%) had a diagnosis of hypertrophic cardiomyopathy, 19% had prior cardiac surgery, and 27% had cancer diagnosed prior to PFE diagnosis. Transient ischemic attack or stroke was the presenting symptom in 22% of patients, myocardial infarction in 6% and peripheral embolization in 6%. Median maximal length for PFE on the left ventricle was 11.1 mm [3;18], on the left atrium 9 mm [2;25], and left ventricular outflow tract 8 mm [6;13]. A minority of patients (9/37 [24%]) had associated valvular PFE on the mitral valve and/or aortic valve (1 patient had both mitral valve and aortic valve PFE, 7 had aortic valve PFE and 1 had Mitral valve PFE). Only 13 patients had follow up transthoracic/transesophageal echocardiogram 1 year after PFE removal; 4/13 (31%) had documented PFE recurrence (3 PFE recurred in the same location as the original; 1 in a different location). Conclusion Left-sided non-valvular PFE is associated with thromboembolic events and at least in those that had follow-up echocardiograms, had a high recurrence rate. More studies are needed to evaluate the management of patients with asymptomatic PFE. Abstract Figure. Baseline Characteristics

Variables in cardiology fellowship applications have not been objectively analyzed against applicants' subsequent clinical performance. We investigated possible correlations in a retrospective cohort study of 65 cardiology fellows at the Mayo Clinic (Rochester, Minn) who began 2 years of clinical training from July 2007 through July 2013. Application variables included the strength of comparative statements in recommendation letters and the authors' academic ranks, membership status in the Alpha Omega Alpha Honor Medical Society, awards earned, volunteer activities, United States Medical Licensing Examination (USMLE) scores, advanced degrees, publications, and completion of a residency program ranked in the top 6 in the United States. The outcome was clinical performance as measured by a mean of faculty evaluation scores during clinical training. The overall mean evaluation score was 4.07 ± 0.18 (scale, 1–5). After multivariable analysis, evaluation scores were associated with Alpha Omega Alpha designation (β=0.13; 95% CI, 0.01–0.25; P=0.03), residency program reputation (β=0.13; 95% CI, 0.05–0.21; P=0.004), and strength of comparative statements in recommendation letters (β=0.08; 95% CI, 0.01–0.15; P=0.02), particularly in letters from residency program directors (β=0.05; 95% CI, 0.01–0.08; P=0.009). Objective factors to consider in the cardiology fellowship application include Alpha Omega Alpha membership, residency program reputation, and comparative statements from residency program directors.

AbstractObjectivesThe aim of this study was to assess the 30 day incidence of paravalvular leak (PVL) and need for aortic valve reintervention of a fourth generation balloon expandable transcatheter valve with enhanced skirt (4G‐BEV) (SAPIEN 3 Ultra) compared with a third generation balloon expandable transcatheter valve (3G‐BEV) (SAPIEN 3).BackgroundThe incidence of PVL has steadily declined with iterative improvements in transcatheter aortic valve replacement (TAVR) technology and implantation strategies.MethodsPatients who underwent TAVR at Mayo Clinic from 7/2018 to 7/2019 were included in a prospective institutional registry. 4G‐BEV has been utilized since 2/2019, and, after this date, 3G‐BEV and 4G‐BEV were simultaneously used. 4G‐BEV had three sizes (20, 23, and 26 mm) while 3G‐BEV included four sizes (20, 23, 26, and 29 mm). Both cohorts were evaluated at 30 days post‐TAVR with a transthoracic echocardiogram to assess for PVL.ResultsA total of 260 consecutive patients were included. Of these, 101 patients received a 4G‐BEV and 159 patients received a 3G‐BEV. There were more females (p = .0005) and a lower aortic valve calcium score (p = .02) in the 4G‐BEV cohort at baseline. Age, STS risk score, NYHA Class, and aortic valve mean gradient did not differ between groups. 4G‐BEV was associated with a lower incidence of mild PVL (10.8 vs. 36.5%; p < .0001) and moderate PVL (0 vs. 5.8%) compared to the 3G‐BEV at 30 days. There was no association between PVL and valve size in either cohort.ConclusionsUtilization of 4G‐BEV is associated with reduced PVL at 30 days post‐TAVR compared with 3G‐BEV.

Abstract Background Papillary fibroelastoma (PFE) is a rare benign cardiac tumor with embolic potential. It is most commonly found on cardiac valves but can also be present on non-valvular endocardial surfaces. We sought to better understand the average PFE growth and recurrence rates, and characteristics that might be associated with embolization. Purpose To examine growth and recurrence rates and factors associated with embolization in patients with pathology-proven PFE. Methods Pathology-proven PFEs from 279 patients were identified at a single center between January 1995 and December 2018,and those with at least two transesophageal echocardiograms (TEE) more than 30 days apart were analyzed (n=62). Medical records were retrospectively reviewed for clinical characteristics and outcomes. In addition, intra-operative TEEs were manually reviewed and compared to previous TEEs at our institution to estimate overall size, location, and average PFE growth rates. Results The TEEs from 62 patients with pathology-proven PFE (mean age 65±12 years, female 63%) were reviewed. PFE was discovered incidentally during cardiac surgery in 18% of patients. Most PFEs were located on the aortic valve (AV) (73%) followed by the mitral valve (MV) (16%). The majority of PFEs (71%) presented with a stalk versus a sessile configuration. Average maximal length for PFE (including stalk if present) on the AV was 8.5±3.3 mm, and on the MV 6.8±2.0 mm. The number of PFEs located in other locations was too small to be analyzed for growth. PFE growth varied depending on location and configuration. The PFE growth on the AV was an average increase of 0.47 mm/year, those on the MV was 0.115 mm/year. Valvular PFE was associated with significant functional valve abnormality in 15% of patients, and the abnormality was attributed to the PFE in 9% of patients. There were 25 patients (40%) who had a documented stroke/transient ischemic attack prior to PFE removal (46% located on AV, 44% on MV, 10% other locations). In addition, some patients had other documented embolic complications, such as myocardial infarction, amaurosis fugax, and peripheral embolization to the spleen and kidney. PFE size and location (up-/ downstream of the valve) were not predictive of cardiovascular thromboembolic events. At a median follow up of 2 years, PFEs recurred in the same location in 7.5% of the patients. Conclusion PFE is highly associated with thromboembolic events and seem to grow slowly, with an average growth rate of 0.47mm/year on AV and 0.115mm/year on MV. Growth rates for PFE have not been previously described. PFE can be safely excised with preservation of the native valve and recurs in 7.5% of patients, suggesting that close follow-up maybe warranted.

Abstract Background: Amyloidosis is a multisystem disease with extracellular deposition of pathological insoluble beta-fibrillar proteins. Involvement of the heart is seen in more than one-half of the patients with systemic AL amyloidosis and it is the most important determinant of clinical outcome. Cardiac amyloidosis is a restrictive infiltrative cardiomyopathy in which, despite declines in stroke volume that accompany disease progression, the ejection fraction (EF) often remains preserved even in advanced stages of the disease. King et al. proposed a novel index of myocardial function, the myocardial contraction fraction (MCF), defined as the ratio of stroke volume (SV) to myocardial volume (MV). MCF is a measure of myocardial shortening, which differentiated myocardial performance in patients with similar degrees of hypertrophy and in a recent small cohort of AL amyloidosis patients appeared superior to left ventricular ejection fraction (EF) in predicting overall survival (OS). It was our goal to assess the prognostic role of MCF in a large cohort of patients with AL amyloidosis in the context of other prognostic variables. Methods: Patients seen between 4/1/1999 and 2/1/2015 were eligible for this retrospective study if they had an ECHO at the Mayo Clinic, Rochester, MN within 30 days of their AL amyloidosis diagnosis with measurements of left ventricular chamber size and wall thickness needed to calculate MCF, EF, and the presence or absence of pericardial effusion. To capture the full cohort, modeling was done first excluding Mayo (2012) staging and global averaged left ventricular longitudinal peak systolic strain (LV strain) since limited numbers of patients had these studies, 342 and 294, respectively. Thresholds of continuous variables were chosen based on receiver operator curves targeting death at 1-year. Cox proportional hazards analysis was used to identify factors that were prognostic for OS. Statistical analyses were done using JMP 9.0 (SAS, Cary, NC). Results: Among the 722 patients satisfying entry criteria,median age was 64 years (range 32-94) and 66% were male. The best cutoff for MCF was 21% (sensitivity: 74%, specificity: 60%; AUC=0.699) and distinguished two groups with different OS (median 53 vs. 9 months, P<0.0001; Figure). On univariate analysis the baseline ECHO variables predicting OS were interventricular septum thickness (IVS) >12 mm (RR 1.8, P=0.0002), EF <60% (RR 1.7), MCF ≤21% (RR 2.1), and presence of pericardial effusion (RR 2.0), all with P<0.0001. On multivariate MCF ≤21% (RR 1.6, P <0.0001), EF <60% (RR 1.4, P=0.0007) and the presence of pericardial effusion (RR 1.3, P=0.002) were independent predictors of OS. Additional modeling was done with the subset of 342 patients who were assessable for Mayo (2012) staging, (i.e. measurements of immunoglobulin free light chain, NT-proBNP, and troponin T). On univariate analysis, patients with a Mayo (2012) stage ≥ 3 had a RR 2.1, p<0.0001. On multivariate, only MCF ≤21% (RR 1.5, P =0.01), Mayo (2012) stage ≥ 3 (RR 1.5, P=0.01) and EF<60% (RR 1.7, P=0.0006) were independent prognostic determinants. Finally, we addressed LV-strain among the 294 patients in whom the study was performed. There was a significant correlation between MCF and LV strain (rho =-0.86, P<0.0001). On univariate, LV-strain less negative than -13 generated a RR of 2.3, p<0.0001. In contrast to the model containing MCF, on LV-strain multivariate, EF was no longer significant, but LV-strain less negative than -13 (RR 2.0, P=0.008) and Mayo (2012) stage ≥ 3 (RR 2.0, P=0.008) predicted independently OS. Conclusions: MCF ≤21% identified a subgroup of patients with a high mortality risk, and it was independent of the Mayo (2012) staging but highly correlated with LV strain. An advantage of MCF, which is a novel volumetric measurement of the left ventricular chamber, is that, unlike LV-strain, MCF is simple to calculate from routine ECHO measures. Figure 1. Overall survival of 722 patients according to MCF<21%. Figure 1. Overall survival of 722 patients according to MCF<21%. Disclosures Kumar: AbbVie: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Skyline, Noxxon: Honoraria; Celgene, Millenium, Sanofi, Skyline, BMS, Onyx, Noxxon,: Other: Consultant, no compensation,; Sanofi: Research Funding; Millenium/Takeda: Research Funding; Onyx: Research Funding.

Background: Heart involvement is the most important prognostic determinant in AL amyloidosis patients. Echocardiography is a cornerstone for the diagnosis and provides important prognostic information. Methods and Results: We studied 754 patients with AL amyloidosis who underwent echocardiographic assessment at the Mayo Clinic, including a Doppler-derived measurement of stroke volume (SV) within 30 days of their diagnosis to explore the prognostic role of echocardiographic variables in the context of a well-established soluble cardiac biomarker staging system. Reproducibility of SV, myocardial contraction fraction, and left ventricular strain was assessed in a separate, yet comparable, study cohort of 150 patients from the Pavia Amyloidosis Center. The echocardiographic measures most predictive for overall survival were SV index <33 mL/min, myocardial contraction fraction <34%, and cardiac index <2.4 L/min/m 2 with respective hazard ratios (95% confidence intervals) of 2.95 (2.37–3.66), 2.36 (1.96–2.85), and 2.32 (1.91–2.80). For the subset that had left ventricular strain performed, the prognostic cut point was −14% (hazard ratios, 2.70; 95% confidence intervals, 1.84–3.96). Each parameter was independent of systolic blood pressure, Mayo staging system (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and troponin), and ejection fraction on multivariable analysis. Simple predictive models for survival, including biomarker staging along with SV index or left ventricular strain, were generated. Conclusions: SV index prognostic performance was similar to left ventricular strain in predicting survival in AL amyloidosis, independently of biomarker staging. Because SV index is routinely calculated and widely available, it could serve as the preferred echocardiographic measure to predict outcomes in AL amyloidosis patients.