Aguilar, Maria I.

Background: Optimum timing of surgery for severe primary mitral regurgitation (MR) particularly in the absence of significant symptoms or echo evidence of LV impairment remains unclear. Other modalities of assessment include cardiopulmonary exercise testing (CPET) and novel echo measurements, such as LV global longitudinal strain (LVGLS). We sought to evaluate whether pre-op CPET or LVGLS are associated with survival after surgery. Methods: We identified consecutive patients who had surgery for severe primary MR between 2007 and 2017 and had pre-op CPET. Clinical and mortality data were collected from chart review and our institutional database. LVGLS was retrospectively collected by a single person blinded to patient outcomes. Primary outcome was post surgery all cause death, and we used univariable analysis to identify variables associated with all cause death. Results: We included 176 patients with median age 63 (IQR 51, 71) years, 63 patients (35.8%) were female and 31 patients (14.8%) had a history of atrial fibrillation. 165 patients (93.8%) had mitral repair, 18 (10.2%) had concomitant CABG, 22 (12.5%) had concomitant ablation procedure and 14 (8.0%) had concomitant tricuspid procedure. 114 patients (64.8%) were in NYHA Class I and 56 (31.8%) were in NYHA Class II. There was no operative mortality. Median % predicted peak VO2 (ppVO2) was 89 (74, 101), median ventilatory equivalent of carbon dioxide (VE/VCO2) was 28.0 (25.7, 31.0) l/min/l/min and median respiratory exchange ratio was 1.2 (1.1, 1.2). 73 patients (41.5%) had abnormal CPET (defined as ppVO2<85%). Median LVEF was 65 (60, 68) %, median LVESD was 35 (32, 38) mm and median LVGLS was 18.5 (16.6, 20.3) %. 45 patients (25.9%) had abnormal LVEF (defined as ≤ 60%), 11 patients (6.7%) had abnormal LVESD (defined as ≥45mm) and 35 patients (20.8%) had abnormal LVGLS (defined as <16%). At a median follow up of 10.2 (6.8, 13.2) years, there were 19 (10.8%) deaths. In the univariate analysis, age at surgery (HR 1.12, p<0.001), LVESD (HR 1.11, p=0.009), LVGLS (HR 1.11, p=0.013) and VE/VCO2 (HR 1.08, p=0.044) were associated with all cause mortality. Conclusion: A significant proportion of patients with no or mild symptoms exhibit echocardiographic evidence of LV impairment when having surgery for severe primary MR. CPET parameters such as VE/VCO2 and novel echocardiographic measurements such as LVGLS may predict risk of long term mortality and potentially inform timing of surgery in these patients.

Abstract Introduction Cardiopulmonary exercise testing (CPET) parameters such as peak VO2 ≤ 14ml/kg/min, percentage predicted peak VO2 (ppVO2) ≤ 50% and ventilation equivalent of carbon dioxide (Ve/VCO2) &gt;35 l/min/l/min are recommended thresholds to list for isolated heart transplant. There is minimal data on clinical events after listing to guide clinical management or priority in organ allocation. Purpose To assess the effect of peak VO2, ppVO2, Ve/VCO2 on clinical events after listing for isolated heart transplant. Methods In a single centre retrospective study, we identified patients who were status 6 or status 2 prior to 2018 at time of listing for isolated heart transplant between 2007 and 2021. Clinical data were collected by chart review. Primary outcome of progressive heart failure was defined as death or upgrade in transplant priority status (new inotropes or mechanical circulatory support). Comparison was made between peak VO2 strata (&gt; 14 vs ≤ 14 ml/kg/min), ppVO2 strata (&gt; 50% vs 40-50% vs &lt;40%) and Ve/VCO2 strata (&lt;35 vs &gt;35 l/min/l/min). Secondary outcome was time dependent survival after listing for heart transplant. Results We identified 141 patients of which 133 underwent CPET and follow up was available for 130 who were included in the analysis. Median age was 53 years (interquartile range 41-59 years), 29.1% of patients were female. Median peak VO2 was 14.0 ml/kg/min (11.2-15.7), ppVO2 was 44% (36-52), Ve/VCO2 slope was 34.0 (31.0-37.0) and RER was 1.1 (1.1-1.2). 87 patients had progressive heart failure consisting of 34 deaths and 83 patients having upgrade in priority status. There was a significant difference in risk of progressive heart failure comparing peak VO2 strata (Figure 1) (freedom from event at one year 71.4% with peak VO2 &gt; 14 vs 46.5% with peak VO2 ≤ 14, p=0.00061) and ppVO2 strata (Figure 2) (freedom from event at one year 75.0% with ppVO2 &gt;50% vs 61.2% with ppVO2 40-50% vs 42.6% with ppVO2 &lt;40%, p=0.0015). There was no significant difference with Ve/VCO2 strata (freedom from event at one year 59.8% with Ve/VCO2 &lt;34 vs 54.9% with Ve/VCO2 &gt;34, p=0.52). There were 34 deaths before transplant and 23 deaths after transplant. 87 patients underwent transplant. In a time dependent survival analysis, age, gender and ppVO2&lt;50% (HR 1.65 (0.87-3.12)) were not significant predictors of mortality. Both early transplant (defined as &lt; 1 year after listing, HR 0.14 (0.06-0.34) and late transplant (defined as &gt; 1 year after listing, HR 0.16 (0.08-0.32)) were significant predictors of lower mortality whilst Ve/VCO2&gt;35 (HR 2.09 (1.19-3.68)) was a significant predictor of higher mortality. Conclusions Peak VO2 and ppVO2 stratify risk of progressive heart failure in ambulatory patients awaiting isolated heart transplant. However, Ve/VCO2 is a predictor of significantly higher mortality. These findings should affect clinical management and transplant priority status; and influence revision of future guidelines.Freedom from event by peak VO2 strataFreedom from event by ppVO2 strata

Background: Each year, nearly 700,000 Americans suffer from strokes, resulting in 150,000 deaths and significant disability among survivors. Despite advances in therapeutic options for acute stroke within a critical time window, patient delay in seeking medical attention remains a significant barrier to improving outcomes. In a recent study of the effect of marital status on the timing of presentation for medical care in patients with chest pain, married men presented earlier than married women. In this study, we hypothesize that marital status is a predictor of earlier health-seeking behavior following the onset of stroke symptoms. Methods: We conducted a retrospective review of 100 patients with acute stroke symptoms in our stroke alert quality initiative database who were brought by Emergency Medical Services (EMS) to the Mayo Clinic Hospital, Arizona between December 1, 2010 and June 30, 2011. Nine patients were excluded due to lack of data. The database contains the following information for each patient: age, gender, marital status, the time of symptom awareness, and the time of EMS dispatch. Using both an independent samples t-Test and ANOVA, we compared the time from symptom awareness to EMS dispatch both between married and single patients, and between men and women, (married and single). Results: The mean age of the 91 patients studied was 76 years (SD = 12.5 years) and 52% were women. Forty-five patients (49.5%) were married, and 46 (50.5%) were single. The mean time from symptom awareness to EMS activation was 52 minutes (median 21.0, SD 87.3, range 2-519 minutes.) Categorized by marital status, married patients activated EMS earlier that single patients, but this difference was not significant (43 versus 60 minutes, p=0.35.). Analyzing the data separately for gender, we found that married men activated EMS significantly earlier than married women (26 versus 72 minutes, p=0.04.). Single men activated EMS earlier than single women, but this difference was not significant (50 versus 66 minutes, p=0.60.) Conclusions: Among persons with acute stroke symptoms, earlier medical-seeking behavior was seen in married compared to single persons, and particularly in married men. We plan to analyze a larger sample of patients, and if these preliminary findings are confirmed, we will conduct a prospective study evaluating reasons why married men with stroke symptoms seek medical attention earlier.

Background: Although not without its limitations, warfarin has provided essential protection against cardioembolic stroke in nonvalvular atrial fibrillation (NVAF) for over 60 years. Dabigatran, the first oral direct thrombin inhibitor to be approved in the United States is reputed to provide the same or better ischemic stroke protection with reduced risk of intracranial hemorrhage. However, it remains to be seen whether its promise will be borne out in everyday practice. Objective: Track initial dabigatran course in patients at Mayo Clinic Arizona and regional stroke centers since its approval in 2010. Methods: Retrospective chart review of all dabigatran patients between October 2010 and September 2011. Regional practices were obtained from a nationwide survey of cardiologists and neurologists. Results: See table Conclusion: During our period of review, dabigatran was well tolerated. A smaller than expected number of patients discontinued the agent or experienced adverse events, as compared to randomized controlled trial predictions. Furthermore, rates of ischemic events (2/159 or 1.26%) were exceedingly low. Our study had several limitations (retrospective review; random bias, sample bias with low numbers and a more elderly population, shorter median follow up). Many of these shortcomings could be addressed with prospective patient tracking. As with any novel therapy, provider surveys afforded an important window into real world practices and perceptions regarding dabigatran. The majority believed it was a reasonable alternative to warfarin, citing fluctuating INR’s as the most persuasive target population followed by patient preference. Cost was an important limiting factor to prescription and considerable uncertainty remains surrounding reversibility and how to approach acute thrombolysis in recurrent ischemic stroke.

Background: Atrial fibrillation (AF) is an important modifiable and independent risk factor for stroke. AF is associated with 2-4% annual risk for first time stroke and about 8% annually for recurrent stroke. Anticoagulant therapy reduces the risk by 60%, while the relative risk reduction (RRR) obtained from antiplatelet therapy is only 20%. The effect is more robust for secondary than for primary prevention. Risk stratification schemes are utilized to assess an individual’s risk of future stroke and to determine the optimal antithrombotic or anticoagulation regimen for stroke prevention. Despite Warfarin’s superiority over antiplatelet therapy to reduce the risk of AF related systemic embolism, Warfarin is largely underutilized. The aim of this study was to determine the frequency and reasons behind withholding anticoagulation in patient with AF related cardioembolic stroke in our institution. Method: We extracted patients from our Get With The Guideline’s (GWTG) database who were admitted to Mayo Clinic AZ between January 2004 and December 2009. Two authors (TK and NL) independently identified all patients with the diagnosis of atrial fibrillation who were not prescribed Warfarin therapy upon discharge, then reviewed to identify the reason(s) why anticoagulation was not initiated. Factors such as discharge disposition (home, acute rehabilitation, long term nursing facility, hospice, other) and functional status (able to ambulate independently, with assistance, unable to ambulate, or not documented) were also assessed to help support the decision process. Results: From a total of 1295 patients, 305 with AF were identified. Patients who expired 48 (3.7%) from un-related causes were excluded. Of the 257 patients, 206 (80.2%) were anticoagulated and 51 (19.8%) were not anticoagulated. We found that in the anticoagulated group, patients discharged home were more likely to receive anticoagulation (89.2%), followed by those discharged to acute rehabilitation and skilled nursing facilities (77%). Those discharged to hospice were the least likely to receive anticoagulation (6.4%). In addition, patients with greater functional ability were also more likely to receive anticoagulation (independent 89.8%, vs. assisted 76.7%, vs. non-ambulatory 33.3%; p<0.0001). Reasons to withhold anticoagulation therapy at discharge included terminal illness/comfort measures only (40.0%); risk/discomfort due to bleeding (24%); risk of falls (13.0%); and patient refusal (9.0%). Discussion: Based on the results, we conclude that functional status and disposition at discharge are significant factors influencing the decision to anticoagulate after cardioembolic stroke attributed to AF.

Introduction: Recent reports have linked visit-to-visit blood pressure (BP) variability to risk of mortality and stroke, independent of the effect of mean BP level. We sought to confirm these findings in the Cardiovascular Health Study (CHS), a cohort study of cardiovascular risk factors. Hypothesis: Variability in visit-to-visit SBP, defined as intraindividual SBP SD, is directly associated with risk of mortality, myocardial infarction (MI), and stroke, independent of intraindividual SBP mean and trend over time. Methods: Participants from CHS were eligible if they attended their first five annual clinic visits and did not have stroke, MI, or death by the 5th visit (N=3513). Follow-up started at the 5th visit and extended through June 2008. Analyses were further restricted to subjects who used no antihypertensive medications during the entire 5-year baseline period (non-users, n=1570) and subjects who used the same antihypertensive regimen during that time (users, n=978). Intraindividual SBP variables were defined using each subject’s 5-visit BPs. Cox proportional hazards models estimated adjusted hazard ratios (HR) per standard deviation (SD) increase in intraindividual SD (iSD) SBP or intraindividual mean (iMean) SBP. Results were stratified on medication use or non-use. Results: Participants’ mean age was 71 years, 42% were men, and 95% were white. Mean(SD) of iSD SBP was 9.8(4.6) mmHg for anti-hypertensive medications non-users and 12.0(6.0) mmHg for users. iMean SBP was significantly associated with all 3 outcomes among non-users and with stroke among users (table). iSD SBP was significantly associated with mortality in all participants and with MI among non-users; associations for stroke were not significant. Conclusion: Long-term visit-to-visit SBP variability may be an important determinant of MI and mortality risk in the elderly. Results for stroke are not consistent with other, previous reports. More research is needed to determine the clinical implications.

Introduction: Despite the recognized linkage between retinal microvascular abnormalities and cerebrovascular ischemic diseases (CVD), the retinal findings’ standardization and the degree of association remain unclear. We aimed to investigate the quantitative association between various retinal microvascular signs and CVD. Hypothesis: retinal microvascular abnormalities best predictive of CVD could be identified by synthesizing estimates of CVD risk from population-based studies. Methods: We followed MOOSE guidelines and systematically searched 6 databases through September 2016 for studies evaluating the association between retinal microvascular abnormalities and white matter hyperintense lesions (WMHI), lacunar infarcts (LI), and cerebral infarctions (CI). Adjusted and unadjusted odds ratios (ORs) and confidence intervals were pooled into the analyses using the DerSimonian and Laird random effects model. Study quality and dissemination biases were assessed and integrated. Results: Thirty-four prospective studies encompassing 84,144 patients were eligible for meta-analysis. After adjustment for vascular risk factors, focal arteriolar narrowing was associated with WMHI (OR, 1.24 [1.01-1.79]), LI (OR, 1.77 [1.14-2.74]), and CI (OR, 1.75 [1.14-2.69]). Venular dilation was significantly associated with LI (OR, 1.46 [1.10-1.93]), whereas retinal hemorrhage was associated with WMHI (OR, 2.23 [1.34-3.70]). Arteriovenous nicking was associated with WMHI (OR, 1.51 [1.22-1.88]) and LI (OR, 1.70 [1.05-2.76]). Any retinopathy exhibited significant association with WMHI, LI, and CI. Heterogeneity was significant ( I 2 >50%) for all syntheses except retinal hemorrhages and WMHI, retinopathy and CI ( I 2 =0.0%) and respectively LI ( I 2 =45.80%). Conclusions: Retinal hemorrhages were most highly associated with WMHI. Focal arteriolar narrowing and retinopathy were associated with WMHI, LI, and CI. Our findings may assist in the development of a noninvasive retinal microvascular tool for routine use in CVD research and clinical practice.

Intravenous recombinant tissue plasminogen activator was first approved for the treatment of acute ischemic stroke in the United States in 1996. Thrombolytic therapy has been proven to be effective in acute ischemic stroke treatment and shown to improve long-term functional outcomes. Its use is associated with an increased risk of symptomatic intracerebral hemorrhage as well as orolingual angioedema. Our goal is to outline the management strategies for these postthrombolysis complications.