Taher, Riad

Introduction: Previous studies in patients with Raynaud’s phenomenon (RP) have found an association between microvascular abnormalities assessed via nail fold capillaroscopy as well as macrovascular peripheral endothelial dysfunction (PED). However, the association between RP and microvascular PED is not yet established. Hypothesis: We hypothesized that patients with RP have greater microvascular PED compared to controls without RP Methods: We performed a retrospective cross-sectional analysis of patients referred to Mayo Clinic between 2006 and 2014 for routine cardiovascular evaluation, and who underwent evaluation of Reactive Hyperemia Peripheral Arterial Tonometry (index < 2 consistent with PED). Patients with RP were identified by chart review. Results: Six hundred sixty six individuals were included in this study (mean age 51.9±13.5 years, 411 (61.3%) women), 637 (95.1%) individuals did not have RP (control group), and 29 (4.3%) had secondary RP. Only 4 patients had primary RP and were excluded from the final analyses. Individuals with secondary RP had a higher frequency of microvascular PED compared to controls ( Figure ). In a multivariate analysis adjusting for age, sex, smoking status, and use of statins we found a significant association between secondary RP and microvascular PED (OR: 2.45; 95% CI 1.13-5.34; P=0.0236) that remained significant in women after stratifying by sex. In a sensitivity analysis, we compared the frequency of PED in 29 patients with secondary RP and 58 controls matched with respect to age, sex, hypertension, dyslipidemia, and diabetes mellitus. Individuals with secondary RP had a higher frequency of microvascular PED compared to the risk factor-matched controls (18/29 [62.1%] vs 18/58 [31.0%], P=0.01). Conclusions: Secondary RP is associated with microvascular PED. Early detection of microvascular PED could help identify individuals with secondary RP who are at risk for developing cardiovascular disease.

Background Peripheral microvascular endothelial dysfunction (PMED) has been linked to an increased risk of cardiovascular events, but there is a lack of information characterizing the predictive value of PMED for future risk of ischemic stroke (IS). Methods and Results This retrospective observational cohort study enrolled 637 patients who underwent non‐invasive microvascular endothelial function assessment using reactive hyperemia peripheral arterial tonometry. Reactive hyperemia peripheral arterial tonometry index ≤2 was defined as PMED. Of 280 patients with PMED, 12 (4.3%) patients developed IS, compared with only 4 (1.1%) of 357 patients without PMED during a median follow‐up of 5.3 years. Patients with PMED had lower IS‐free survival compared with patients without PMED (log‐rank P =0.03). Cox proportional hazard ratio (HR) analyses showed that PMED predicted the incidence of IS, with a HR of 3.43, 95% CI, 1.10–10.63 ( P =0.03); adjusted HR of 3.70, 95% CI, 1.18–11.59 ( P =0.02) after adjusting for sex, smoking history, and atrial fibrillation; adjusted HR of 3.45, 95% CI, 1.11–10.72 ( P =0.03) after adjusting for CHA 2 DS 2 ‐VASc score; adjusted HR of 5.70, 95% CI, 1.40–23.29 ( P =0.02) after adjusting for revised Framingham Stroke Risk Score. Reactive hyperemia peripheral arterial tonometry index improved discrimination of risk for IS after adding reactive hyperemia peripheral arterial tonometry index to CHA 2 DS 2 ‐VASc score and revised Framingham Stroke Risk Score. Conclusions PMED was associated with a >3‐fold increased risk of IS. These findings underscore the concept of the systemic nature of endothelial dysfunction, which could act as a potential marker to predict future risk of IS.

Heart failure is a common debilitating illness, associated with significant morbidity and mortality, rehospitalisation and societal costs. Current guidelines and position statements emphasise the management of patients with overt symptomatic disease, but the increasing prevalence of congestive heart failure underscores the need to identify and manage patients with early left ventricular dysfunction prior to symptom onset. Asymptomatic left ventricular systolic dysfunction (ALVSD), classified as stage B heart failure, is defined as depressed left ventricular systolic function in the absence of clinical heart failure. Early initiation of therapies in patients with presumed ALVSD has been shown to lead to better outcomes. In this article, the authors clarify issues surrounding the definition and natural history of ALVSD, outline clinical tools that may be of value in identifying patients with ALVSD and highlight potential opportunities for future investigations to better address aspects of our understanding of this complex syndrome.

Background The presence of a durable left ventricular assist device ( LVAD ) is associated with increased risk of vasoplegia in the early postoperative period following heart transplantation ( HT ). However, preoperative predictors of vasoplegia and its impact on survival after HT are unknown. We sought to examine predictors and outcomes of patients who develop vasoplegia after HT following bridging therapy with an LVAD . Methods and Results We identified 94 patients who underwent HT after bridging with continuous‐flow LVAD from 2008 to 2018 at a single institution. Vasoplegia was defined as persistent low vascular resistance requiring ≥2 intravenous vasopressors within 48 hours after HT for >24 hours to maintain mean arterial pressure >70 mm Hg. Overall, 44 patients (46.8%) developed vasoplegia after HT . Patients with and without vasoplegia had similar preoperative LVAD , echocardiographic, and hemodynamic parameters. Patients with vasoplegia were significantly older; had longer LVAD support, higher preoperative creatinine, longer cardiopulmonary bypass time, and higher Charlson comorbidity index; and more often underwent combined organ transplantation. In a multivariate logistic regression model, older age (odds ratio: 1.08 per year; P =0.010), longer LVAD support (odds ratio: 1.06 per month; P =0.007), higher creatinine (odds ratio: 3.9 per 1 mg/dL; P =0.039), and longer cardiopulmonary bypass time (odds ratio: 1.83 per hour; P =0.044) were independent predictors of vasoplegia. After mean follow‐up of 4.0 years after HT , vasoplegia was associated with increased risk of all‐cause mortality (hazard ratio: 5.20; 95% CI, 1.71–19.28; P =0.003). Conclusions Older age, longer LVAD support, impaired renal function, and prolonged intraoperative CPB time are independent predictors of vasoplegia in patients undergoing HT after LVAD bridging. Vasoplegia is associated with worse prognosis; therefore, detailed assessment of these predictors can be clinically important.

Aims Cardiovascular health metrics predict the risk not only of cardiovascular diseases but also of several types of cancers. Microvascular endothelial dysfunction can predict future cardiovascular adverse events, but the predictive value of microvascular endothelial dysfunction for future risk of solid-tumor cancer has not been characterized. Methods A total of 488 patients who underwent microvascular endothelial function assessment using reactive hyperemia peripheral arterial tonometry were included in this study. Microvascular endothelial dysfunction was defined as a reactive hyperemia peripheral arterial tonometry index ≤2.0. Results Of 221 patients with a baseline reactive hyperemia peripheral arterial tonometry index ≤2.0, 21 patients (9.5%) were diagnosed with incident solid-tumor cancer during follow-up, whereas of 267 patients with a baseline reactive hyperemia peripheral arterial tonometry index >2.0, 10 patients (3.7%) were diagnosed with incident solid-tumor cancer during follow-up ( p = 0.009). Patients with a reactive hyperemia peripheral arterial tonometry index ≤2.0 had lower solid-tumor cancer-free survival compared to patients with a reactive hyperemia peripheral arterial tonometry index >2.0 (log-rank p = 0.017) (median follow-up 6.0 (3.0–9.1) years). Cox proportional hazard analyses showed that a reactive hyperemia peripheral arterial tonometry index ≤2.0 predicted the incidence of solid-tumor cancer, with a hazard ratio of 2.52 (95% confidence interval 1.17–5.45; p = 0.019) after adjusting for age, sex, and coronary artery disease, 2.83 (95% confidence interval 1.30–6.17; p = 0.009) after adjusting for diabetes mellitus, hypertension, smoking status, and body mass index >30 kg/m2, 2.79 (95% confidence interval 1.21–6.41; p = 0.016) after adjusting for fasting plasma glucose, systolic blood pressure, smoking status (current or former), and body mass index, and 2.43 (95% confidence interval 1.10–5.34; p = 0.028) after adjusting for Framingham risk score. Conclusion Microvascular endothelial dysfunction, as defined by a reactive hyperemia peripheral arterial tonometry index ≤2.0, was associated with a greater than two-fold increased risk of solid-tumor cancer. Microvascular endothelial dysfunction may be a useful marker to predict the future risk of solid-tumor cancer, in addition to its known ability to predict cardiovascular disease. Further research is necessary to develop adequate cancer screening strategies for patients with microvascular endothelial dysfunction.