Frank Corrigan

Circadian Variation in Vascular Function and Regenerative Capacity in Healthy Humans

Background Progenitor cells (PCs) are mobilized in response to vascular injury to effect regeneration and repair. Recruitment of PCs requires intact nitric oxide (NO) synthesis by endothelial cells, and their number and activity correlate with cardiovascular disease risk burden and future outcomes. Whereas cardiovascular vulnerability exhibits a robust circadian rhythm, the 24‐hour variation of PCs and their inter‐relation with vascular function remain unknown. We investigated the circadian variation of PCs and vascular function with the hypothesis that this will parallel the pattern observed for cardiovascular events (CVEs). Methods and Results In 15 healthy subjects (9 men, 37±16 years), circulating PCs and vascular function were measured at 8 am, noon, 4 pm, 8 pm, midnight, 4 am (only PCs counts), and 8 am the following day. Circulating PCs were enumerated as mononuclear cells (MNCs; CD45med) that express CD34 as well as CD133, and their activity was assessed as the number of colonies formed by culturing MNCs. Vascular function was evaluated by measurement of endothelium‐dependent, flow‐mediated vasodilation (FMD) of the brachial artery and tonometry‐derived indices of arterial stiffness. Higher CD34+ and CD34+/CD133+ cell counts were observed at 8 pm than any other time of the day (P‐ANOVA=0.038 and <0.001; respectively) and were lowest at 8 am. PC colony formation was highest at midnight (P‐ANOVA=0.045) and lowest in the morning hours. FMD was highest at midnight and lowest at 8 am and 8 pm, and systemic arterial stiffness was greatest at 8 am and lowest at 4 pm and midnight (P‐ANOVA=0.03 and 0.01; respectively). Conclusion A robust circadian variation in PC counts and vascular function occurs in healthy humans and both exhibit an unfavorable profile in the morning hours that parallels the preponderance of CVEs at these times. Whether these changes are precipitated by awakening and time‐dependent physical activity or governed by the endogenous circadian clock needs to be further investigated.

Low testosterone in men predicts impaired arterial elasticity and microvascular function

BACKGROUND A low testosterone level in men is associated with increased adiposity, insulin resistance, and dyslipidemia. Whether low testosterone level is associated with arterial stiffness and endothelial and microvascular dysfunction remains unknown and was investigated in this study. METHODS Serum testosterone was measured in 237 healthy men aged 50 years (SD 12). Endothelial and microvascular function were assessed as brachial artery flow-mediated dilation (FMD) and digital reactive hyperemia index (RHI), respectively. Arterial stiffness was evaluated by tonometry-derived pulse wave velocity (PWV) and central augmentation index (AIX). RESULTS Mean total testosterone level was 16.3 nmol/L (SD 6.11) and 25% of subjects had low levels (<12.0 nmol/L). Testosterone level correlated positively with RHI (r=0.24, p<0.001) and inversely with AIX (r=-0.14, p=0.033) but not with FMD or PWV, indicating impaired microvascular hyperemia and arterial elasticity with lower testosterone levels. After multivariate adjustment for the Framingham Risk Score and weight, testosterone level remained an independent predictor of RHI and AIX (β=0.23, -0.13; p=0.001, 0.04, respectively). CONCLUSION In men with few co-morbidities, lower serum testosterone level is associated with microvascular dysfunction and increased pulse wave reflections, mechanisms by which lower testosterone levels may confer increased cardiovascular risk. Whether normalization of low testosterone level improves vascular function needs further investigation.

Paravalvular Regurgitation after Transcatheter Aortic Valve Replacement: Comparing Transthoracic versus Transesophageal Echocardiographic Guidance

Background: Transcatheter aortic valve replacement (TAVR) is increasingly being performed in cardiac catheterization laboratories using transthoracic echocardiography (TTE) to guide valve deployment. The risk of paravalvular regurgitation (PVR) remains a concern. Methods: We retrospectively reviewed 454 consecutive patients (mean age, 82 ± 8; 58% male) who underwent transfemoral TAVR at Emory Healthcare from 2007 to 2014. Two hundred thirty‐four patients underwent TAVR in the cardiac catheterization laboratory with TTE guidance (TTE‐TAVR; mean Society of Thoracic Surgeons score, 10%), while 220 patients underwent the procedure in the hybrid operating room with transesophageal echocardiography (TEE) guidance (TEE‐TAVR; mean Society of Thoracic Surgeons score, 11%). All patients received an Edwards valve (SAPIEN 55%, SAPIEN‐XT 45%). Clinical and procedural characteristics, echocardiographic parameters, and incidence of PVR were compared. Results: The incidence of at least mild PVR at discharge was comparable between TTE‐TAVR and TEE‐TAVR (33% vs 38%, respectively; P = .326) and did not differ when stratified by valve type. However, in the TTE‐TAVR group, there was a higher incidence of second valve implantation (7% vs 2%; P = .026) and postdilation (38% vs 17%; P < .001) during the procedure. Although not independently associated with PVR at discharge (odds ratio = 1.12; 95% CI, 0.69–1.79), TTE‐TAVR was associated with PVR‐related events: the combined outcome of mild PVR at discharge, intraprocedural postdilation, and second valve insertion (odds ratio = 1.58; 95% CI, 1.01–2.46). There were no significant differences in PVR at 30 days, 6 months, and 1 year between the two groups. Conclusions: TTE‐TAVR in a high‐risk group of patients was associated with increased incidence of intraprocedure PVR‐related events, although it was not associated with higher rates of PVR at follow‐up. Multicenter randomized trials are required to confirm the cost‐effectiveness and safety of TTE‐TAVR. HighlightsMinimalist transthoracic echocardiography (TTE)–guided transcatheter aortic valve replacement (TAVR) is increasingly performed in cardiac catheterization laboratories.Patients undergoing TTE‐TAVR were more likely to receive balloon postdilation and second valve placement.Paravalvular regurgitation at discharge was not increased with TTE‐guided TAVR.

Ostial right coronary chronic total occlusion: Transesophageal echocardiographic guidance for retrograde aortic re‐entry

As antegrade options are limited, intervention upon the ostial right coronary artery (RCA) chronic total occlusion (CTO) warrants a retrograde approach. Landmarks for an aggressive approach are concerning as passage of stiff guidewires or electrocautery near the RCA ostium may result in wire passage into structures other than the aorta. We report the first use of transesophageal echocardiography (TEE) to assist retrograde passage of a guidewire into the aorta. For the ostial RCA CTO, TEE guidance may be considered to assist retrograde passage of aggressive guidewires into the aorta.

Images in InterventionGrabbing the Transcatheter Valve Skirt: Bail-Out Technique for Valve Embolization During Valve-in-Valve Transcatheter Mitral Valve Replacement

An 80-year-old man with history of coronary artery bypass grafting and mitral annuloplasty with a semirigid Physio-1 ring 30 mm (Edwards Lifesciences, Irvine, California) for ischemic mitral regurgitation was referred to our hospital because of worsening shortness of breath. An echocardiogram

Anatomical risk models for paravalvular leak and landing zone complications for balloon-expandable transcatheter aortic valve replacement

Though several anatomical characteristics have been reported separately as risk factors for paravalvular leak (PVL) and landing zone (LZ) complications after transcatheter aortic valve replacement (TAVR), multivariate risk models are needed.

Polyarticular Gout Flare Masquerading as Sepsis

In patients with poorly controlled gout, polyarticular gout attacks occur more frequently than in those with less advanced disease. Such flares can induce a systemic inflammatory response syndrome that may be misdiagnosed as sepsis. Distinguishing these two entities, which often present with similar findings, is challenging. We present a case of an acute polyarticular gout attack masquerading as sepsis and the clinical pitfalls associated with this diagnosis.

Contemporary evaluation of mitral regurgitation – 3D echocardiography, cardiac magnetic resonance, and procedural planning

ABSTRACT Introduction: Mitral regurgitation is one of the more common forms of valvular heart disease. Given the expansion of therapies for structural heart disease, new therapies for mitral regurgitation are emerging. An accurate description and classification of mitral disease is important to understand pathology and provide recommendations for therapy. Areas covered: In the modern evaluation of mitral regurgitation, 3-dimensional echocardiography (3DE) and cardiac magnetic resonance imaging (CMR) play important roles which overcome the prior limitations of 2-dimensional echocardiography. Specifically, an advanced evaluation with these techniques allows accurate characterization of the anatomic etiology of mitral regurgitation and quantification of severity. Furthermore, the role of 3DE during intraprocedural guidance, ‘interventional echocardiography,’ is expanding. Expert commentary: In our review, we demonstrate a complete diagnostic evaluation of mitral valve dysfunction by 3DE and CMR and describe current implications for invasive therapy and procedural guidance.

OBSTRUCTIVE SLEEP APNEA IS ASSOCIATED WITH INCREASED SEVERITY OF CORONARY ARTERY DISEASE AND WORSE CARDIOVASCULAR OUTCOMES

Asrac Caeor: 2. Chroc CAD/Sale Ischemc Hear Dsease: Clcalreseao Numer: 120-398Auhors: Nicholas A. Mantini, Danny Eapen, Frank Corrigan, Suliman Alradawi, Pankaj Manocha, Riyaz Patel, Muhammad Hammadah, Mohammad Tarek Kabbany, Ravi Nanjundappa, Rostam Zafari, James C. Lee, Hatem Al Kassem, Revanth Yendamuri, Ying X. Liu, Naureen Farook, Aliy M. Ahmed, Mohammad S. Qadir, Laurence Sperling, Arshed Quyyumi, Emory University School of Medicine, Atlanta, GA, USAIntroduction: sruce sleep apea (SA) s assocae wh oxae sress, rs acors clu hpereso, a wh ar presece o coroar arer sease (CAD). Howeer, wheher SA corues o he seer o CAD a o uure aerse ees paes wh CAD remas uow. We hpohesze ha SA wll e assocae wh reaer seer o coroar aheroscleross a worse caroascular oucomes.Methods: I a case-corol su o 893 paes recrue o he Emor Carolo oa who uerwe coroar aoraph, 402 ha ocumee SA a 491 were ree o SA. Seer o CAD was ocumee us he Ges score. aes were ollowe-up or 2.5 ears or prospece occurrece o maor aerse caroascular ees eie as eah, mocaral arco (MI) or reascularzao. Mularae lear reresso a Cox proporoal hazar moels were perorme o eerme he assocaos o SA wh CAD seer a oucomes.Results: Aer mularae ausme or ae, eer, smo, slpema, aees, o mass ex (MI), mecao, MI/SA eraco a eeco raco, SA remae a epee precor o hher Ges coroar seer score (p=.00). resece o SA was assocae wh a 3.4 (CI 1.48-8.2, p=0.007) reaer hazar or uure aerse CVD oucomes. Us Cox proporoal moel, here was worsee sural or hose wh SA compare o hose whou (p=.044).Conclusions: I uals wh ow CAD or a hh rs or aheroscleross, presece o SA s assocae wh a reaer seer o CAD a s prece o worse caroascular oucomes.

Coronary and Peripheral Vasomotor Responses to Mental Stress

Background Coronary microvascular dysfunction may contribute to myocardial ischemia during mental stress (MS). However, the role of coronary epicardial and microvascular function in regulating coronary blood flow (CBF) responses during MS remains understudied. We hypothesized that coronary vasomotion during MS is dependent on the coronary microvascular endothelial function and will be reflected in the peripheral microvascular circulation. Methods and Results In 38 patients aged 59±8 years undergoing coronary angiography, endothelium‐dependent and endothelium‐independent coronary epicardial and microvascular responses were measured using intracoronary acetylcholine and nitroprusside, respectively, and after MS induced by mental arithmetic testing. Peripheral microvascular tone during MS was measured using peripheral arterial tonometry (Itamar Inc, Caesarea, Israel) as the ratio of digital pulse wave amplitude compared to rest (peripheral arterial tonometry ratio). MS increased the rate‐pressure product by 22% (±23%) and constricted epicardial coronary arteries by −5.9% (−10.5%, −2.6%) (median [interquartile range]), P=0.001, without changing CBF. Acetylcholine increased CBF by 38.5% (8.1%, 91.3%), P=0.001, without epicardial coronary diameter change (0.1% [−10.9%, 8.2%], P=not significant). The MS‐induced CBF response correlated with endothelium‐dependent CBF changes with acetylcholine (r=0.38, P=0.03) but not with the response to nitroprusside. The peripheral arterial tonometry ratio also correlated with the demand‐adjusted change in CBF during MS (r=−0.60, P=0.004), indicating similarity between the microcirculatory responses to MS in the coronary and peripheral microcirculation. Conclusions The coronary microvascular response to MS is determined by endothelium‐dependent, but not endothelium‐independent, coronary microvascular function. Moreover, the coronary microvascular responses to MS are reflected in the peripheral microvascular circulation.