A pragmatic clinical trial assessing the effect of a targeted notification and clinical support pathway on the diagnostic evaluation and treatment of individuals with left ventricular hypertrophy (NOTIFY-LVH).

BACKGROUND: Electronic health records contain vast amounts of cardiovascular data, including potential clues suggesting unrecognized conditions. One important example is the identification of left ventricular hypertrophy (LVH) on echocardiography. If the underlying causes are untreated, individuals are at increased risk of developing clinically significant pathology. As the most common cause of LVH, hypertension accounts for more cardiovascular deaths than any other modifiable risk factor. Contemporary healthcare systems have suboptimal mechanisms for detecting and effectively implementing hypertension treatment before downstream consequences develop. Thus, there is an urgent need to validate alternative intervention strategies for individuals with preexisting-but potentially unrecognized-LVH. METHODS: Through a randomized pragmatic trial within a large integrated healthcare system, we will study the impact of a centralized clinical support pathway on the diagnosis and treatment of hypertension and other LVH-associated diseases in individuals with echocardiographic evidence of concentric LVH. Approximately 600 individuals who are not treated for hypertension and who do not have a known cardiomyopathy will be randomized. The intervention will be directed by population health coordinators who will notify longitudinal clinicians and offer to assist with the diagnostic evaluation of LVH. Our hypothesis is that an intervention that alerts clinicians to the presence of LVH will increase the detection and treatment of hypertension and the diagnosis of alternative causes of thickened myocardium. The primary outcome is the initiation of an antihypertensive medication. Secondary outcomes include new hypertension diagnoses and new cardiomyopathy diagnoses. The trial began in March 2023 and outcomes will be assessed 12 months from the start of follow-up. CONCLUSION: The NOTIFY-LVH trial will assess the efficacy of a centralized intervention to improve the detection and treatment of hypertension and LVH-associated diseases. Additionally, it will serve as a proof-of-concept for how to effectively utilize previously collected electronic health data to improve the recognition and management of a broad range of chronic cardiovascular conditions. TRIAL REGISTRATION: NCT05713916.

Coronary microvascular dysfunction, left ventricular remodeling, and clinical outcomes in aortic stenosis.

BACKGROUND: We investigated role of coronary microvascular disease (CMD) in maladaptive LV remodeling and prognosis in patients with aortic sclerosis or stenosis and no overt CAD. METHODS: This was a retrospective cohort study of patients with aortic sclerosis or stenosis, normal myocardial perfusion and LV ejection fraction (EF) > 50% (n = 43) and matched controls without AS (n = 43). PET and echocardiograms were performed within 1 year of each other. Myocardial perfusion and myocardial flow reserve (MFR) were quantified using PET imaging. LV structure and function, including global longitudinal strain (GLS), were quantified by transthoracic echocardiography. RESULTS: Global MFR declined with increasing AS severity (P = 0.04). Probability of impaired MFR increased with severity of adverse LV remodeling (OR 1.88, CI 1.03 to 3.41, P =0.04). Reduced MFR associated with impaired GLS (r = - 0.29, P = 0.002) and associated with reduced MACE-free survival at 7.27 years median follow-up. Adjusted annualized rate of MACE was highest in those with impaired GLS and MFR and lowest in those with normal GLS and MFR (30.99% vs 1.86%, P =0.002). CONCLUSION AND RELEVANCE: In patients with AS and no overt CAD, impaired MFR associates with adverse LV remodeling and subclinical LV mechanical dysfunction, and is a marker increased clinical risk.

Patent Foramen Ovale and Stroke.

A patent foramen ovale (PFO) is common and found in nearly 25% of healthy individuals. The majority of patients with PFO remain asymptomatic and they are not at increased risk for developing a stroke. The presence of PFO, however, has been found to be higher in patients with cryptogenic stroke, suggesting there may be a subset of patients with PFO who are indeed at risk for stroke. Paradoxical embolization of venous thrombi through the PFO, which then enter the arterial circulation, is hypothesized to account for this relationship. Although aerated-saline transesophageal echocardiography is the gold standard for diagnosis, aerated-saline transthoracic echocardiography and transcranial Doppler are often used as the initial diagnostic tests for detecting PFO. Patients with cryptogenic stroke and PFO are generally treated with antiplatelet therapy in the absence of another condition for which anticoagulation is necessary. Based on the findings of 3 large randomized clinical trials, current consensus guidelines do not recommend percutaneous closure, though this is an area of controversy. The following review discusses the relationship of PFO and cryptogenic stroke, focusing on the epidemiology, pathophysiological mechanisms, diagnostic tools, associated clinical/anatomic factors and treatment. (Circ J 2016; 80: 1665-1673).

Oral hygiene and infective endocarditis: a case control study.

OBJECTIVE: To determine if oral hygiene is associated with infective endocarditis (IE) among those at moderate risk for IE. STUDY DESIGN: This is a case control study of oral hygiene among hospitalized patients with IE (cases) and outpatients with heart valve disease but without IE (controls). The primary outcome was the mean dental calculus index. Secondary outcomes included other measures of oral hygiene and periodontal disease (e.g., dental plaque, gingivitis) and categorization of blood culture bacterial species in case participants. RESULTS: The 62 case participants had 53% greater mean dental calculus index than the 119 control participants (0.84, 0.55, respectively; difference = 0.29, 95% CI: 0.11, 0.48; P = .002) and 26% greater mean dental plaque index (0.88, 0.70, respectively; difference = 0.18, 95% CI: 0.01.0.36; P = .043). Overall, cases reported fewer dentist and dental hygiene visits (P = .013) and fewer dental visits in the 12 weeks before enrollment than controls (P = .007). Common oral bacteria were identified from blood cultures in 27 of 62 cases (44%). CONCLUSIONS: These data provide evidence to support and strengthen current American Heart Association guidance that those at risk for IE can reduce potential sources of IE-related bacteremia by maintaining optimal oral health through regular professional dental care and oral hygiene procedures.

Association Between Peripheral Versus Central Access for Alternative Access Transcatheter Aortic Valve Replacement and Mortality and Stroke: A Report From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.

BACKGROUND: In some patients, the alternative access route for transcatheter aortic valve replacement (TAVR) is utilized because the conventional transfemoral approach is not felt to be either feasible or optimal. However, accurate prognostication of patient risks is not well established. This study examines the associations between peripheral (transsubclavian/transaxillary, and transcarotid) versus central access (transapical and transaortic) in alternative access TAVR and 30-day and 1-year end points of mortality and stroke for all valve platforms. METHODS: Using data from The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry with linkage to Medicare claims, patients who underwent alternative access TAVR from June 1, 2015 to June 30, 2018 were identified. Adjusted and unadjusted Cox proportional hazards modeling were performed to determine the association between alternate access TAVR site and 30-day and 1-year end points of mortality and stroke. RESULTS: Of 7187 alternative access TAVR patients, 3725 (52%) had peripheral access and 3462 (48%) had central access. All-cause mortality was significantly lower in peripheral access versus central access group at in-hospital and 1 year (2.9% versus 6.3% and 20.3% versus 26.6%, respectively), but stroke rates were higher (5.0% versus 2.8% and 7.3% versus 5.5%, respectively; all P<0.001). These results persisted after 1-year adjustment (death adjusted hazard ratio, 0.72 [95% CI, 0.62-0.85] and stroke adjusted hazard ratio, 2.92 [95% CI, 2.21-3.85]). When broken down by individual subtypes, compared with transaxillary/subclavian access patients, transapical, and transaortic access patients had higher all-cause mortality but less stroke (P<0.05). CONCLUSIONS: In this real-world, contemporary, nationally representative benchmarking study of alternate access TAVR sites, peripheral access was associated with favorable mortality and morbidity outcomes compared with central access, at the expense of higher stroke. These findings may allow for accurate prognostication of risk for patient counseling and decision-making for the heart team with regard to alternative access TAVR.

Association of Myocardial Blood Flow Reserve With Adverse Left Ventricular Remodeling in Patients With Aortic Stenosis: The Microvascular Disease in Aortic Stenosis (MIDAS) Study.

Importance: Impaired myocardial flow reserve (MFR) and stress myocardial blood flow (MBF) on positron emission tomography (PET) myocardial perfusion imaging may identify adverse myocardial characteristics, including myocardial stress and injury in aortic stenosis (AS). Objective: To investigate whether MFR and stress MBF are associated with LV structure and function derangements, and whether these parameters improve after aortic valve replacement (AVR). Design, Setting, and Participants: In this single-center prospective observational study in Boston, Massachusetts, from 2018 to 2020, patients with predominantly moderate to severe AS underwent ammonia N13 PET myocardial perfusion imaging for myocardial blood flow (MBF) quantification, resting transthoracic echocardiography (TTE) for assessment of myocardial structure and function, and measurement of circulating biomarkers for myocardial injury and wall stress. Evaluation of health status and functional capacity was also performed. A subset of patients underwent repeated assessment 6 months after AVR. A control group included patients without AS matched for age, sex, and summed stress score who underwent symptom-prompted ammonia N13 PET and TTE within 90 days. Exposures: MBF and MFR quantified on ammonia N13 PET myocardial perfusion imaging. Main Outcomes and Measures: LV structure and function parameters, including echocardiographic global longitudinal strain (GLS), circulating high-sensitivity troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), health status, and functional capacity. Results: There were 34 patients with AS (1 mild, 9 moderate, and 24 severe) and 34 matched control individuals. MFR was independently associated with GLS and LV ejection fraction, (ß,-0.31; P = .03; ß, 0.41; P = .002, respectively). Stress MBF was associated with hs-cTnT (unadjusted ß, -0.48; P = .005) and log NT-pro BNP (unadjusted ß, -0.37; P = .045). The combination of low stress MBF and high hs-cTnT was associated with higher interventricular septal thickness in diastole, relative wall thickness, and worse GLS compared with high stress MBF and low hs-cTnT (12.4 mm vs 10.0 mm; P = .008; 0.62 vs 0.46; P = .02; and -13.47 vs -17.11; P = .006, respectively). In 9 patients studied 6 months after AVR, mean (SD) MFR improved from 1.73 (0.57) to 2.11 (0.50) (P = .008). Conclusions and Relevance: In this study, in AS, MFR and stress MBF were associated with adverse myocardial characteristics, including markers of myocardial injury and wall stress, suggesting that MFR may be an early sensitive marker for myocardial decompensation.

Ajulemic acid, a synthetic cannabinoid, increases formation of the endogenous proresolving and anti-inflammatory eicosanoid, lipoxin A4.

Ajulemic acid (AjA), a synthetic nonpsychoactive cannabinoid, and lipoxin A(4) (LXA(4)), an eicosanoid formed from sequential actions of 5- and 15-lipoxygenases (LOX), facilitate resolution of inflammation. The purpose of this study was to determine whether the ability of AjA to limit the progress of inflammation might relate to an increase in LXA(4), a known anti-inflammatory and proresolving mediator. Addition of AjA (0-30 microM) in vitro to human blood and synovial cells increased production of LXA(4) (ELISA) 2- to 5-fold. Administration of AjA to mice with peritonitis resulted in a 25-75% reduction of cells invading the peritoneum, and a 7-fold increase in LXA(4) identified by mass spectrometry. Blockade of 12/15 LOX, which leads to LXA(4) synthesis via 15-HETE production, reduced (>90%) the ability of AjA to enhance production of LXA(4) in vitro. These results suggest that AjA and other agents that increase endogenous compounds that facilitate resolution of inflammation may be useful for conditions characterized by inflammation and tissue injury.

A Tight Squeeze: Focal Tamponade and Obstructive Shock From Esophageal Stenting.

Cardiac tamponade is a rare cause of shock in the medical intensive care unit. This paper describes the case of a focal cardiac tamponade caused by compression of the left atrium due to an esophageal stent. Echocardiography yielded a diagnosis when other diagnostic methods did not. (Level of Difficulty: Advanced.).

Design and synthesis of benzo-lipoxin A4 analogs with enhanced stability and potent anti-inflammatory properties.

A new class of chemically and metabolically stable lipoxin analogs featuring a replacement of the tetraene unit of native LXA(4) with a substituted benzo-fused ring system have been designed and studied. These molecules were readily synthesized via a convergent synthetic route involving iterative palladium-mediated cross-coupling, and exhibit enhanced chemical stability, as well as resistance to metabolic inactivation via eicosanoid oxido-reductase. These new LX analogs were evaluated in a model of acute inflammation and were shown to exhibit potent anti-inflammatory properties, significantly decreasing neutrophil infiltration in vivo. The most potent among these was compound 9 (o-[9,12]-benzo-15-epi-LXA(4) methyl ester. Taken together, these findings help identify a new class of stable and easily prepared LX analogs that may serve as novel tools and as promising leads for new anti-inflammatory agents with improved therapeutic profile.

Epidemiology, anatomy, pathophysiology and clinical evaluation of functional tricuspid regurgitation.

Tricuspid regurgitation (TR) is commonly encountered in the management of patients with a variety of cardiovascular diseases. Primary TR is the result of structural abnormalities of the valve or chordal attachments whereas functional TR results from alterations in right ventricular (RV) or right atrial (RA) size, shape or function. The vast majority of TR cases seen in practice are functional in nature and usually results from left-sided heart disease (e.g., mitral valve disease, left ventricular (LV) systolic dysfunction) and/or pulmonary vascular disease, though it also manifests in the presence of isolated chronic atrial fibrillation (AF). The relationships among the tricuspid leaflets, annulus, chordal attachments and papillary muscles are critical to normal valve function. Disruption of these interactions through annular dilation and apical displacement of the papillary muscles underlies the pathophysiology of functional TR. Two-dimensional transthoracic echocardiography (2D-TTE) is the primary modality used to assess TR. In situations where 2D-TEE is limited, 3D-TTE and transesophageal echocardiography (TEE), multidetector computed tomography (CT) and cardiac magnetic resonance imaging (MRI) can provide additional information. Classification schemes have been proposed that focus not only on the severity of TR, but also on annular dilation and the mode of leaflet coaptation. Despite often being referred to as the "forgotten valve," there is increasing evidence that functional TR is prognostically significant and may warrant intervention. Appropriate patient selection for and timing of intervention are important clinical tasks that require a comprehensive understanding of the pathophysiology and natural history of functional TR.

Patent foramen ovale.

Patent foramen ovale (PFO) is the most common congenital heart abnormality of fetal origin and is present in approximately ∼25% of the worldwide adult population. PFO is the consequence of failed closure of the foramen ovale, a normal structure that exists in the fetus to direct blood flow directly from the right to the left atrium, bypassing the pulmonary circulation. PFO has historically been associated with an increased risk of stroke, the mechanism of which has been attributed to the paradoxical embolism of venous thrombi that shunt through the PFO directly to the left atrium. However, several studies have failed to show an increased risk of stroke in asymptomatic patients with a PFO, and the risk of stroke recurrence is low in patients who have had a stroke that may be attributed to a PFO. With the advent of transoesophageal and transthoracic echocardiography, as well as transcranial Doppler, a PFO can be routinely detected in clinical practice. Medical treatment with either antiplatelet or anticoagulation therapy is recommended. At the current time, closure of the PFO by percutaneous interventional techniques does not appear to reduce the risk of stroke compared to conventional medical treatment, as shown by three large clinical trials. Considerable controversy remains regarding the optimal treatment strategy for patients with both cryptogenic stroke and PFO. This Primer discusses the epidemiology, mechanisms, pathophysiology, diagnosis, screening, management and effects on quality of life of PFO.