Intramural course We are deeply saddened by the passing of Dr Paolo Angelini, an esteemed cardiologist, ground-breaking researcher, and beloved friend, on July 29, 2023. He departed from us at the age of 81, leaving behind a legacy of remarkable advancements in cardiovascular medicine for more than half a century. Born in Italy, Dr Angelini began his distinguished journey in medicine by earning his medical degree from the prestigious University of Milan in 1966. His interest in cardiology propelled him to pursue a residency at the National Institute of Cardiology in Mexico City, Mexico, under theAbbreviations and Acronyms
The clinical approach to undifferentiated shock in critically ill patients should be revised to use modern, point-of-care tools that are readily available. With the increasing availability of 2-dimensional ultrasonography and advanced Doppler capabilities, a quick, simplified, and integrated stepwise approach to shock using critical care echocardiography is proposed. Evidence supports the feasibility and usefulness of critical care echo-cardiography in enhancing diagnostic accuracy for shock, but there is a lack of systematic application of the technology in patients with undifferentiated shock. The proposed approach begins with the use of noninvasive ultrasonography with pulsed-wave Doppler capability to determine the flow state by measuring the velocity time integral of the left ventricular outflow tract. This narrative review explores the use left ventricular outflow tract velocity time integral, velocity time integral variation, limited visceral organ Doppler, and lung ultrasonography as a systematic approach for patients with undifferentiated shock.Abstract
Cardiovascular disease is the leading cause of death and disability worldwide. Early detection and treatment of cardiovascular disease are crucial for patient survival and long-term health. Despite advances in cardiovascular disease biomarkers, the prevalence of cardiovascular disease continues to increase worldwide as the global population ages. To address this problem, novel biomarkers that are more sensitive and specific to cardiovascular diseases must be developed and incorporated into clinical practice. Exosomes are promising biomarkers for cardiovascular disease. These small vesicles are produced and released into body fluids by all cells and carry specific information that can be correlated with disease progression. This article reviews the advantages and limitations of existing biomarkers for cardiovascular disease, such as cardiac troponin and cytokines, and discusses recent evidence suggesting the promise of exosomes as cardiovascular disease biomarkers.Abstract
This report highlights survival and the patient’s perspective after prolonged venovenous extracorporeal membrane oxygenation (ECMO) for COVID-19–related respiratory failure. A 36-year-old man with COVID-19 presented with fever, anosmia, and hypoxia. After respiratory deterioration necessitating intubation and lung-protective ventilation, he was referred for ECMO. After 3 days of conventional venovenous ECMO, he required multiple creative cannulation configurations. Adequate sedation and recurrent bradycardia were persistent challenges. After 149 consecutive days of ECMO, he recovered native lung function and was weaned from mechanical ventilation. This represents the longest-duration ECMO support in a survivor of COVID-19 yet reported. Necessary strategies included unconventional cannulation and flexible anticoagulation.Abstract
Left sinus of Valsalva aneurysms are extremely rare. Concomitant aortic valve regurgitation is a comorbidity in this pathology. This case report summarizes successful surgical treatment with aortic root replacement with a modified Bentall procedure in a 49-year-old female patient who had an unruptured huge left sinus of Valsalva aneurysm with severe aortic valve regurgitation. The intraoperative assessment showed severe adhesion between the left main trunk of the coronary artery and the left sinus of Valsalva aneurysm, and meticulous adhesion detachment was required.Abstract
Thrombotic and bleeding complications are major causes of morbidity and mortality in patients with polycythemia vera, who predominantly present with an alteration in the JAK2 gene. Because of their hypercoagulable state and risk of hemorrhage, patients with polycythemia vera who present with an acute myocardial infarction pose a challenge to physicians. This case report describes the presentation and treatment of a Hispanic patient with JAK2 V617F–negative primary polycythemia who developed cardiac arrest and ST-segment elevation myocardial infarction owing to complete occlusion of the left anterior descending artery as well as bleeding complications and postmyocardial pericarditis.Abstract
A 64-year-old man with interstitial pulmonary fibrosis and a small patent foramen ovale with right-to-left shunting underwent bilateral lung transplant without closure of the patent foramen ovale. Postoperatively, the patient remained persistently hypoxemic with partial response to high-flow oxygen. Investigations revealed the presence of a large patent foramen ovale with right-to-left shunting on echocardiography and a shunt fraction of 21% on cardiac catheterization. Two months after the lung transplantation, primary surgical repair of the patent foramen ovale was performed with immediate improvement in oxygenation. Three years postoperatively, the patient remained oxygen independent.Abstract
Patients with pulmonary arterial hypertension have quality-of-life limitations, decreased exercise capacity, and poor prognosis if the condition is left untreated. Standard exercise testing is routinely performed to evaluate patients with pulmonary arterial hypertension but may be limited in its ability to monitor activity levels in daily living. To evaluate the validity of the commercial Fitbit Charge HR as a tool to assess real-time exercise capacity as compared with standard exercise testing. Ambulatory pediatric and adult patients were enrolled and given a Fitbit with instructions to continuously wear the device during waking hours. Patients underwent a 6-minute walk test, cardiopulmonary exercise test, and a 36-Item Short Form Health Survey on the day of enrollment and follow-up. Twenty-seven ambulatory patients with pulmonary arterial hypertension were enrolled, and 21 had sufficient data for analyses (median age, 25 years [range, 13-59 years]; 14 female participants). Daily steps measured by the Fitbit had a positive correlation with 6-minute walk distance (r = 0.72, P = .03) and an inverse trend with World Health Organization functional class. On the 36-Item Short Form Health Survey, 77% of patients reported improvement in vitality (P = .055). At follow-up, there was a strong correlation between number of steps recorded by Fitbit and role limitations because of physical problems (r = 0.88, P = .02) and weaker correlations with other quality-of-life markers. The findings of this pilot study suggest activity monitors may have potential as a simple and novel method of assessing longitudinal exercise capacity and activity levels in patients with pulmonary hypertension. Further study in larger cohorts of patients is warranted to determine which accelerometer measures correlate best with outcomes.Abstract
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Patient-prosthesis mismatch (PPM) may impair functional capacity and survival after aortic valve replacement. This study aimed to investigate the impact of PPM on long-term survival and quality of life after mechanical and biological aortic valve replacement. This study included 595 consecutive patients who had undergone isolated aortic valve replacement. Patients were divided into 2 groups according to prosthesis type. The baseline and operative characteristics, survival rates, complications, and quality of life of the groups with and without PPM were compared for up to 6 years. The PPM calculation was performed using the effective orifice area value provided by the manufacturer divided by the patient's body surface area. The moderate to severe PPM rates were 69.8% and 3.7% after biological and mechanical prosthesis implantation, respectively. Mean survival for patients in the biological group who had PPM was statistically significantly shorter (50.2 months [95% CI, 45.2-55.3]) than for patients in the biological group without PPM (60.1 months [95% CI, 55.7-64.4]; P = .04). In the mechanical prosthesis group, there was no difference in mean survival between the subgroup with PPM (66.6 months [95% CI, 58.3-74.9]) and the subgroup without PPM (64.9 months [95% CI, 62.6-67.2]; P = .50). A quality-of-life questionnaire's scores did not differ between the groups. Mismatch is common after biological valve implantation and statistically significantly affects long-term survival and quality of life. If the risk of PPM after implantation of a biological prosthesis is suspected, adopting strategies to avoid PPM at the time of surgery is warranted.Abstract
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Data on race-related differences in the clinical outcomes of Takotsubo syndrome are limited, particularly for Black patients. This study aimed to assess whether race and sex may have an additional impact on the inpatient mortality of patients with Takotsubo syndrome. A total of 4,628 patients from the United States' National Inpatient Sample from 2012 to 2016 were identified; propensity score analysis revealed a similar propensity score between Black patients (n = 2,314) and White patients (n = 2,314), which was used to balance observed covariates. Sex and age distributions were identical between the 2 groups. The groups were also similar in baseline characteristics, including cardiovascular risk factors. White patients were compared with Black patients on in-hospital outcomes and inpatient mortality. A logistic regression analysis was conducted to measure the difference in mortality based on race and sex. Compared with White patients, Black patients had a higher percentage of in-hospital complications, including cerebrovascular accidents (4.9% vs 2.5%, P ≤ .01), acute kidney injury (25% vs 19%, P ≤ .01); longer lengths of stay (8 vs 7 days, P ≤ .01); and higher inpatient mortality (6.1% vs 4.5%, P < .01). When analysis was conducted with race and sex combined, inpatient mortality was higher among Black men than among White women (odds ratio, 2.7 [95% CI, 1.80-3.95]; P ≤ .01). This study showed that Black patients with Takotsubo syndrome have higher in-hospital complications and inpatient mortality rates. When race and sex were combined, inpatient mortality was significantly higher among Black men than among either White men and women or Black women.Abstract
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Postoperative atrial fibrillation (POAF) frequently complicates cardiac surgery. Predicting POAF can guide interventions to prevent its onset. This study assessed the incidence, risk factors, and related adverse outcomes of POAF after cardiac surgery. A cohort of 1,606 patients undergoing cardiac surgery at a tertiary referral center was analyzed. Postoperative AF was defined based on the Society of Thoracic Surgeons’ criteria: AF/atrial flutter after operating room exit that either lasted longer than 1 hour or required medical or procedural intervention. Risk factors for POAF were evaluated, and the performance of established risk scores (POAF, HATCH, COM-AF, CHA2DS2-VASc, and Society of Thoracic Surgeons risk scores) in predicting POAF was assessed using discrimination (area under the receiver operator characteristics curve) analysis. The association of POAF with secondary outcomes, including length of hospital stay, ventilator time, and discharge to rehabilitation facilities, was evaluated using adjusted linear and logistic regression models. The incidence of POAF was 32.2% (n = 517). Patients who developed POAF were older, had traditional cardiovascular risk factors and higher Society of Thoracic Surgeons risk scores, and often underwent valve surgery. The POAF risk score demonstrated the highest area under the receiver operator characteristics curve (0.65), but risk scores generally underperformed. Postoperative AF was associated with extended hospital stays, longer ventilator use, and higher likelihood of discharge to rehabilitation facilities (odds ratio, 2.30; 95% CI, 1.73-3.08). This study observed a high incidence of POAF following cardiac surgery and its association with increased morbidity and resource utilization. Accurate POAF prediction remains elusive, emphasizing the need for better risk-prediction methods and tailored interventions to diminish the effect of POAF on patient outcomes.Abstract
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external iliac artery posterior tibial This case involves a 73-year-old man with chronic limb-threatening ischemia who presented for a left lower extremity angiogram, which demonstrated high-grade stenosis of the distal superficial femoral artery and high-grade stenosis at the proximal anterior tibial artery with flow to the foot and collaterals to the posterior tibial (PT) artery. A long 7F sheath was only able to be advanced into the external iliac artery (EIA) during the procedure. Lesions were treated with balloon angioplasty and stent of the superficial femoral artery and angioplasty of the anterior tibialAbbreviations and Acronyms
Case Description
heart failure with preserved ejection fraction interleukin left ventricular sodium-glucose cotransporter-2 Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome characterized by elevated left ventricular (LV) stiffness and filling pressures, despite normal or near-normal EFs. It accounts for approximately half of all HF cases and has become increasingly prevalent with an aging population.1 In contrast to HF with reduced EF, HFpEF is less understood, and options for effective treatment are limited.2 Recent evidence suggests that systemic inflammation plays a pivotal role in HFpEF pathophysiology.3Abbreviations and Acronyms
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cardiac stem cell Adult heart regeneration is currently an active and controversial area of biomedical research, representing a relatively new field within cardiac biology.1 Given the widespread occurrence and poor outlook of heart failure,1 the potential impact of successful strategies for regenerating the human heart cannot be underestimated. The biology underlying the regenerative process of the heart is highly complex, however, and the existence of compelling data demonstrating effective heart regeneration has generated fascination, contentious debate, and scientific scandal.1 Although myocardial regeneration involves the replenishment of various cell types,Abbreviations and Acronyms
Introduction
bone marrow mononuclear cells heart failure with reduced ejection fraction Following advances in prevention and management, clinical outcomes for patients with ischemic heart disease—in particular, myocardial infarction—have substantially improved. There remains, however, an unmet need for novel therapies to better manage heart failure with reduced ejection fraction (HFrEF) in patients with a prior myocardial infarction beyond that afforded by current lifestyle modification and pharmacologic management. Cell-based therapies offer a promise to address this need. Although limited in numbers and duration of follow-up, meta-analyses by the Cochrane Group1 and others support theAbbreviations and Acronyms
Introduction
heart failure intravenous left ventricular magnetic resonance imaging mesenchymal stromal cell Cell therapy is a potentially useful approach to treating heart failure (HF) secondary to chronic ischemic cardiomyopathy (ischemic HF).1 Despite controversy,2 the preclinical data in the field of cell therapy are clear: Although transplanted cells do not regenerate cardiomyocytes, preclinical studies have consistently shown that they improve cardiac performance.1,2 Bone marrow–derived mesenchymal stromal cells (MSCs) are among the most promising cell types in the preclinical arena1 and for patients withAbbreviations and Acronyms
Introduction
Understanding the dynamics of cardiomyocyte ploidy is of paramount importance for deciphering the cellular mechanisms propelling cardiac development,1 regeneration,2 and disease.3 Cardiomyocytes possess diverse ploidy levels that can vary significantly among the cell population. Both polyploidization and ploidy reduction are well documented in liver hepatocytes in response to injury and repair, but these processes are poorly understood in the context of the heart. To address this gap in scientific understanding, a novel approach using single-cell, flow cytometry–based imaging and software-driven machine learning algorithms has been employed. The existing technical limitations associatedIntroduction
Current Limitations
left ventricular Regenerative therapies are under evaluation in clinical trial settings to assess their potential in fostering the structural and functional recovery of failing myocardium. Notably, however, a low and unreliable level of cell retention after treatment delivery has hindered adequate dosing.1 This shortcoming is a recognized contributor to mixed outcomes in cell-treated patients. This limitation is, in part, related to the highly vascularized, spongelike structure and the heterogenous texture of cardiac tissue. Accordingly, cells—even when directly delivered into the myocardium itself—may escape into the systemic circulation or pericardial space. Cell retention afterAbbreviations and Acronyms
Introduction
cardiac stem/progenitor cells dasatinib and quercetin senescence-associated secretory phenotype “Cell senescence is a detrimental cell state triggered by stressful insults and certain physiological processes” (ie, oxidative stress, reactive oxygen species), whereby damaged cells exit the cell cycle permanently but remain metabolically active.1 A key feature of senescent cells is that they produce and secrete proinflammatory factors, termed the senescence-associated secretory phenotype (SASP). Senescent cells accumulate in all tissues, including the heart, with aging and at etiological sites in multiple chronic diseases. Senescent cells also accumulate in the heart dueAbbreviations and Acronyms
Background
extracellular vesicles pluripotent stem cells Cells used for repairing chronically failing hearts can be broadly divided into 2 categories depending on their lineage commitment. In the category of noncardiac cells, mesenchymal stromal cells remain the most attractive because of their immune-modulatory, anti-inflammatory, and angiogenic properties; they continue to be clinically investigated. The second category includes cardiac-committed cells differentiated from pluripotent stem cells (PSCs), such as embryonic stem cells or induced PSCs. Because they are able to graft to the chronically infarcted myocardium and improve its function, including in nonhuman primates,1,2Abbreviations and Acronyms
Background
adeno-associated virus 9 cardiomyocyte myocardial infarction After a myocardial infarction (MI), scar tissue formation and loss of cardiac muscle negatively affect the heart’s ability to contract, resulting in pathologic remodeling and eventual heart failure (HF). Current paradigms hold that cardiomyocytes (CMs) cannot proliferate and repair the heart after MI. The Hippo signaling pathway is an inhibitory kinase cascade that represses adult CM proliferation and renewal after MI.1 Interestingly, though, neonatal mouse and pig hearts can regenerate within a limited time frame after birth,2–4 and anecdotal reports suggestAbbreviations and Acronyms
Background
