Kenta Nakamura

iPS Cell Modeling of Cardiometabolic Diseases

Cardiometabolic diseases encompass simple monogenic enzyme deficiencies with well-established pathogenesis and clinical outcomes to complex polygenic diseases such as the cardiometabolic syndrome. The limited availability of relevant human cell types such as cardiomyocytes has hampered our ability to adequately model and study pathways or drugs relevant to these diseases in the heart. The recent discovery of induced pluripotent stem (iPS) cell technology now offers a powerful opportunity to establish translational platforms for cardiac disease modeling, drug discovery, and pre-clinical testing. In this article, we discuss the excitement and challenges of modeling cardiometabolic diseases using iPS cell and their potential to revolutionize translational research.

Treatment of Hypertension in Coarctation of the Aorta

Opinion statementThe treatment of hypertension in coarctation of the aorta (CoA) is ideally managed by early surgical or transcatheter repair to reduce the risk of irreversible aortopathy and refractory hypertension, in addition to other associated sequelae including premature coronary artery disease; stroke; aortic aneurysm, dissection, and rupture; infective endocarditis; and heart failure. The choice of surgical or transcatheter repair is dependent on individual patient considerations. Medical therapy for hypertension due to CoA parallels treatment of essential hypertension with beta blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers as first-line agents.

Percutaneous closure of acute aorto‐right ventricular fistula following transcatheter bicuspid aortic valve replacement

We report a case of acute aorto‐right ventricular fistula following transcatheter bicuspid aortic valve replacement and subsequent percutaneous closure. The diagnosis and treatment of this rare complication is illustrated through multi‐modality imaging. We hypothesize that the patients heavily calcified bicuspid aortic valve anatomy led to asymmetric deployment of the transcatheter aortic valve replacement (TAVR) prosthesis, traumatizing the right sinus of Valsalva at the distal edge of the TAVR stent and ultimately fistulized to the right ventricle. The patient acutely decompensated with heart failure five days after TAVR and underwent emergent intervention. The aorto‐right ventricular fistula was closed using an 18‐mm septal occluder device with marked clinical recovery. Transcatheter closure is a viable treatment option for acute aorto‐right ventricular fistula.

Progressive Onset of Extracardiac and Myocardial Symptoms: Right Heart Failure and Cor Pulmonale in a Young Man With Debilitating Polyneuropathy and Monoclonal Gammopathy.

Information about a real patient is presented in stages (boldface type) to expert clinicians (Drs Yee and Dudzinski), who respond to the information, sharing reasoning with the reader (regular type). A discussion by the authors follows. A 34-year-old man with a 2-year history of unexplained steroid-refractory polyneuropathy, lower-extremity edema, and monoclonal gammopathy presented to our tertiary care center with 3 days of rapidly progressive dyspnea. The patient’s vital signs were notable for a temperature of 37.0°C, heart rate of 122 bpm, blood pressure of 80/60 mm Hg, respiratory rate of 22 breaths per minute, and oxygen saturation of 94% on 2 L supplemental oxygen. Physical examination revealed a cachectic young man in mild respiratory distress with a jugular venous pressure of 12 cm H 2 O and a positive Kussmaul sign, pulsus paradoxus of 6 mm Hg, regular tachycardic rhythm without murmur or gallop, but a prominent P2 sound with heave at the left sternal border, bilateral fine crackles, and decreased bibasilar breath sounds. Abdominal examination revealed mild hepatomegaly. Peripheral examination was notable for warm and well-perfused lower extremities with 2+ pitting edema extending to the sacrum but without evidence of venous stasis dermopathy, leg tenderness, erythema, warmth, or palpable cord. There was also mild, diffuse skin hyperpigmentation. Dr Dudzinski: On this acute presentation with new dyspnea and hypotension, the onus is on the cardiologist to rapidly evaluate and exclude possible diagnoses such as pulmonary embolism (PE), myocardial infarction, pericardial tamponade, and decompensated heart failure. Jugular venous distention can be consistent with all of these diagnoses, but it importantly excludes other shock phenotypes such as distributive (eg, septic) or hemorrhagic shock. Pitting pedal and sacral edema may also be consistent with elevated central venous pressures; the lack of stasis dermopathy …

Significance of ST-Segment Elevation in Lead aVR—Quiz Case

A 69-YEAR-OLD MAN WITH A HISTORY OF HYpertension, hyperlipidemia, active tobacco smoking (35 pack-years), and atrial flutter status post successful electrical cardioversion self-presented to the emergency department for 1 month of progressively worsening dyspnea on exertion and 2 days of frequent episodes of exertional and nonpleuritic mid-sternal chest pressure. He did not have a known history of coronary artery disease or diabetes mellitus, although there was a paternal history of fatal myocardial infarction at age 54 years. The patient was asymptomatic at the time of presentation and an electrocardiogram (ECG) was obtained (Figure 1). The ECG was remarkable for 1-mm ST-segment elevation in lead aVR, submillimeter STsegment elevation in lead V1, and ST-segment depressions in leads II, III, aVF, and V4 through V6. Questions: Are the noted ECG findings concerning for a critical coronary artery lesion? What is the most appropriate next step in evaluation and management?

A 57-Year-Old Man With Insidious Dyspnea and Nonpleuritic Chest and Back Pain

A 57-year-old man with a history of DVT and pulmonary embolism, transient ischemic attacks, prior 60 pack-year smoking history, and oxygen-dependent COPD presented with insidiously worsening dyspnea associated with new pleuritic chest and back pain.

Transcoronary pacing threshold predicts myocardial scar: Novel first-step towards intraprocedural myocardial functional assessment

Key Points • Transcoronary pacing (TCP) is a novel modality to assess the subtended myocardium during percutaneous coronary intervention (PCI). • In a proof-of-concept trial of six patients, TCP threshold discriminated scar from normal myocardium in the left anterior descending coronary distribution. • Further investigation is needed to determine whether TCP can assess myocardial viability to inform intraprocedural decision making.

Long‐term clinical observations for a biofunctionalized stent: Yet to deliver their theoretical benefits

Endothelial progenitor cells (EPCs) may allow accelerated and functional endothelialization of stents, theoretically reducing late stent complications as well reducing the duration of DAPT. In a pilot study of 193 patients at high risk of target vessel failure (TVF), the Genous EPC capturing stent (ESC) and TAXUS Liberté paclitaxel‐eluting second‐generation stent (PES) were similar at 5‐years. Events rates appear higher for ESC within the first‐year followed by higher rate of complications for PES during years 2–5. A larger randomized multi‐center trials powered for non‐inferiority of ECS to PES is underway.

ECHOCARDIOGRAPHIC ASSESSMENT OF CALCIFIC MITRAL STENOSIS OVERESTIMATES SEVERITY COMPARED TO RHEUMATIC MITRAL STENOSIS

Calcific mitral stenosis (MS) is increasingly prevalent in industrialized nations, however its assessment by echocardiography is poorly characterized. Because diminished left atrial compliance may impact mitral gradients in calcific MS, we sought to compare the accuracy of echocardiography in

Pathology of Endovascular Stents

Contemporary endovascular stents are the product of an iterative design and development process that leverages evolving concepts in vascular biology and engineering. This article reviews how insights into vascular pathophysiology, materials science, and design mechanics drive stent design and explain modes of stent failure. Current knowledge of pathologic processes is providing a more complete picture of the factors mediating stent failure. Further evolution of endovascular stents includes bioresorbable platforms tailored to treat plaques acutely and to then disappear after lesion pacification. Ongoing refinement of stent technology will continue to require insights from pathology to understand adverse events, refine clinical protocols, and drive innovation.