Paolo Angelini

This paper presents a fully integrated current sensor based on an integrated shunt resistor supporting a 25V common mode input while operating at 1.2V supply voltage. It can detect a current between ±4A. It uses a novel time based architecture to increase sensor accuracy over temperature, mechanical stress and lifetime. This architecture is based on the integration of a replica of the current to sense using a switched capacitor integrator with reset working with a very accurate clock signal. With this technique sensor’s gain is not sensitive to temperature variation, mechanical stress or lifetime variation of the shunt resistor. On the other hands, its accuracy is limited only by a capacitor and the clock period variation. Their variation are much smaller than the ones of a resistor. The overall gain of this architecture achieves a precision of 1/1000 over temperature variation.

An 86-year-old woman being treated for metastatic breast cancer developed severe chest pain at rest during a follow-up visit at a hospital's outpatient oncology clinic. An electrocardiogram showed severe ST-segment elevation. The patient was given sublingual nitroglycerin and was transferred to the emergency department. Diagnostic coronary angiography revealed moderate coronary artery disease with calcific stenoses and transient spastic occlusion of the left anterior descending coronary artery. For this patient, sublingual nitroglycerin aborted the spastic event and apparent transient takotsubo cardiomyopathy. Chemotherapy can potentially cause endothelial dysfunction and increased coronary spasticity, which could result in takotsubo cardiomyopathy.

In this issue of the Journal, Yalamanchi et al1 describe the case of a young male patient with COVID-19 who appeared to recover quickly but soon developed acute congestive heart failure with a left ventricular ejection fraction of 20% and a global pattern of critical hypokinesia. This case is clearly important, but the presentation and explanation of the possible pathophysiologic mechanisms are confusing.Apparently, the patient recovered relatively quickly and had a near-normal left ventricular ejection fraction in 1 month. The most likely diagnosis in such a case—transient takotsubo cardiomyopathy (TTC)—should have been quickly ruled out. The reported testing seemed to have ruled out myocardial scarring (coronary embolism and myocarditis) but not TTC. The early disappearance of severe cardiomyopathy is pathognomonic of TTC by itself.At this time, in similar cases (which are generally rare but encountered fairly frequently at specialized centers), acetylcholine testing is needed urgently to identify the specific cause of patient's endothelial dysfunction.2 Preliminary results suggest that acetylcholine testing for this indication is feasible, safe, and specific for endothelial dysfunction (when the test result is positive). Thus, acetylcholine testing seems to be a good option in any case of either acute ischemic syndrome with cardiomyopathy or myocardial infarction with nonobstructive coronary arteries or of acute myocardial infarction with a “normal coronary tree.”One of the most convincing current theories regarding TCC claims that its root cause is endothelial dysfunction (in cases of COVID-19, endothelial dysfunction resulting from endotheliitis caused either by direct viral infection or inflammatory disease).3,4 The biological state characterized by endothelial dysfunction is not yet clearly understood, but it seems a logical reason to induce coronary spasm with acetylcholine, especially in a patient with stress, respiratory distress, anxiety, and fever caused by COVID-19. In similar cases, endothelial dysfunction manifests as an acute event (typically with chest pain and dyspnea) and leads quickly to left ventricular dysfunction. With advanced testing, the authors ruled out both myocarditis and acute myocardial infarction.1 An early acetylcholine test for endothelial dysfunction would have been a simple and safe alternative, but it requires specialized techniques that may not be available in all catheterization laboratories. Such testing facilitates reliable documentation of a reproducible mechanism (coronary artery spasm) and response to nitroglycerine.In addition, this unfortunate patient was in a severely hypercoagulable state, with multiple systemic embolisms. Most likely, the emboli originated in the left ventricle, as indicated by dimerized plasmin fragment D elevation and pointing to TTC. Recent evidence suggests that TTC occurrence has been 4 to 5 times more frequent during than before the COVID-19 pandemic.4Acetylcholine testing is indicated for establishing a diagnosis and selecting treatments for individual patients. It also creates opportunities to collect useful data from large TTC populations.

Typical emergency hospital care during the COVID-19 pandemic has centered on pulmonary-focused services. Nonetheless, patients with COVID-19 frequently develop complications associated with the dysfunction of other organs, which may greatly affect prognosis. Preliminary evidence suggests that cardiovascular involvement is relatively frequent in COVID-19 and that it correlates with significant worsening of clinical status and mortality in infected patients. In this article, we summarize current knowledge on the cardiovascular effects of COVID-19. In particular, we focus on the association between COVID-19 and transient takotsubo cardiomyopathy (TTC)—two conditions that preliminarily seem epidemiologically associated—and we highlight cardiovascular changes that may help guide future investigations toward full discovery of this new, complex disease entity. We hypothesize that coronary endothelial dysfunction, along with septic state, inflammatory storm, hypercoagulability, endothelial necrosis, and small-vessel clotting, may represent a fundamental hidden link between COVID-19 and TTC. Furthermore, given the likelihood that new genetic mutations of coronaviruses or other organisms will cause similar pandemics and endemics in the future, we must be better prepared so that a substantial complication such as TTC can be more accurately recognized, its pathophysiology better understood, and its treatment made more justifiable, timely, and effective.

Retrocardiac course of an ectopic right coronary artery is newly described. The alternative (usual) course of an anomalous right coronary from the left sinus of Valsalva is pre-aortic and intramural, with stenosis. In the present exceptional case, there was no stenosis.