Editor's Note: This is the fourth and last part of our interview series on coronavirus disease 2019 (COVID-19). It has been an interesting view of early responses to the COVID-19 pandemic from cardiology practitioners in the United States and Italy. Part 4 is unique because the first 6 questions and answers were recorded in May, but the last question and answers were recorded in August. Therefore, we have the opportunity to reflect on early responses alongside current thoughts about the pandemic and its overall effect. Thanks to these physicians for their time, insight, and the willingness to extend the interview process. I hope you find this as interesting as I have as we try to understand and manage the challenges of this pandemic.

Question 1: First, what types of cardiac symptoms have you seen, and how frequently have patients demonstrated them?

Giuseppe Biondi-Zoccai, MD: To be frank, where I practice in Rome and in Latina, in Central Italy, we have benefited from the early national lockdown prompted by the emergency in Northern Italy. Accordingly, we have mainly seen classic pneumonia-like COVID-19 cases, occasionally requiring noninvasive ventilation. Cardiovascular mimicry (i.e., COVID-19 presenting as cardiovascular disease) has occurred but in very few cases. Mostly, we have seen indirect effects of the COVID-19 scare, with fewer patients activating the STEMI network early on, and some not activating it at all.

Parag M. Doshi, MBBS, FACC: I have seen dyspnea persisting long after the systemic symptoms have dissipated, also profound body ache with weakness in a patient with heart failure (HF) with preserved ejection fraction HFpEF.

Amir Kaki, MD, FACC: In my experience, with a lot of COVID-19 patients in Detroit, the overwhelming majority have presented with respiratory symptoms. There have been isolated cases that have presented with thrombotic complications of COVID-19 including deep vein thrombosis, pulmonary embolism, left intracardiac thrombosis, and acute limb ischemia.

Michael P. Savage, MD, FACC: The primary presentation has been fever, cough, and respiratory failure (shortness of breath). We have many cases like these but have seen very few patients with suspected COVID-19 myocarditis or pseudo-STEMI, which have been described by others.

Rajiv Tayal, MD, MPH, FACC: I think my perspective is a little different. I covered 2 weeks of STEMI call, the cardiac care unit for a week, and then spent the last several weeks splitting 12-hour shifts with my colleagues to cover COVID-19 units because, for a while, things in Newark were in total disarray. Through that, we have seen extremely broad and at times totally unexpected presentations of COVID-19. At first, there were a lot of acutely ill, previously totally healthy young patients. Most of those now remaining in house are the elderly or chronically ill patients with significant comorbidities. In terms of cardiac presentations, we have seen a handful of the much-tweeted-about "false" STEMIs where patients presented with chest pain, had well-defined ST-segment elevations but, retrospectively, did not have the reciprocal changes that we most commonly expect to see but normal coronaries. But much more commonly than that we saw a lot of patients presenting with "troponinemia" with troponin elevations ranging from borderline high to significantly elevated, which at that point shifted more toward at point of care echocardiogram in the emergency department prior to further decision-making. We had a few with pericardial effusions, others present with syncope, and had 1 that stayed in our cardiac care unit for several days dependent on a temporary pacemaker after progressing into a complete heart block. We also had a fair number of patients also presenting with acute myocarditis and pericarditis-type presentations with elevated troponins, acute reductions in systolic function, and concomitant HF symptoms, most without prior history of HF but with definitive underlying risk factors such as hypertension, diabetes mellitus, etc. Beyond that, there was a relatively high frequency (or seemingly disproportionate number) of patients with acute thromboembolic events, predominately affecting the lower extremities, with several also resulting in moderate to large pulmonary emboli. A few patients were also coagulopathic, which was also challenging to manage. It really at times just seemed to be all over the map.

Question 2: There have been very few recognized heart attacks but a variety of myocardial injuries associated with COVID-19. How have you distinguished STEMIs from COVID-19 myocardial injury?

Biondi-Zoccai: Again, the experience accrued so far in Rome and Latina has been not very dramatic. I am aware of some takotsubo-like COVID-19 cases, but so far at Goretti Hospital, most STEMI cases were due to traditional atherothrombotic pathophysiology. In some patients we recognized COVID-19 as a comorbidity later on, but it remains unclear whether infection was concomitant before the STEMI or actually occurred during hospitalization.

Doshi: It's based on clear classic textbook electrocardiogram defining a vessel. If in doubt, quick bed side echocardiography has been helpful.

Kaki: Yes, I have distinguished between the two and found that patients who have reciprocal changes on the electrocardiogram are more likely to have epicardial thrombotic occlusions of the coronary artery. Furthermore, a point-of-care ultrasound has helped guide decision-making in STEMI patients with COVID-19.

Savage: Most of the STEMIs we have seen during the pandemic were COVID-19 negative. We have not seen pseudo-STEMI with COVID-19. A few COVID-19-positive patients developed STEMI in their terminal stages in the setting of refractory respiratory failure and hypoxia.

Tayal: There was a patient we took to the laboratory with a suspected STEMI who was found to have normal coronaries before shifting to point-of-care echocardiography first and really examining the electrocardiograms for reciprocal changes. Since then, it has been extremely quiet in terms of STEMI activations. We have seen a few late presenters coming in after weeks of symptoms, mostly "Q'ed" out but nothing quite as dramatic as a few cases I saw on Twitter.

Question 3: STEMIs are down for patients without COVID-19 as published. Do you think out-of-hospital deaths have increased, suggesting that people have avoided coming to hospitals with dire consequences?

Biondi-Zoccai: We all believe in Italy that patients have activated the STEMI network less timely, if at all. Accordingly, we have both anecdotal and statistical data highlighting a dramatic increase in all-cause death in Italy. Part of this increase is clearly due to COVID-19, but part is evidently due inadequate management of common and risky conditions such as STEMI.

Doshi: Not even a question. Just got done talking to a friend's father, who developed burning chest pain and weakness. He did not go to hospital for 24 hours, but finally his daughter convinced him to go to the emergency department. Admission electrocardiogram showed inferolateral myocardial infarction and troponin of 200. Another patient this week came as outpatient with Class IV angina starting 2 weeks ago with ST-segment depression in inferolateral leads. He refused to go to emergency department and reluctantly agreed to catheterization the next day. Catheterization showed occluded left main and a dominant right coronary artery feeding poor collaterals to left system. I have also lost 4 patients with chronic coronary artery disease to sudden cardiac death, highly suspicious for emergency department avoidance based on family conversations.

Kaki: Absolutely. It has been my experience in the Metro Detroit area, and I hypothesize this is mostly related to fear of contracting COVID-19 because the majority of Metro Detroit hospitals are at capacity with COVID-19.

Savage: We are afraid this may be true but have no direct evidence of this. We certainly see people resisting coming to the hospital. We had a middle-aged woman come in with presyncope and complete heart block ~3 days after prolonged chest pain with evidence of recent myocardial infarction and totally occluded right coronary artery; she had no further chest pain and no viability and so was treated with medical therapy and a permanent pacemaker.

Tayal: Absolutely I do. I lost one of my oldest patients whom I had been following for years not because of COVID-19 but because of how it delayed his TAVR, which was really, really hard. I was very close to him and his family.

Question 4: Although COVID-19 is a primary respiratory disease, 20% of patients develop severe cardiac symptoms, with hypotension reported frequently. Have you had experience with intra-aortic balloon pump (IABP), ECMO, or percutaneous ventricular assist devices (pVADs) in this setting?

Biondi-Zoccai: We have limited experience with ECMO in some Rome hospitals, and even less frequent cases of IABP or pVADs. Indeed, our current framework is that COVID-19 management was mistakenly too aggressive a few months or weeks ago in Italy, with early intubation and relatively low threshold for ECMO. Current experience and data suggest instead that a more selective (i.e., restrictive) policy for intubation and mechanical support should be sought to avoid causing major iatrogenic complications or other adverse events associated with invasive treatments (e.g., bacterial infection, thrombosis, and bleeding).

Doshi: ECMO has been used by my colleagues in a couple of patients with dismal results. None of my patients, who happen to be old, have been placed on ECMO.

Kaki: We have had successful cases using right-sided pVAD in a patient with acute right ventricle failure secondary to massive pulmonary embolism and intracardiac thrombus.

Savage: The biggest problem is oxygenation, so we have had several patients on ECMO.

Tayal: Only a small minority of patients were treated with IABP and fewer with ECMO. I am not certain if any of my colleagues used pVADs. To the best of my knowledge, the outcomes were not good across the spectrum.

Question 5: You must have a huge backlog of patients whose elective procedures have been postponed. Have you seen adverse events in the patients "in-waiting?" Do you plan to triage patients by order of restarting testing and procedures? If so, how?

Biondi-Zoccai: This depends a lot on the type of practice before the COVID-19 emergency. Our backlog of elective cases was not huge, and we still can perform a few carefully selected elective cases provided that the clinical indication is clear. Evidently, many of us think that the whole approach to managing cardiovascular disease will have to be revised, given the need to invest in COVID-19 treatment and rehabilitation and the more or less explicit resource triage discouraging expensive treatments without life-saving implications in the elderly (e.g., PCI for chronic total occlusions).

Doshi: I believe that I have avoided the adverse events with being highly accurate and detailed in history taking and recording the high-risk symptoms. Our hospital allows outpatient catheterization in high-risk situations. Almost all of my outpatient coronary angiography patients have had critical disease in major epicardial arteries requiring stents or coronary artery bypass grafting as well. Being in outpatient independent group practice, we have continued outpatient testing and office-based vascular laboratory procedures as well. Fanatical precautions have been instituted with huge numbers of wipes used, personal protective equipment (PPE) for all the staff, and mandatory masks for the patients. Every patient is screened by phone call and again at the front desk. Relatives are not allowed in the office. The waiting room has patients 10-15 feet apart, and they are usually whisked away to the room. The hospital is going to allow elective procedures on May 11th for intermediate-risk patients. There are a maximum 10 patients per day, and all patients will have COVID-19 polymerase chain reaction test within 72 hours prior to the procedure.

Kaki: Yes, I have seen patients with unstable symptoms that degenerate into cardiogenic shock. Furthermore, we have seen patients with acute coronary syndrome who would normally get catheterizations being treated medically and suffer worse outcomes. We are planning on starting elective procedures based on patient symptoms and severity to give priority to sicker, more symptomatic patients.

Tayal: It's almost been trial by fire, if you will. You can talk to patients during telehealth visits, call them on the phone, give them your cell phone (I give all my patients my cell) and tell them to call you if they have cardiac symptoms, but the reality is that, even now as things seem to be leveling off, a lot of them are still riddled with fear from what they see on the news or social media and are still reluctant to come in. The other complicating factor here is that not everything we do is black and white in terms of elective versus urgent because elective can become emergent all too quickly. I've got a patient with distal left main and triple vessel disease that was a surgical turndown who has been waiting for weeks, and then also several patent foramen ovale closures that almost fall on opposite ends of the spectrum, with a lot of patients with valvular heart disease in the middle somewhere.

At the moment, we have been doing emergent and urgent cases only but plan on resuming a limited number of the more pressing outpatient elective cases next week along with outpatient cardiac testing services like echocardiography, stress, computed tomography initially at about 25% capacity then ramping up every week thereafter.

Question 6: What are your overall insights? What observations would you like to make? What else should we know as we re-expand practice?¹

Biondi-Zoccai: Our experience in Latina has been, to date, benign. It is likely that other colleagues were not adequately forewarned and thus put themselves and their patients at risk. Conversely, we have been able so far to treat our cardiovascular patients and devote additional resources to COVID-19 care while avoiding being infected. From a scholarly perspective, it is also true that COVID-19 has some important implications: a renewed collaborative approach at research, a focus on what really works, a push toward truly translational research, and the recognition that telemedicine is not just a gimmick but may actually improve patient outcomes.

Doshi: I believe the following:

1. Politics and partisanship replaced hard-nosed science in the epidemic. This is true for both republicans and democrats.
2. We failed to institute vigorous testing and contact tracing early on, but we also, to some extent, instituted total shut down of the country, which is clearly not feasible for a very long period and certainly cannot be carried out until the vaccine is ready.
3. I have never been as scared as I am now in terms of getting COVID-19 and bringing it home to my wife and family. It is simply unacceptable that a country that spends billions and billions of dollars in health care could not support its health care industry with the most basic needs: PPE.

Kaki: If you are in a hard-hit city or environment, I strongly recommend assuming that all patients coming in through the emergency department are possible COVID-19 transmitters and use proper PPE to protect yourself and staff.

Savage: COVID-19 testing is not perfect, so our mantra is to assume that every patient coming to the catheterization laboratory has COVID-19 and to take appropriate PPE precautions. One controversial issue is how aggressive to be in screening people for COVID-19 who are coming in for outpatient catheterization pre-procedure. I put out a Twitter poll on this issue on April 27. Of the 400 respondents, 52% test routinely, 32% test only if patient has had symptoms, fever, or contact, and 16% usually don't test. So, about half test routinely and about half don't.

Tayal: It's hard to say, but this is certainly something that will stay with all of us, forever, in one way or another. To be honest, my initial reaction before the peak hit New York was this has to partly be media hype, and maybe I should consider switching to Fox News. But within minutes of my first day on the floors and in the unit, I was speechless (or maybe just breathless from the masks I was wearing) and totally convinced otherwise. It really felt like I was in a bad movie that started and ended in an alternate reality. We had a number of our own faculty members and fellows contract COVID-19, all with varying presentations and degrees of symptoms ranging from nearly asymptomatic to having two of them ultimately lose their battle with the virus. I personally think a lot of staff members were infected well before the pandemic officially broke out into mainstream thought because most presented with HF/cardiac symptoms. I think initially some of us were not well prepared in terms of personal knowledge of how best to protect ourselves even when PPE was available, something we all should have taken and learned from our international colleagues where it hit before the United States. Although initially rationed, I think our administrators, teams, and communities pulled together to make sure everyone was as well equipped as could be hoped for, although what we wore and what the Chinese practitioners were wearing on TV seemed to be very different (meaning ours were much less elaborate).

Personally, when you're someone with young kids at home, you initially fear for them and your family more than yourself. But as you gain experience and exposure, you gain confidence, comfortability, and trust in your team in knowing that you will get through this together, one way or another. I had initially self-quarantined. Afterwards, I think one of the unintended positives for me personally that came from all of this, in moving to shift-type work and with the cancellation of elective procedures, conferences, proctorships, etc., is that I have been home and able to not only spend more time with my kids than I ever have before, but also be present when I am and not on my phone answering a page or following up on an email. I was also able to finish up work on several manuscripts after running into a pretty severe case of writer's block. Not to make light of the situation by any means, but I think it's important to find a means to acknowledge any positives amidst such significant tragedy and loss that we will all bear for a long time but undoubtedly emerge stronger from.

Question 7: Finally, given the increasing knowledge about the complications and complexity of COVID-19 infections such as the intense inflammatory response, thrombosis and the deferred or absent medical care of "usual" cardiac disease, please comment on specific new or continued approaches that you are using as the resurgence occurs.

Biondi-Zoccai: The last few months in Italy have been perplexing. We expected a deluge of new cases in May and June, but despite some increases, COVID-19 seems still to be manageable. We will see in September and October, after schools and universities open again. Focusing more on the personal side, I must be frank. I have found the COVID-19 emergency paradoxically refreshing. We have all been forced to refocus on what is really important—family, friends, work—recognizing that many things we considered important were simply paraphernalia of the few important ones.

Doshi: I have come to believe that exposure to the virus is unavoidable, but the severity of infection may depend on the viral load being introduced in the body. Specifically, for me and my team, it is critically important to enforce the facial mask and screening for patients and employees. I refuse to enter the patient room or catheterization laboratory unless the mask is covering the nose. I wear my N95 all the time.

With the above in mind, I also believe that end may not be in sight and that the virus is likely to linger on. It is not appropriate to delay care or even elective procedures anymore. In cardiology, even an elective procedure or test advised is, by definition, designed to reduce major adverse cardiac events. I had a 33-year-old female patient who was brought in with sustained ventricular fibrillation and died after 24 hours with anterior STEMI despite full support and left anterior descending artery stent. She had pain for 3 days but did not go to the emergency department due to the fear of COVID-19. I can go on and on with similar examples of disasters due to the care deferred in the COVID-19 era.

I am perpetually carrying the foreboding and anxiety of what is next. Our professional societies and, more importantly, our government have failed to really understand or help with this in a comprehensive fashion. This is likely present in all the health care workers. Is this also going to affect the number and quality of new medical school applicants?

Kaki: As we learned more about this pandemic and the cardiopulmonary implications of the infection, we evolve in the way we treat these patients. For example, we are treating all of our STEMIs with primary PCI and taking the necessary precautions to mitigate transmission risks. We are using ECMO early in the course of ventilator-dependent respiratory failure. We are actively doing elective cases and implementing same-day discharge for PCI. In patients for whom surgery and high-risk PCI are both amenable, we have performed PCI so that we can decrease patients' hospital days. These are some examples of how we have successfully adjusted our practice to mitigate and reduce exposure for a vulnerable population. We don't know when this pandemic will end, and, as such, we are continually learning and adapting to best serve our patients.

Savage: Reflection on how we have coped during the COVID-19 pandemic evokes remembrance of the Kubler-Ross stages of dying.² The initial reaction of course was denial (a stage some of our leadership in Washington appear to remain stuck in). Then came anger, bargaining, and depression. In the case of the pandemic, these stages often seemed to be happening all at the same time. A classic expression of this is the hashtag #WearADamnMask, where anger and bargaining are directed at individuals still in a state of denial and unwilling to comply with the social interventions necessary to control the pandemic.³ I suspect that most of us, physicians and our allied health colleagues in the trenches, have progressed to the stage of acceptance: that this is the "new normal" for the foreseeable future, a brave new world of caring for patients masked up, gloved up, with minimal laying of hands (certainly no handshakes). Rather than in-person medical meetings where knowledge and new ideas are exchanged in a social atmosphere, we have a brave new world of sterile virtual conferences and Zoom. In the view of many, the future appears murky and foreboding. As for me, I remain an unwavering optimist. I believe that our collective perseverance, ingenuity, and courage will ultimately triumph over this pestilence.

Tayal: That truly is a great question. And unfortunately, still somewhat of a hard one to answer as we continue to shoot at a moving target. Despite all that we feel we may have learned over the course of the past 5-6 months and evidence that we may have gotten better at treating the virus, we still have a long way to go.

Of the lessons learned, I think some of the key take homes from our experience are these:

• Early identification of the inflammatory response warrants pre-emptive anticoagulation and continued surveillance.
• Standardized but limited point-of-care echocardiograms were helpful in early triage and identification of patients presenting with cardiovascular symptomatology such as abnormal electrocardiograms that at times mimicked acute myocardial infarctions or in patients with elevated cardiac biomarkers.
• Deferment of invasive treatment, whether that be PCI for an acute coronary syndrome, unstable angina, or particularly for hemodynamically unstable patients due to COVID-19 or patient-under-investigation status clearly portended worse outcomes. Although those patients who were found to be positive did worse more often than those who were not, they still did much better than those who were not intervened on or supported as needed.

We initially had a number of faculty, fellows, and catheterization laboratory nursing staff who doubled as cardiac care unit nurses initially while elective procedures were postponed contract the virus; however, despite everyone's fears, after we began screening and treating every patient as a presumed positive during the peak of the pandemic, our staff remained safe in the laboratory despite prolonged and close contact with patients. A slow, methodical roll out and resumption of elective procedures seemed to work well. Overall, the thrombus burden seen during acute coronary syndromes seemed to be much higher, but the number of patients presenting with true acute coronary syndrome or, in particular, STEMIs dramatically declined.

We actually lost a few patients at home who postponed "elective" procedures such as a staged PCI and a patient waiting to undergo TAVR, which was extremely heart breaking and unfortunate. As we all know, a lot of what we do falls on a grey line between the black and white of things considered elective or emergent. From that, we found it extremely important to reach out to contact and speak to patients through a plethora of telehealth platforms (made available seemingly overnight, many of which were free) or even by phone to make them aware of the services offered, screen them for progressive symptoms, and reassure them when appropriate.

During the peak of the pandemic, we were stretched beyond capacity and had converted several pre-operative holding areas and operating rooms into COVID-19 units. Once things settled down, we worked hard to separate COVID-19 +/- patients by PODS or units within the hospital. All patients who were brought in for elective procedures had to have nasal swabs and self-quarantine for 48 hours prior to the procedures and came to the hospital without visitors. We have also implemented same-day discharge policies for several procedures including WATCHMAN, MitraClip, and TAVR. I even did a single-access, five-vessel Impella-supported PCI on a gentleman with severe pulmonary fibrosis whom we sent home the same day after his "percutaneous coronary artery bypass grafting." He continues to do very well, and his case may very well prove to be a glimpse into the new normal of complex cardiovascular care during these unprecedented times and beyond.

References

1. Wood DA, Mahmud E, Thourani VH, et al. Safe Reintroduction of Cardiovascular Services During the COVID-19 Pandemic: From the North American Society Leadership. J Am Coll Cardiol 2020;75:3177-83.
2. Kübler-Ross E. On Death and Dying. New York: Collier Books/Macmillan Co.; 1969.
3. Savage MP, Fischman DL, Mamas MA. Social intervention by the numbers: Evidence behind the specific public health guidelines in the COVID-19 pandemic. Popul Health Manag 2020; in press.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Cardiovascular Care Team, COVID-19 Hub, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Stable Ischemic Heart Disease, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Cardiac Surgery and Heart Failure, Cardiac Surgery and SIHD, Acute Heart Failure, Mechanical Circulatory Support, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging, Chronic Angina

Keywords: Coronary Angiography, COVID-19, Coronavirus, Coronavirus Infections, severe acute respiratory syndrome coronavirus 2, Pandemics, Acute Coronary Syndrome, Cardiovascular Diseases, Contact Tracing, Coronary Vessels, Depression, Coronary Artery Disease, Extracorporeal Membrane Oxygenation, Electronic Mail, Health Care Sector, Heart Ventricles, Heart-Assist Devices, Heart Failure, Myocarditis, New York, Outpatients, Noninvasive Ventilation, Patients' Rooms, Patient Discharge, Percutaneous Coronary Intervention, Personal Protective Equipment, Risk Factors, Schools, Medical, Point-of-Care Systems, Shock, Cardiogenic, Social Media, ST Elevation Myocardial Infarction, Transcatheter Aortic Valve Replacement, Triage, Translational Medical Research, Universities, Troponin, Ursidae, Vulnerable Populations

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