key: cord-0812045-bzj59q3k
authors: Tovia-Brodie, Oholi; Acha, Moshe Rav; Belhassen, Bernard; Gasperetti, Alessio; Schiavone, Marco; Forleo, Giovanni Battista; Guevara-Valdivia, Milton E.; Ruiz, David Valdeolivar; Lellouche, Nicolas; Hamon, David; Castagno, Davide; Bellettini, Matteo; De Ferrari, Gaetano M.; Laredo, Mikael; Carvès, Jean-Baptiste; Ignatiuk, Barbara; Pasquetto, Giampaolo; De Filippo, Paolo; Malanchini, Giovanni; Pavri, Behzad B.; Raphael, Craig; Rivetti, Luigi; Mantovan, Roberto; Chinitz, Jason; Harding, Melissa; Boriani, Giuseppe; Casali, Edoardo; Wan, Elaine Y.; Biviano, Angelo; Macias, Carlos; Havranek, Stepan; Lazzerini, Pietro Enea; Canu, Antonio M.; Zardini, Marco; Conte, Giulio; Cano, Óscar; Casella, Michela; Rudic, Boris; Omelchenko, Alexander; Mathuria, Nilesh; Upadhyay, Gaurav A.; Danon, Asaf; Schwartz, Arie Lorin; Maury, Philippe; Nakahara, Shiro; Goldenberg, Gustavo; Schaerli, Nicolas; Bereza, Sergiy; Auricchio, Angelo; Glikson, Michael; Michowitz, Yoav
title: Implantation of Cardiac Electronic Devices in Active COVID-19 Patients. Results from an International Survey
date: 2021-10-26
journal: Heart Rhythm
DOI: 10.1016/j.hrthm.2021.10.020
sha: c9fd5764055c2ad472a3109d4f63c081a52cc3d3
doc_id: 812045
cord_uid: bzj59q3k

BACKGROUND: Cardiac implantable electronic device (CIED) implantation rates, as well as the clinical and procedural characteristics and outcomes in patients with known active COVID-19 are unknown. OBJECTIVE: To gather information regarding CIED procedures during active COVID-19, performed with personal protective equipment, based on an international survey. METHODS: Fifty-three centers from 13 countries across 4 continents provided information on 166 patients with known active COVID-19 who underwent a CIED procedure. RESULTS: CIED procedure rate in 133,655 hospitalized COVID-19 patients ranged from 0 to 16.2 per 1000 patients (p<0.001). Most devices were implanted due to high degree / complete AV block (112, 67.5%) or sick sinus syndrome (31, 18.7%). Of the166 patients surveyed, the 30-day complication rate was 13.9% and the 180-day mortality rate was 9.6%. One patient had a lethal outcome as a direct result of the procedure. Differences in patient and procedural characteristics and outcomes were found between Europe and North America. An older population (76.6 vs. 66 years, p<0.001) with a non-significant higher complication rate (16.5% vs. 7.7%, p=0.2) were observed in Europe, while a higher rate of critically ill patients (3.3% vs. 33.3%, p<0.001) and mortality (5% vs. 26.9%, p=0.002) were observed in North America. CONCLUSION: CIED procedure rates during known active COVID-19 disease varied greatly from 0 to 16.2 per 1000 hospitalized COVID-19 patients worldwide. Patients with active COVID-19 infection who underwent CIED implantation had high complication and mortality rates. Operators should take into consideration these risks prior to proceeding with CIED implantation in active COVID-19 patients.

Hebrew University, Jerusalem, Israel. Coronavirus disease 2019 is caused by the novel severe acute respiratory syndrome 133 coronavirus 2 (SARS-CoV-2). Since late December 2019 the world has faced a pandemic caused 134 by COVID -19, with over 160 million people affected leading to over 3 million deaths 1 . The 135 main clinical manifestation of COVID-19 is respiratory disease, but cardiac manifestations have 136 been reported in a substantial number of hospitalized patients, including cardiac arrhythmias. 2 In 137 a recent worldwide case series 18.3% of admitted COVID-19 patients suffered a cardiac 138 arrhythmia. 3 About 70% of patients who developed an arrhythmia, presented atrial 139 tachyarrhythmias, with bradyarrhythmia seen in approximately 20% of patients. Atrioventricular 140 block (AVB) was noted in 1.57% of COVID-19 admitted patients, and sinus pauses >3 sec. in 141 only 0.22%. 3 Among COVID-19 patients with telemetric monitoring 3.5% had AVB. 4 Several 142 studies have reported a substantial decrease in overall cardiac implantable electronic device 143 (CIED) implantation rates during the pandemic, none of which reported the procedure rate in 144 patients with active COVID-19 disease. [5] [6] [7] [8] [9] [10] There are only a few case reports and small case 145 series in the literature of patients with COVID-19 who were implanted with a CIED while 146 having active disease, and none reported procedural complications. 11-21 Active COVID-19 has 147 implications for treating physicians and staff, and impacts CIED planning. The implanting 148 physician and supporting staff need to wear personal protective equipment (PPE) during the 149 procedure with possible impairment in their ability to perform the procedure. Optimal 150 indications, timing and periprocedural management are unclear. The Heart Rhythm Society, 151

American College of Cardiology, and the American Heart Association released a joint statement 152 with recommendations regarding the management of electrophysiologic procedures which are 153 primarily based mainly on expert opinion, acknowledging there are limited published data 154 9 currently available on arrhythmia management in It is unknown whether 155 early implantation during active COVID-19 disease is beneficial or associated with a higher 156 complication or mortality rate, and whether different device types may carry a different risk of 157 complications. As many centers implanted only few devices and in order to gather clinically 158 relevant information, we conducted an international survey. We received responses from 53 159 centers in 13 countries across 4 continents. We sought to assess the rate of device implantation, 160 the patient and procedural characteristics and the outcomes of all types of CIED implantations 161 and replacements during active 163

The Shaare Zedek Medical Center Institutional Review Board committee approved the study. All 165 centers complied by local IRB registry protocols. Share Zedek Medical Center served as the 166 coordinating center. 167

A Medline search using the terms "COVID-19 or SARS-CoV-2 and device implantation or 169 atrioventricular block or bradyarrhythmias" was performed to select worldwide centers with 170 experience in the diagnosis and management of active COVID-19 and device implantations. In 171 addition, multiple world-known electrophysiologists were contacted and offered to participate in 172 an international multicenter survey on device implantations in active COVID-19 patients. 173

Patients were eligible if they fulfilled both conditions: a) they were diagnosed with active 175 COVID-19 illness (confirmed by nasopharyngeal polymerase chain reaction testing) 176

immediately prior to the procedure; b) the operator and supporting staff needed to use PPE, in 177 J o u r n a l P r e -p r o o f 10 compliance with hospital recommendations. Patients were excluded from the study in the 178 following instances: 1) they underwent implantation of a temporary transvenous pacing (TVP) or 179 of an implantable loop recorder; 2) CIED was implanted after recovery from COVID-19 without 180 use of PPE; 3) CIED was implanted in active but unrecognized COVID-19 patients without the 181 use of PPE. 182

Disease severity was classified according to the following degrees: 

Fifty-three centers from 44 cities, belonging to 13 countries in 4 continents participated in the 216 study. The 53 participating centers composed of 33 centers which implanted CIEDs in active 217 COVID-19 patients and 20 which replied no device implantation that met the inclusion criteria 218 occurred in their center, of whom 14 provided the number of hospitalized COVID-19 patients 219 since the beginning of the pandemic and until the data collection, and in 6 this data was 220 unavailable (3 from Israel, 2 from Canada and 1 from Hong Kong). 221

Forty-four centers provided the number of hospitalized COVID-19 patients at their center since 223 the beginning of the pandemic till data collection (In 3 centers which provided data on CIED 224 implantations, the total number of hospitalized COVID-19 patients was unavailable, 2 from 225 Israel, 1 from USA, with 1, 2 and 5 procedures, respectively). CIED procedure rate in 133,655 226 hospitalized known COVID-19 patients ranged from 0 to 16.2, with crude rate of 1.17 per 1000 227 hospitalized COVID-19 patients. The rate of CIED procedures per 1000 hospitalized COVID-19 228 patients per country and continent is presented in Figure 1 . The procedural rate varied 229 significantly between the different countries and continents. The average implantation rate was 230 higher in European compared to American centers [1.61 and 0.4 respectively, p<0.001]. 231

The study population included 166 patients (61.4% males), mean age 74.6+12 years, who 233 underwent a CIED implantation (n=159) or replacement (n=7) during active COVID-19 illness, 234 during which the operating physician and staff used PPE. The clinical and procedural 235 characteristics, the complications and mortality of all patients are presented in Table 1 

The majority of devices were implanted due to high degree or complete AV block (n=112, 243 67.5%), followed by sick sinus syndrome (SSS) (n=31, 18.7%). A smaller proportion (n=7, 244 4.2%) were implanted for secondary prevention of ventricular arrhythmias, cardiac 245 J o u r n a l P r e -p r o o f 13 resynchronization therapy (CRT) (n= 5, 3%) while device replacements were performed in 7 246 (4.2%) patients. Other indications were 1 primary prevention ICD, 1 syncope with left bundle 247 branch block, 1 RV lead revision due to lead malfunction (noise) with inappropriate shock, and 1 248 pacemaker-dependent patient who underwent CRTD extraction due to infective endocarditis and 249 was later reimplanted with a single chamber pacemaker. Persistent and transient AV block were 250 seen in 91 (54.8%) and 23 (13.9%) patients; respectively, persistent and transient SSS were seen 251 in 17 (10.2%) and 14 (8.4%) patients; respectively, and ventricular arrhythmia was seen in 7 252 

Three types of PPE were used during the procedures and varied between countries. A full 262 bodysuit including N95 mask, face shield, full body protective suit, sterile gloves and sterile 263 coat, was used in 103 (62%) cases. N95 and face shield only in addition to sterile gloves and coat 264 was used in 56 (33.7%) cases, and N95 only in addition to sterile gloves and coat was used in 7 265 In centers with 80-100% use of full body suit 12/19 (63.2%) of the operators reported feeling 271 impairment in their ability due to protective equipment as compared to 4/14 (28.6%) in centers 272 with <50% (0-40%) use of full body suit, p<0.001). Operators reported the subjective feeling of 273 being hot, sweaty, stressed and having impaired eyesight due to fog accumulation on the face 274 shield and eyeglasses. Anti-fog technology was used in only 6 (3.6%) of cases and included 275 antifog spray and 1 case of ventilator connected to the bodysuit providing airflow inside the 276 bodysuit for prevention of heat, sweat and fog formation. 277

Complications occurred in 23 (13.9%) of the patients, all occurring early within 30 days from the 279 procedure. Supplementary Table 2 details all patients' complications and their clinical and 280 procedural characteristics. One patient who underwent Micra AV implantation (vascular 281 ultrasound was not used for vascular access and a Perclose was used for femoral vein closure), 282 was transferred to another hospital to continue COVID-19 care, where she suffered a 283 hemorrhagic shock due to vascular bleeding and retroperitoneal hematoma (possibly due to 284

Perclose dislodgement) leading to death. Two patients experienced more than 1 complication. 285

One patient suffered from early right ventricular lead dislodgement requiring repositioning, 286 cardiac tamponade after repositioning requiring urgent percutaneous drainage, and at 1-month, 287 atrial lead dislodgement requiring repositioning. Another patient suffered from a significant 288 pocket hematoma and mild pocket infection treated conservatively with antibiotic therapy. 289

On univariate analysis, CRP levels were significantly higher in patients with a complication 290 One operator reported contracting COVID-19 as a result of performing a pacemaker implantation 296 procedure in an active COVID-19 patient. The PPE that was used during the procedure was N95 297 mask and a face shield, without a full body protective suit, as per protocol in that center. 298

The operator consequently developed severe COVID -19 requiring intensive care, but later fully 299 recovered. 300

Sixteen (9.6%) patients of the entire cohort expired ( Table 1) . Death within 30 days and between 302 31-180 days from the procedure occoured in 10 (6%) and 6 (3.6%) patients, respectively. One 303 patient expired as a direct result of a procedural complication (due to hemorrhagic shock as 304 mentioned above), while all other early deaths were attributed to COVID-19 complications 305 unrelated to the procedure. Mortality increased gradually with COVID-19 severity and was 306 4.1%, 6.8%, 14.3% and 38.9% in mild, moderate, severe and critical disease severity, 307 respectively (p<0.001). CRP levels were significantly higher in patients who expired (38.9 308 mg/dL [22.59-183] vs.7.7 mg/dL [3-24.9], p=0.002). Documented pause duration was 309 significantly longer in patients who expired vs. patients who were alive (17 seconds [10-36] vs. 310 5.1 seconds [3.9-6.5], p=0.005). Mortality increased with the use of anesthesia delivered by an 311 anesthesiologist: it was 7.2%, 4.8%, 12.5% and 40% in patients receiving local anesthesia only, 312 in those sedated without anesthesiologist, in those sedated by an anesthesiologist and those 313 receiving general anesthesia, respectively (p=0.007). Mortality was lower during procedures 314 without the presence of an anesthesiologist (6.8% vs. 20.6%, p=0.015). Increased mortality was 315 observed in patients who were implanted with single chamber pacemaker and Micra (either VVI 316 or AV Micra), p<0.001. Patients who expired had significantly increased pre-existing diabetes 317 mellitus (56.3% vs 30%; p=0.03). 318 319

At 1-month FU, abnormal lead parameters (high thresholds) were found in 4 (2.4%) patients, and 321 a pocket infection and pocket hematoma in 1 patient each. Six (3.6%) patients were lost to FU 322 and in 10 (6%) patients less then 30 days passed from the procedure to data collection. At 3-323 month FU, 3 (1.8%) patients remained with abnormal parameters, 22 (13.3%) were lost to FU, 324 and in 44 (26.7%) less then 3 months passed from the procedure to data collection. 325

Multiple differences were found in baseline patients' and procedural characteristics between the 327 different continents. The clinical and procedural characteristics of all the patients according to 328 continent are presented in Supplementary Table 3 This study reports the global rates of CIED implantation or replacements in hospitalized patients 368 with known active COVID-19 disease. We present the largest international cohort of patients 369 who underwent a CIED implantation or replacement during active COVID-19 disease for which 370 the operator and staff had to use PPE. In accordance with the published joint statement 371 recommendations 22 the vast majority of implantations were due to urgent or emergent 372

The primary findings from the present survey include: 374

(1) The complication rate within 30 days for CIED during active COVID-19 was higher than 375 traditional devices, at 13.9%, with more complications noted in Europe or in perceived 376 sicker patients in which an anesthesiologist was used. 377

(2) Mortality rate was also substantially higher than that typically found during CIED 378 implant, of 9.6% at 6 months with higher mortality noted in North America than Europe. 379

(3) Use of PPE varied across region, although use of N95 was present across regions. At 380 least one case of patient to provider transmission of COVID-19 was noted. 381 382

Several large studies have been conducted throughout the world during the last 2 decades for 384 assessing the complication rates following implantation of CIEDs. The MOST trial with a patient 385 population of sinus node dysfunction who underwent dual-chamber pacemaker implantation, 386 reported a complication rate after pacemaker implantation of 4.8% at 30 days and 5.5% at 90 387 days. 23 The FOLLOWPACE study included patients who received a first pacemaker for a 388 conventional reason for chronic pacing, reported a 12.4% complication rate within 60 days. The 389 use of anticoagulant drugs was an independent predictor for complications within 2 months. 24 390

In 2 recent multicenter Australian studies involving 81000 and 32000 patients undergoing a new 391 implantation of a mixed device type, an in-hospital and 90-day complication rate of 3.3% and 392 8.2%; and 8% and 9.6% in private and public hospitals was found, respectively. 25, 26 In addition, 393

in-hospital and 30-day mortality was low (0.46% and 0.7%, respectively). Finally, in patients 394 who needed a reoperation, 30-day mortality increased to 2.76%. 25 395 A large US cohort of 92000 patients undergoing CRT implantation found a 6.1% in-hospital 396 complication rate and 0.76% mortality. Complications increased with older age, increase in 397 comorbidities and non-elective procedures. 27 The Micra investigational device exemption (IDE) 398 prospective study found device complications occurred in 3.4% of patient 28 , while real world 399 data reported an even lower rate of 1.51%. 29 400

We found a high complication rate of 13.9% at 30 days, and a mortality rate of 9.6% at 6 402 months, 6% within 30 days and 3.6% more within 31-180 days of the procedure, much higher 403 than any previous reported large study on CIED implantation or replacements out the setting of 404 COVID-19 disease. [23] [24] [25] [26] [27] [28] [29] The higher complication rate seen in our cohort was likely related to the 405 acute COVID-19 illness, the existence of high comorbidities rate and the fact that elective 406 J o u r n a l P r e -p r o o f 20 procedures on less sick patients may have been deferred. In addition, the use of PPE, reported by 407 many operators to impair their ability to perform the procedure, could have contributed to the 408 high complication rate, even though the difference between PPE types and complication rate did 409 not reach statistical significance. Other unique factors that can explain the high complication rate 410 observed in our cohort are procedures done during an infectious disease with elevated CRP 411 levels, psychological stress on the operator due to personal exposure and risk of contracting 412 COVID-19. "Rushing through" the procedure in attempt to shorten procedural time and 413 minimize self-risk, as well as fog formation on eyeglasses and face shield impairing operator's 414 vision might also affected operator performance. Finally, increased patients' age in addition to 415 higher rate of anticoagulation and steroid therapy use, and higher rate of full bodysuit use, may 416 explain higher complication rate seen in Europe. 417

Higher mortality was seen in North America compared with Europe. A higher rate of severely 419 and critically ill patients were implanted in the US. This is in accordance with other US studies. hospital mortality on the third postoperative day secondary to hypoxic respiratory failure 426 triggered by The use of leadless pacemakers was suggested to reduce operator and 427 staff exposure, and to reduce complications and hospitalization. 16 This approach was indeed seen 428 in the US centers in our study, with a higher rate of leadless pacemakers implanted in the US, 429 and in patients who were severely or critically ill and in those who expired. In addition, a single 430 chamber pacemaker or Micra VVI were implanted in 55 (33.1%) patients, of whom 35(63.6%) 431 without a history of AF, and a significantly higher rate in patients who expired (56.3% vs 432 30.7%). This may reflect the implanting physician's attempt to minimize and shorten the 433 procedure in sicker patients. However, the implantations of leadless systems were not associated 434 with a lower complication rate. None of the differences in procedural technique was associated 435 with a higher mortality. The significantly higher rate of anesthesiologist used in procedures of 436 patients who expired likely reflected the physicians' perception of a sicker patient. 437

Due to the high mortality and complication rates observed in procedures performed in active 439 COVID-19 patients, permanent CIED implantations may be postponed when possible until 440 patient recovery when PPE will be unnecessary, and the procedure will not pose a risk to the 441 operator and supporting staff. This strategy may result in decreased complication rate and 442 possibly may also minimize costs. In urgent or emergent procedures, given the known 443 complications associated with TVP 30-32 and the resulting difficulty in handling such patients, a 444 definitive recommendation for preferring TVP and deferring permanent pacemaker implantation 445 cannot be given and should be made on an individual basis. Previous experience with procedures 446 in COVID-19 patients when PPE is used can lead to better preparation for future procedures, 447 such as use of antifog technology or powered air-purifying respirator (PPAR) suit. In the 448 occurrence of future pandemic, sharing personal experience between centers is beneficial. 449

This is a retrospective cohort study. As in some countries and continents only a single center 451 participated, the CIED procedure rate might not present an accurate estimation of the entire 452 country and continent. Although data originated from 13 different countries, it might not reflect 453 on procedural complication and mortality rate in other countries not participating in the study. In 454 addition, the centers choosing to participate are relatively large academic centers and may not 455 reflect on procedural complication and mortality in other smaller non-academic hospitals. In 456 addition, it is possible centers with very high complication rates may have declined participation. 457

Several centers could not provide the total number of hospitalized COVID-19 patients and 458 therefore results regarding implantation rate may vary; however, this was not the main goal of 459 the current study. 

The data underlying this article will be shared on reasonable request to the corresponding author. Single chamber PM 49 (29.5%) 44 (30.8%) 5 (21.7%) 43 (28.7%) 6 (37.5%) Dual chamber ICD 5 (3.0%) 4 (2.8%) 1 (4.3%) 5 (3.3%) 0 (0.0%) Single chamber ICD 5 (3.0%) 4 (2.8%) 1 (4.3%) 5 (3.3%) 0 (0.0%) CRTD/CRTP** 8 (4.2%) 7 (4.9%) 1 (4.3%) 8 (5.3%) 0 (0.0%) HIS pacing 1 (0.6%) 1 (0.7%) 0 (0.0%) 0 (0.0%) 1 (6.3%) MICRA VVI 6 (3.6%) 6 (4.2%) 0 (0.0%) 3 (2.0%) 3 (18.8%) MICRA AV 9 (5.4%) 7 (4.9%) 2 (8.7%) 6 (4.0%) 3 (18.8%) Replacements 7 (4.2%) 7 (4.9%) 0 (0.0%) 7 (4.7%) 0 (0.0%) SICD 2 (1.2%) 2 (1.4%) 0 (0.0%) 2 (1.3%) 0 (0.0%) 

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