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. 2022 Dec 1;17(12):e0276106. doi: 10.1371/journal.pone.0276106

The impact of COVID-19 pandemic on cardiac rehabilitation of patients following acute coronary syndrome

Feras Haskiah 1, Rana Jbara 2, Saar Minha 3,4, Abid Assali 4,5, Yaron Sela 6, David Pereg 4,5,*
Editor: Giuseppe Limongelli7
PMCID: PMC9714801  PMID: 36454912

Abstract

Background

Cardiac rehabilitation improves prognosis and symptoms in cardiac patients. In 2020, due to the COVID-19 pandemic, cardiac rehabilitation services were temporarily suspended between April and August. We aimed to investigate the effect of cardiac rehabilitation suspension during the COVID-19 pandemic on patients’ exercise capacity and metabolic parameters.

Methods

Included were patients undergoing cardiac rehabilitation following hospital admission for ACS. Exercise capacity, weight and body fat percentage were compared between baseline, pre- and post-lockdown visits.

Results

A total of 281 patients participated in the cardiac rehabilitation program prior to its suspension. Of them, only 198 (70%) patients returned to the program on its renewal and were included in the analysis. Exercise capacity improved significantly in the pre-lockdown stress test compared to baseline. However, there was a significant decrease in exercise capacity in the post compared to pre-lockdown test (8.1±6.3 and 7.1±2.1 METs in pre- and post-lockdown measurements, respectively, p<0.001). Of the 99 (50%) of patients that demonstrated at least 10% improvement in exercise capacity in the pre-lockdown test, 48(48.5%) patients returned to their baseline values in the post-lockdown test. Post-lockdown assessment demonstrated a significant weight gain (80.3 and 81.1kg, in pre- and post-lockdown measurements, respectively, p<0.001) as well as an increase in visceral fat level and body fat percentage.

Conclusions

Cardiac rehabilitation suspension for 4 months during COVID-19 pandemic caused a significant reduction in exercise capacity and increased weight and body fat percent. These findings highlight the importance of remote cardiac rehabilitation services that can continue uninterrupted in times of pandemic.

Introduction

Exercise based cardiac rehabilitation improves prognosis and quality of life of patients with coronary artery disease [1–3]. Accordingly, it is strongly recommended by all international guidelines for patients following hospitalization for acute coronary syndrome [4–7]. The main goals of cardiac rehabilitation programs are adequate risk factor control, optimizing lifestyle and improving exercise capacity [3]. Regular uninterrupted attendance of patients is very important in order to achieve maximal improvement in exercise capacity and better clinical outcomes [8, 9].

On January 30, 2020, the World Health Organization announced the outbreak of a new Corona virus. Soon after, the COVID-19 outbreak in China progressed into a worldwide pandemic [10, 11]. First cases of confirmed COVID-19 infections were reported in Israel in February 2020 and subsequently the Israeli government and health authorities implemented an escalating social distancing policy that led to several successive lockdowns. Moreover, the official recommendation for patients at high risk for severe COVID-19 infection (including elderly patients and those with cardiovascular comorbidities) was to remain in quarantine even between lockdowns [12, 13]. As a result, cardiac rehabilitation services were temporarily suspended between April and August 2020.

The aim of our study was to evaluate the effect of cardiac rehabilitation suspension for 4 months during the Covid-19 pandemic on the exercise capacity of patients participating in a cardiac rehabilitation program.

Methods

This is an observational retrospective study that was conducted in the Cardiac Rehabilitation Center at the Meir Medical Center. Included were patients with a history of hospital admission due to acute coronary syndrome (ACS) who had been participating in the cardiac rehabilitation program for at least 3 months prior to the program suspension in April 2020.

A cardiac rehabilitation program for patients with acute coronary syndrome usually begins 4–6 weeks following hospital discharge and all costs are fully covered by the governmental medical insurance for 9 months. The exercise program consists of two outpatient sessions per week and a customized physical training program that is tailored for each patient under the guidance and supervision of a physiologist and a large staff of physical instructors. Each exercise session starts with a 5-minute warm-up, lasts 60 minutes and ends with a 5-minute cooling and stretching period. Exercise modalities vary between upper body ergometer, cycle ergometer, treadmills, stair climbers and light resistance exercises. During exercise sessions different modalities are combined according to indication and contra-indications established by biomechanical evaluation, adherence level to physical activity and musculoskeletal comorbidities. For each patient, physical activity intensity level is controlled and adjusted with the help of the Borg Rating of Perceived Exertion Scale (RPE scale; numbered from 6 to 20) [14]. Besides physical training, the cardiac rehabilitation program includes psychosocial support, nutritional and lifestyle consultations. The cardiac rehabilitation program includes a complete assessment by a cardiologist at baseline and then every 3 months. This includes clinical assessment, the evaluation of exercise capacity and the measurement of weight, body fat percentage, and visceral fat level.

Exercise capacity was evaluated by a routine treadmill stress test using either Bruce or low-fit Bruce exercise protocols at baseline and then routinely every 3 months. Results from stress tests were documented by the supervising exercise physiologist or physician. Stress tests and metabolic equivalent (METs) evaluation were performed according to the American Heart Association Standards for Testing and Training [15, 16].

Weight, body fat percentage and visceral fat level were measured at baseline, and then routinely every 3 months using the Omron Karada Scan HBF511 (Omron Health Care, Kyoto, Japan) bioimpedance device (BIA) [17]. BIA is a noninvasive method for body composition assessment. After entering age, gender and height, patients were asked to stand on the device after its calibration. The measurements were held before the exercise sessions in order to avoid dehydration that may affect the accuracy of this method. The BIA measured the visceral fat level in the range from 1 to 59 (low to high level) [18, 19]. A higher level indicated more visceral fat.

The primary endpoint of our study was the rate of at least 10 or 25% improvement in exercise capacity in pre and post lockdown exercise test compared to baseline [20]. Secondary endpoints included the effect of cardiac rehabilitation suspension on weight, body fat percentage, and visceral fat level as well as LDL-cholesterol levels.

Clinical, laboratory and demographic data were extracted from the electronic medical records of Meir Medical center.

The study was approved by the Meir Medical center Institutional Ethics Committee in keeping with the principles of the Declaration of Helsinki. In accordance with Ministry of Health regulations, the Institutional Ethics Committee did not require written informed consent because data were collected anonymously from the electronic medical records without active patient participation.

Statistical analysis

Descriptive statistics were performed using means and standard deviations for the continuous variables, and frequencies for the discrete variables. Univariate comparisons for repeated measures were performed using Friedman and Wilcoxon signed ranks test. Tests between independent samples were done using the Mann-Whitney test. Significance was considered for a p-value lower than 5%. Data were analyzed using SPSS software version 25.

Results

A total of 281 patients participated in the cardiac rehabilitation program for at least 3 months prior to its suspension in April 2020. Of them, only 198 (70%) patients returned to the program on its renewal on August 2020 and were included in the analysis. In 75 of the 83 patients (90%) who did not return to cardiac rehabilitation at its renewal, the reason was patients’ preference to maintain social distancing due to their concerns regarding Covid-19 contagion. Participants had a median age of 67.9±9.8 years and included 65 (32.8%) women. Table 1 presents baseline demographic and clinical characteristics of the study participants at the first cardiac rehabilitation appointment.

Table 1. Baseline patient characteristics and clinical factors.

Demographic Characteristics N = 198
Sex
 • Male 133(67.2%)
Age (years) 67.9±9.8
 • < 65 67(33.8%)
 • ≥ 65 131(66.2%)
Baseline Measurements
Height (cm) 169.7±9.3
Weight (kg) 81.5±15.7
BMI (kg/m2) 28.2±4.5
BMI ≥30 63(31.8%)
Body fat percentage (%) 30.5±8.8
Visceral fat level 12.9±4.7
Clinical Characteristics
Dyslipidemia 152(76.8%)
Diabetes mellitus 72(36.3%)
Cigarette smoking 55(27.8%)
Family history of CAD 61(30.8%)
Atrial fibrillation 29(14.6%)
PVD 15(7.5%)
Heart Failure 31(15.6%)
Systolic Function:
 • Normal 113(57.1%)
 • Mild dysfunction 28(14.1%)
 • Moderate dysfunction 36(18.2%)
 • Severe dysfunction 5(2.5%)
PCI 166(83.8%)
CABG 43(21.7%)
Medication
Aspirin 157(79.2%)
P2Y12 inhibitors 85(42.9%)
Statins 166(83.8%)
Ezetimibe 50(25.3%)
PCSK9 inhibitors 8(4%)
Blood Tests at baseline
Total Cholesterol (mg/dl) 147.5±42
Triglyceride (mg/dl) 135.4±68
LDL-C(mg/dl) 76.2±31
HDL-C (mg/dl) 44.3±11.4
HbA1C (%) 6.2±0.9
Hemoglobin (g/dl) 13.8±1.5
Creatinine (mg/dl) 0.98±0.2

Values are mean ± standard deviation or N (%).

BMI-body mass index; CAD-coronary artery disease; PVD-peripheral vascular disease; PCI-percutaneous coronary intervention; CABG-Coronary artery bypass graft surgery; PCSK9- Proprotein convertase subtilisin/kexin type 9; LDL-C-low density lipoprotein cholesterol; HDL-C-high density lipoprotein cholesterol; HbA1C-HemiglobinA1C

Exercise capacity improved significantly in the pre-lockdown stress test compared to baseline (6.9±2.1 and 8.1±6.3 METs, p<0.001) (Fig 1). Accordingly, at least 10 or 25% improvement in exercise capacity was achieved by 50% and 17.7% of patients in the pre-lockdown compared to the baseline stress test. However, stress test on the resumption of cardiac rehabilitation following the end of the lockdown demonstrated a significant decrease in exercise capacity compared to the last pre-lockdown test (8.1±6.3 and 7.1±2.1 METs in pre- and post-lockdown measurements, respectively, p<0.001). Among the 99 (50%) patients who achieved at least 10% improvement in exercise capacity in the pre-lockdown stress test, only 48(48.5%) maintained this improvement in the post-lockdown stress test. Similar findings were demonstrated in the 17.7% patients who achieved at least 25% improvement in exercise capacity in the pre-lockdown stress test. This improvement was maintained by only `13 (37%) patients (Fig 2).

Fig 1. Exercise capacity at baseline, pre-lockdown, and post lock down measurements (n = 198).

Fig 1

Fig 2. Flow chart of the study participants including changes in exercise capacity (n = 198).

Fig 2

Participation in the cardiac rehabilitation program resulted in a significant mean weight reduction (81.5kg and 80.3kg in baseline and pre-lockdown measurement respectively, p<0.001) (Table 2). However, cardiac rehabilitation suspension resulted in a significant weight gain (80.3kg vs 81.1kg, in pre- and post-lockdown measurements respectively, p<0.001). Similar patterns were demonstrated for body fat percentage and visceral fat level (Table 2). Cardiac rehabilitation suspension had no effect on patients’ lipid profile. Not surprisingly, albeit not statistically significant, LDL-cholesterol reduction was demonstrated in the pre-lockdown test followed by further consistent reduction during cardiac rehabilitation suspension (Table 2), suggesting adequate adherence to lipid lowering therapy during this period.

Table 2. Secondary endpoints at baseline, pre-lockdown, and post lock down measurements.

Secondary Endpoint Baseline Pre-lock down Post-lock down P-value
Body Weight (kg) 81.5±15.7 80.3±15.3 81.1±15.7 <0.001*
BMI (kg/m2) 28.2±4.5 27.7±4.3 28.2±4.6 <0.001*
Body Fat Percentage (%) 30.5±8.8 29.5±8.8 30.1±8.9 <0.001*
Visceral Fat Level 12.9±4.7 12.3±4.5 12.7±4.7 <0.001*
LDL-C (mg/dl) 76.2±31 72.1±30.1 67.8±30 0.35*

Values are mean± SD

BMI-body mass Index; LDL-C -low-density lipoprotein c

*P-values are both for the comparison between baseline and pre-lockdown measurements and between pre and post lockdown measurements

Discussion

The current study investigated the effect of cardiac rehabilitation suspension during the COVID-19 pandemic on exercise capacity and metabolic parameters of the participants. We demonstrated that 30%(n = 83) of patients did not return to the cardiac rehabilitation at its renewal. Among patients who did return, the 4-month suspension was associated with a significant reduction of exercise capacity, a significant weight gain and increased body fat percentage and visceral fat level. On the other hand, cardiac rehabilitation suspension had no effect on LDL-cholesterol levels.

Exercise based cardiac rehabilitation improves outcomes and quality of life of patients following hospitalization for acute coronary syndrome [1–3]. Patients’ adherence to cardiac rehabilitation programs has been associated with a lower risk of adverse outcomes and improved exercise capacity. A recent large meta-analysis demonstrated the dose-response association between cardiac rehabilitation session attendance or dose and reduced risk of major adverse cardiovascular events including death [21]. A continuous increase of 1 session in an uninterrupted cardiac rehabilitation program was significantly associated with a 1% to 2% reduction in major adverse cardiovascular event risk. Lack of adherence to cardiac rehabilitation may have several causes, including low patient compliance and concurrent acute cardiac and non-cardiac conditions. The COVID-19 pandemic has caused a major disruption to the delivery of routine health care across the world. Cardiac rehabilitation programs across Israel have temporarily suspended in-person services as a result of large-scale physical distancing recommendations designed to flatten the COVID-19 pandemic curve. We demonstrated that a 4-month cardiac rehabilitation suspension eliminated most of the improvement in exercise capacity and metabolic parameters that had been achieved in the preceding months. Interestingly, we observed a consistent reduction in LDL-cholesterol levels during cardiac rehabilitation suspension, suggesting adequate adherence to lipid lowering therapy during this period. To the best of our knowledge, the current study is the first report on the effect of cardiac rehabilitation suspension during COVID-19 pandemic on patients with coronary artery disease.

Several studies have demonstrated that the lockdown and social distancing caused by the worldwide COVID-19 pandemic may influence common health behaviors including decreased daily physical activity and increased sedentary time [22, 23], unhealthy diet and increased body mass and obesity [24, 25]. These patterns have been demonstrated in different populations, including in patients with cardiovascular diseases [26]. Accordingly, it has been recommended to consider different strategies to allow home based physical activity programs [27, 28]. In recent years there has been a growing worldwide interest in remote cardiac rehabilitation programs using various technologies. Remote cardiac rehabilitation was found to be an effective, cost-efficient alternative delivery model that could function as a complement to existing services, improve overall utilization rates by increasing reach and satisfying unique participant preferences [29, 30]. Indeed, remote cardiac rehabilitation has been suggested as an effective alternative to outpatient cardiac rehabilitation in the COVID-19 pandemic era [31]. Our findings highlight the importance of remote cardiac rehabilitation especially in these days of social restrictions. Recently, we have successfully initiated such a program in our medical center.

The current study has several limitations that merit consideration. First, similar to most studies on patients in cardiac rehabilitation, there is an inherent selection bias since patients who did not attend cardiac rehabilitation for various reasons (poor compliance, orthopedic comorbidities, social issues etc.) were not represented in the analysis. Second, exercise capacity was assessed by a regular treadmill stress testing, and we did not include a metabolic test (VO2 max) or evaluate muscle or vascular function. Third, we did not have data regarding the level of physical activity and dietary habits during cardiac rehabilitation suspension. Finally, we present the experience of a single cardiac rehabilitation center, and the cohort size is relatively modest. Therefore, our findings should be extrapolated to other populations with caution.

In conclusion, cardiac rehabilitation suspension for 4 months during COVID-19 pandemic was associated with a significant dropout of patients and reduction in exercise capacity and increased body mass and fat percent in the remaining participants. These findings highlight the importance of remote cardiac rehabilitation services that can continue uninterrupted in times of pandemic.

Supporting information

S1 Data

(XLSX)

Data Availability

All relevant data are within the paper and its Supporting information files.

Funding Statement

The author(s) received no specific funding for this work.

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Decision Letter 0

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23 Jun 2022

PONE-D-22-14087The Impact of Covid-19 Pandemic on Cardiac Rehabilitation of patients following acute coronary syndrome.PLOS ONE

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1) While the paper is within the word limit, I feel that readability would be enhanced by being more succinct and shortening the word count.

2) The authors should provide a more specific definition of the primary endpoint. The present definition ("The primary endpoint was the effect of cardiac rehabilitation suspension during COVID-19 pandemic on exercise capacity of the participants") appears too general.

3) The authors report that "tests between independent samples" were used. Independent sample tests are used to compare independent groups. Based on the study design, this approach does not seem correct for the analysis.

4) The sample size is relatively modest to offer robust evidence on the topic.

5) The authors should provide detailed information regarding all the reasons for not returning to cardiac rehabilitation.

6) The study population consisted of patients with previous acute coronary syndrome. Yet, only 79% of patients received aspirin. What were the reasons for not prescribing aspirin in the remaining 21% of cases? The same reasoning also apply to the prescription of statins.

7) The manuscript presentation, including the graphical presentation, should be substantially improved.

Reviewer #2: The manuscript by Prof. David Pereg and Colleagues analysed the impact of the COVID-19 pandemic on a cardiac rehabilitation program of coronary patients.

Briefly, the Authors found that cardiac rehabilitation (CR) suspension for 4 months during the COVID-19 pandemic caused a significant reduction in exercise capacity and increased weight and body fat percent highlighting the unmet need for specific remote measures to ensure better follow up strategies.

Currently, direct evidence on the impact of COVID-19 on CV rehabilitation programs is still limited and, for this reason the study is welcome. Although concise and clearly written, one may wonder if a more in-depth analysis on the present data could be performed to identify those patients at highest risk of losing CR benefit.

Please find my comments below.

Major Comments.

1. A total of 198/281 patients who were initially referred for CR returned for program continuation. Of the 99 patients who had achieved >10% improvement in exercise capacity, only 48 maintained this improvement. It would be interesting to acknowledge which factors were associated with lack of improvement (age, gender, BMI, baseline METs, LVEF, social factors?). A focus on this group could be helpful for the attending physician or nurse for future counselling. A logistic regression model could be a simple tool to assess this topic.

2. It is sometimes difficult to understand how the final population was derived and how many improved exercise capacity. A flowchart of the study population (even as supplementary material) could be useful.

3. In lines 157-159, Authors briefly refer to gender and age specific differences, however no quantitative data is reported. My suggestion is to either add data in the tables or remove the information altogether.

4. LDL concentrations seem to decrease through time although Authors highlight the lack of statistical significance. What test did they use? Was it a repeated measure test? By looking at the numbers the trend may seem significant.

5. A clearer presentation of the baseline vs. pre-lockdown vs. post lock-down characteristics of the study population could be useful: restructuring Table 2 to include trends of variables like body weight, BMI (and BMI >30), METs, etc. would be informative and may identify potential topics which could be amenable of future improvement.

Minor comments.

1. Introduction: The introduction paragraph has too many references (20).

2. Methods: the study design has not been reported.

3. Methods: a reference for the 10% cut-off to consider capacity improvement could be useful.

4. Tables: please add measurement units whenever missing and at least 1 decimal.

5. Table 1: how many patients were obese?

6. Table 1: do the Authors have echocardiographic information?

7. Table 1: PVD abbreviation is for PAD?

8. Figure 1: please add number of patients.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Carlo Fumagalli, MD

**********

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PLoS One. 2022 Dec 1;17(12):e0276106. doi: 10.1371/journal.pone.0276106.r002

Author response to Decision Letter 0


19 Jul 2022

July,15,2022

Giuseppe Limongelli

Academic Editor

PLOS ONE

Ms. Ref. No.: PONE-D-22-14087

The Impact of Covid-19 Pandemic on Cardiac Rehabilitation of patients following acute coronary syndrome.

We thank the reviewers and you for the thorough review of our manuscript. We read the comments carefully and have revised the manuscript accordingly. Our responses to the comments are detailed below. We hope that you will find the revised manuscript suitable for publication in PLOS ONE.

.

Sincerely yours,

David Pereg, MD

Prof David Pereg, CICU director, Division of Cardiology, Meir Medical Center.

59 Tchernichovsky St, Kfar-Saba, 44281, Israel.

Tel: +972-9-7472587, Fax- +972-9-7472812. Email: davidpe@tauex.tau.ac.il

Response to Reviewer #1

Comment #1:

While the paper is within the word limit, I feel that readability would be enhanced by being more succinct and shortening the word count.

Our response: Done.

Comment #2:

The authors should provide a more specific definition of the primary endpoint. The present definition ("The primary endpoint was the effect of cardiac rehabilitation suspension during COVID-19 pandemic on exercise capacity of the participants") appears too general.

Our response: Done. See lines 106-107 in the revised manuscript:

"The primary endpoint of our study was the rate of at least 10 or 25% improvement in exercise capacity in pre and post lockdown exercise test compared to baseline. "

Comment #3:

The authors report that "tests between independent samples" were used. Independent sample tests are used to compare independent groups. Based on the study design, this approach does not seem correct for the analysis.

Our response:

Indeed, most of the primary analyses are dependent samples, and therefore we conducted Friedman and Wilcoxon signed ranks test. However, several comparisons were made between independent groups, such as males vs. females. We refer also to these comparisons.

Comment #4:

The sample size is relatively modest to offer robust evidence on the topic.

Our response:

We completely agree with this comment. The "study limitation" paragraph has been revised accordingly. Discussion section line 229-231: " Finally, we present the experience of a single cardiac rehabilitation center and the cohort size is relatively modest. Therefore, our findings should be extrapolated to other populations with caution."

Comment #5:

The authors should provide detailed information regarding all the reasons for not returning to cardiac rehabilitation.

Our response:

This comment is very well taken. Overall, 83 (30%) patients did not return to cardiac rehabilitation at its renewal. In 75 patients (90%) the reason for not returning to cardiac rehabilitation was patients' preference to maintain social distancing due to their concerns regarding Covid-19 contagion. This important information has been added to the results section of the revised manuscript.

Result section, lines 128-130: " In 75 of the 83 patients (90%) who did not return to cardiac rehabilitation at its renewal, the reason was patients' preference to maintain social distancing due to their concerns regarding Covid-19 contagion. "

Comment#6:

The study population consisted of patients with previous acute coronary syndrome. Yet, only 79% of patients received aspirin. What were the reasons for not prescribing aspirin in the remaining 21% of cases? The same reasoning also apply to the prescription of statins.

Our response:

This comment is very well taken. Table 1 presents baseline medical therapy that was reported by the patients at the initiation of cardiac rehabilitation. In some cases, changes in therapy were made by the cardiac rehabilitation team during the rehabilitation period. The study population consisted of patients following hospital admission due to ACS. While aspirin is an integral part of the treatment of patients with ACS, there are several exceptions including patients with an indication for anticoagulation (atrial fibrillation, apical thrombus etc.) who are usually treated with a combination of an anti-coagulant and either aspirin or clopidogrel). Indeed, 15% of our study population had concomitant atrial fibrillation. Another group of patients who may not be treated with aspirin include those with MI with normal coronary arteries (MINOCA) who may be discharged with a single antiplatelet therapy. Regarding lipid lowering therapy, 88% of patients were treated with either statin or PCSK-9 inhibitors prior to initiation of cardiac rehabilitation.

Comment #7:

The manuscript presentation, including the graphical presentation, should be substantially improved.

Our response: Done.

Response to Reviewer #2

Comment#1:

A total of 198/281 patients who were initially referred for CR returned for program continuation. Of the 99 patients who had achieved >10% improvement in exercise capacity, only 48 maintained this improvement. It would be interesting to acknowledge which factors were associated with lack of improvement (age, gender, BMI, baseline METs, LVEF, social factors?). A focus on this group could be helpful for the attending physician or nurse for future counselling. A logistic regression model could be a simple tool to assess this topic

Our response:

We thank the reviewer for addressing this important point. Accordingly, we have performed a logistic regression model. However, none of the baseline characteristics was found to be an independent predictor for lack of improvement.

Comment#2:

It is sometimes difficult to understand how the final population was derived and how many improved exercise capacity. A flowchart of the study population (even as supplementary material) could be useful.

Answer#2:

We thank the reviewer for this comment. A flowchart has been added to the revised manuscript accordingly- see figure 2 in the revised manuscript.

Comment#3:

In lines 157-159, Authors briefly refer to gender and age specific differences, however no quantitative data is reported. My suggestion is to either add data in the tables or remove the information altogether.

Our response: Done. The relevant sentence has been removed.

Comment#4:

LDL concentrations seem to decrease through time although Authors highlight the lack of statistical significance. What test did they use? Was it a repeated measure test? By looking at the numbers the trend may seem significant

Our response:

Consistent with all of the similar analyses, we also conducted repeated measure test to examine the effect on LDL. The significance of this analysis (p=.35) was not determine as significant (p<.05) or marginal significant (p<.10).

Comment#5:

A clearer presentation of the baseline vs. pre-lockdown vs. post lock-down characteristics of the study population could be useful: restructuring Table 2 to include trends of variables like body weight, BMI (and BMI >30), METs, etc. would be informative and may identify potential topics which could be amenable of future improvement.

Our response: Data regarding BMI, body weight, body fat percentage, visceral fat level and LDL-C are presented in thabe-2. Data regarding exercise capacity are presented in figure 1.

Minor Comments:

Comment#1:

Introduction: The introduction paragraph has too many references (20).

Our response: We removed several references accordingly.

Comment#2:

Methods: the study design has not been reported

Our response:

This was an observational retrospective study. We have added this information to the methods section. (Line 69)

Comment#3:

Methods: a reference for the 10% cut-off to consider capacity improvement could be useful.

Our response: Done. (Reference 20 in the revised manuscript)

Comment#4

Tables: please add measurement units whenever missing and at least 1 decimal.

Our response: Done.

Comment#5:

Table 1: how many patients were obese?

Our response:

63 patients had a BMI > 30 at baseline. This information has been added to table 1.

Comment#6:

Table 1: do the Authors have echocardiographic information?

Our response:

Data regarding the left ventricular systolic function at baseline are presented in table-1.

Comment#7:

Table 1: PVD abbreviation is for PAD?

Answer#7

Table 1 has been corrected accordingly.

Comment#8:

8. Figure 1: please add number of patients.

Answer#8 :

The number of patients has been added to the figure legend.

[20] Haskiah F, Shacham Y, Minha S, Rozenbaum Z, Pereg D. CHA2DS2-VASc score and exercise capacity of patients with coronary artery disease participating in cardiac rehabilitation programs. Coron Artery Dis. 2017;28(8):697-701.

Decision Letter 1

Giuseppe Limongelli

29 Sep 2022

The Impact of Covid-19 Pandemic on Cardiac Rehabilitation of patients following acute coronary syndrome.

PONE-D-22-14087R1

Dear Dr. Pereg,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Giuseppe Limongelli

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have addressed all the comments of the Editors and Reviewers.

I have not further comments.

Reviewer #2: I thank the Authors of ‘The Impact of Covid-19 Pandemic on Cardiac Rehabilitation of patients following acute coronary syndrome’ for acknowledging all the points raised during the reviewing process.

Although the limitations due to the sample size and the difficulty in extrapolating potential factors associated with benefit (or lack thereof) of cardiac rehabilitation during the COVID-19 pandemic may limit generalizability, the results of the report are still of interest.

The Authors may want to report the lack of associated factors with maintained improvement in the Results section and Discussion/Limitations paragraph.

Minor comments.

Please amend all percentages to the first decimal point in figures and tables.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

Acceptance letter

Giuseppe Limongelli

22 Nov 2022

PONE-D-22-14087R1

The Impact of Covid-19 Pandemic on Cardiac Rehabilitation of patients following acute coronary syndrome.

Dear Dr. Pereg:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Giuseppe Limongelli

Academic Editor

PLOS ONE

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    This section collects any data citations, data availability statements, or supplementary materials included in this article.

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    S1 Data

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    Data Availability Statement

    All relevant data are within the paper and its Supporting information files.


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