key: cord-0929051-zi9p4ei1
authors: Orso, Francesco; Herbst, Andrea; Migliorini, Marta; Ghiara, Camilla; Virciglio, Simona; Camartini, Viola; Tognelli, Silvia; Lucarelli, Giulia; Fortini, Giacomo; Pratesi, Alessandra; Di Bari, Mauro; Marchionni, Niccolò; Ungar, Andrea; Fattirolli, Francesco; Baldasseroni, Samuele
title: Telehealth management and risk stratification of older patients with chronic heart failure during COVID-19 pandemic: prognostic evaluation of the TeleHFCovid19-Score.
date: 2021-12-24
journal: J Am Med Dir Assoc
DOI: 10.1016/j.jamda.2021.12.024
sha: 5fe83ab7a6889916170122a344f2d426051de107
doc_id: 929051
cord_uid: zi9p4ei1

Objectives To evaluate six-month risk stratification capacity of the newly developed TeleHFCovid19-Score for remote management of older patients with heart failure (HF) during Coronavirus disease 2019 pandemic. Design Monocentric observational prospective study. Setting and Participants Older HF outpatients remotely managed during the first pandemic wave. Methods The TeleHFCovid19-Score (0-29) was obtained by an ad hoc developed multiparametric standardized questionnaire administered during telephone visits to older HF patients (and/or caregivers) followed at our HF clinic. Questions were weighed on the basis of clinical judgment and review of current HF literature. According to the score, patients were divided in progressively increasing risk groups: green (0-3), yellow (4-8) and red (≥9). Results 146 patients composed our study population: at baseline, 112, 21 and 13 were classified as green, yellow, and red respectively. Mean age was 81±9 years, females were 40%. Compared to patients of red and yellow groups, those in the green group had a lower use of high dose loop diuretics (p<0.001) or thiazide-like diuretics (p=0.027) and had reported less frequently dyspnea at rest or for basic activities, new/worsening extremities oedema or weight increase (all p<0.001). At six months, compared to red (62.2%) and yellow patients (33.3%), green patients (8.9%) presented a significantly lower rate of the composite outcome of cardiovascular death and/or HF hospitalization (p<0.001). Moreover, ROC analysis showed a high sensibility and specificity of our score at six months (AUC =0.789, 95% CI 0.682-0.896, p<0.001) with a score <4.5 (very close to green group cut-off) that identified lower-risk subjects. Conclusion and implication The TeleHFCovid19-Score was able to correctly identify patients with mid-term favorable outcome. Therefore, our questionnaire might be used to identify low-risk chronic HF patients which could be temporarily managed remotely, allowing to devote more efforts to the care of higher-risk patients which need closer and on-site clinical evaluations.

To address the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, during 32 spring 2020 many governments imposed a total lockdown to reduce interpersonal contact and, hence, 33 the risk of diffusion. Furthermore, the access to outpatient services for the management of chronic 34 diseases, such as heart failure (HF), was also strongly limited. Despite discordant evidence regarding 35 the effectiveness of telemedicine for the management of HF (e.g., quality of life improvement with 36 mild or neutral impact on hospitalizations and no significant effect on mortality) 1-7 , clinicians were 37 forced to organize telephone visits or tele-monitoring, with the purpose of maintaining the delivery 38 of care from remote instead of in-person visits, and this approach was encouraged by international 39 cardiological societies 8 . Therefore, due to the absence of standardized tools we rapidly developed a 40 multiparametric questionnaire (from which we derived the TeleHFCovid19-Score), suitable for 41 telephone administration to older HF patients and/or their caregivers 9 . This questionnaire was 42 designed to assess the clinical stability and social isolation impact on health status of the nearly 150 43 patients we were taking care for at our outpatient HF clinic by that time 9 . The aim of the present study 44 was to evaluate the six months prognostic ability of the TeleHFCovid19-Score during the first months 45 of the coronavirus disease 2019 (COVID-19) pandemic. In a post pandemic setting, where a rationale 46 utilization of healthcare resources is strongly needed, a prognostic score may help to appropriately 47 triage chronic HF patients and, accordingly, manage them in person or remotely. 48

The study design, the development of the questionnaire and the derived TeleHFCovid19-Score, as 50 well as the preliminary results of implementation in the first 30 patients, have been previously 51 published in this journal 9 . Briefly, starting from April 2020, we administered the questionnaire to all 52 patients we were taking care of and/or to their caregivers, during scheduled telephone contacts, which 53 were formally recorded through hospital's administrative program as teleconsulting evaluations. In 54 accordance with Italian privacy laws, the questionnaire was anonymized, and patients were identified 55 by a numeric code, date of birth and gender. Selected questions were weighted on the basis of clinical 56 judgment and review of current HF literature and the final version of the questionnaire was approved 57 after collegial discussion and agreement of all authors using the Delphi method 10 . For the present 58 study the score was calculated based on data collected during the phone interview. For blood tests the 59 last evaluations (prior to phone contact) were considered and compared to previous results in order 60 to analyze variations. Figure 1 shows the questionnaire with single questions score assignment, 61 calculation of the TeleHFCovid19-Score and consequent color risk score group designation: green 62 (0-3), yellow (4-8), or red (≥9). The color code also determined the timing of next phone contact at 63 one, two or four weeks for the red, yellow, and green groups, respectively. However, all patients were 64 systematically contacted at one, three and six months to assess vital status and record potential events 65 (hospitalization and death). The primary study outcome was a composite of death from cardiovascular 66 (CV) causes and/or hospitalization for HF at six months, which individually were secondary 67 outcomes. The study conformed to the Declaration of Helsinki 11 and was approved by the local 68 institutional review board. 69

Statistical analysis was performed using SPSS® v.27 package (SPSS, Inc., Chicago, IL). 70

Continuous variables were expressed as mean ± standard deviation and categorical variables as 71

percentages. Data were compared across the three-color code groups using ANOVA test and the chi-72 square test, as appropriate. The sensitivity and specificity of the TeleHFCovid19-Score questionnaire 73 J o u r n a l P r e -p r o o f in the prediction of study outcomes was tested with the Receiver Operating Characteristic (ROC) 74 analysis. A p value <0.05 was considered statistically significant. 75

We enrolled 146 patients. After baseline questionnaire administration, according to the 77 TeleHFCovid19-Score, 112, 21 and 13 patients were assigned to the green, yellow, and red groups, 78 respectively. Demographic and clinical characteristics of the study population, including principal 79 CV and non-CV comorbidities and treatments, are summarized in Table 1 . Mean age of the study 80 population was 81±9 years with a 40% prevalence of females. Almost a third of the study population 81 was represented by patients with HF with reduced ejection fraction and an ischemic aethiology was 82 reported in ~ 50% of patients. Moreover, in keeping with the advanced age of the patients enrolled 83

we found a high prevalence of main CV and non-CV comorbidities. As shown in Table 1 , there were 84 no significant differences in terms of demographic and clinical characteristics among the three-color 85 risk groups. Among pharmacological treatments, we observed a high prescription rate of oral 86 anticoagulants, as a consequence of the prevalence of the history of atrial fibrillation, of renin 87 angiotensin aldosterone inhibitors (with almost a quarter of the study population treated with 88 sacubitril/valsartan) and betablockers. Among pharmacological treatments shown in Table 1  89 betablockers prescription was the only one which varied significantly across the three groups being 90 less prescribed in the yellow intermediate risk group. 91

Answers to questionnaire regarding clinical condition, blood tests, adherence to 92 recommendations and treatments are reported in Table 2 . We observed a lower rate of previous acute 93 HF hospitalizations as well as of the need to increase diuretic therapy since former clinical evaluation 94 in green than in yellow and red groups (p<0.001). In all study population a high prevalence of self-95 reported adherence to pharmacological treatments including guidelines directed medical treatments 96 and diuretics, as well as behavioral measures (regular assessment of blood pressure, heart rate and 97 body weight and water restriction) were observed. Moreover, we found significant differences across 98 the three groups regarding the use of high dose of loop diuretics (p<0.001) and metolazone (p=0.027), 99 progressively more frequent from green to yellow and red groups. Similarly, after completing the 100 questionnaire-guided telephone interview, the doses of loop diuretics were increased or thiazide/thiazide like diuretics for sequential nephron blockade were prescribed more frequently to 102 red code patients (p<0.001). Furthermore, all signs and symptoms potentially related to the severity 103 of HF and/or of heart disease were progressively worse from green to red coding. Higher levels of 104 creatinine and NT-proBNP were also found in the red group than in the green and yellow ones (both 105 p=0.002). 106

At six-month follow-up 20 patients (13.7%) had died and 32 (21.9%) had been hospitalized. 107

The one, three and six months primary composite outcome rates of CV death and/or HF 108 hospitalization were 8.2%, 11% and 17.8% respectively. The difference in the primary outcome and 109 its components occurrence in the color groups at one, three and six months are shown in Figure 2 . 110 Patients coded as green had a significantly lower incidence of the primary composite outcome 111 compared to those in the yellow and red groups, therefore confirming the capacity of the 112

TeleHFCovid19-Score to correctly stratify the risk of serious events. Analyzing in detail the 113 components of the primary outcome, we found a significant difference among the three-color groups 114 at all follow-up timing intervals both for CV death and HF hospitalizations resulting significantly 115 lower in patients coded at baseline as green. 116

Furthermore, to confirm the clinical predictive validity of the cut-offs used to define the 117 different color-coding risk groups, we used a ROC curve analysis. Our score demonstrated a very 118 good power in predicting the composite of CV mortality and/or hospitalizations for HF, both at short-119 and at medium-terms, with a high area under the curve (AUC) at all three FU intervals ( Figure 3) ; 120 furthermore, a score of 4.5 corresponded to the cut-off with the best sensitivity to specificity 121 relationship for identifying low-risk chronic HF patients, at one, three and six months. 122

The main results of our study may be summarized as follows: 124 -COVID-19 pandemic has forced health care providers to change their way of managing chronic 125 disease. 126 -Our newly developed TeleHFCovid19-Score generated by a phone interview questionnaire at the 127 beginning of the pandemic emergency was able to correctly stratify the risk of adverse events in 128 elderly ambulatory HF patients. At present, SARS-CoV-2 pandemic is still forcing physicians to play out new methods to manage "at 138 a distance" patients affected by chronic diseases such as HF, to limit the accesses to hospital and 139 outpatient clinics 12-14 . In Great Britain during the peak of the first pandemic wave, probably as a 140

consequence of social distancing measures or contagion fear, a dramatic reduction of HF 141 hospitalizations has been reported as well as more severe symptoms upon admission in hospitalized 142 patients 15 . Similar data were observed also in other countries, like Italy 16-17 . Because of this difficult 143 situation, international societies have invited physicians to play out strategies of virtual or telephone 144 visits for the management of chronic diseases 8 . Therefore, we created a standardized questionnaire to 145 be administered during a simple telephone visit (median time of administration 7 minutes), instead of 146 a real virtual visit for the difficulties that many of our older patients presumably would have had in 147 computer/tablets management. Our TeleHFCovid19-Score generated from the structured questionnaire allowed us to identify low-, intermediate-and high-risk patients who were then grouped 149 by an easily usable color coding as green, yellow and red. Based on color group coding, we also 150 modified the intervals of scheduled phone contact at 4, 2 and 1 week, respectively, or we 151 recommended hospital evaluation. To our knowledge, this represents one of the few examples of a 152 telephone visit score for the management of chronic HF patients proposed during COVID-19 153 pandemic, especially for older patients. 154

Through differently scheduled phone contacts, we were able to guarantee continuity of care 155 to our patients and timing adjustments to HF medical therapies by acting both on diuretics and 156 guidelines directed medical treatments. Of note, patients maintained a good adherence to the 157 prescribed treatments and to the non-pharmacological behavioral recommendations, such as control 158 of weight and vital parameters or water intake restriction, they had been taught during previous in-159 person visits at our HF clinic. 160

Our study shows an association of clinical characteristics, typically related with HF prognosis, 161

with a worse outcome also in a "virtual setting", given the higher rate of some of these variables in 162 red and yellow groups. In fact, for example, the need for high doses of loop diuretics has been 163 associated with unfavorable outcomes in patients with chronic HF 18-20 , and, in our study, it was 164 observed more frequently in higher risks groups. An association of loop diuretic dosage with adverse 165 outcomes was observed also in ESC HF Long Term Registry 21 . A recent meta-analysis highlighted 166 that high dose of loop diuretics are associated with increased adverse outcomes in chronic HF but 167 also concluded that prospective randomized studies are warranted to clarify whether these 168 associations indicate causality or high-dose diuretics are merely a marker of disease severity 22 , such 169 as suggested in a small prospective observational study 23 . 170

On the other hand, assessment of fluid overload and congestion is of crucial importance in the 171 management of HF, not only because of its correlation with prognosis 24-26 , but also for symptoms 172 relief. To assess the degree of congestion upon hospital discharge after HF exacerbation, published 173 scores incorporated different variables such as dyspnea, oedema, worsening of renal function or increased NT-proBNP 24-25 . However, few data are available on the evaluation of signs and symptoms 175 of congestion in the context of chronic HF. In a post-hoc analysis of the TIME-CHF study, some 176 clinical variables (e.g., oedema, dyspnea for mild exertion), which we included in our score, were 177 proven to be related with worse outcomes and congestion 26 . In light of the known prognostic value 178 of NT-proBNP and renal function assessment, as well as of their variations, to guide diuretic therapy 179 management we have also tried to exploit these laboratory data 24-28 . In low-risk patients we found 180 lower levels of NT-proBNP, a more preserved renal function and a lower rate of other clinical 181 characteristics known to be associated with worse outcomes. Nevertheless, by combining and 182 incorporating these data in our score, we believe we have been able to improve the remote 183 management and risk stratification of our HF patients by objectively identifying global clinical status 184 and its fluctuations during follow-up. 185

Nevertheless, at six months we observed in our study population a high rate of the composite 186 outcome of CV death and/or HF hospitalization which occurred in nearly one fifth of our study 187 population. The main finding of our study is that our score was able to correctly identify a low-risk 188 group, patients coded as green, with a significantly lower incidence of the composite endpoint 189 compared to the other two higher risk, yellow and red groups. Interestingly, the ability of 190

TeleHFCovid19-Score to correctly stratify the risk of adverse events in our patients was evident at 191 one month and was maintained up to six months follow-up where the incidence of the composite 192 outcome was still very low (9%) in the green group compared to 33% and 69% of the yellow and red 193 groups, respectively. Moreover, the cut-off score identified by the ROC analysis as having the highest 194 sensitivity and specificity to identify low-risk patients was 4.5, both at short-and at medium-term, 195 which is quite close to the cut-off of <4 that we had arbitrarily chosen to assign patients to the green In fact, while telemonitoring in several studies failed to impact prognosis, virtual visits and structured 204 telephone interviews have shown to improve quality of life and reduce the rate of re-hospitalizations 1-205 7 . In the DIAL trial patients who received the telephone intervention were less likely to be admitted 206 for worsening HF or to die and showed a better quality of life compared to those in the usual care 207 group 2 . 208 Therefore, we believe that in a post-pandemic era, the TeleHFCovid19-Score, and relative 209 questionnaire, could be used to manage chronic HF patients. For example, it could be applied to 210 remotely confirm patients' stability (e.g., patients in New York Heart Association class I or II at the 211 previous clinical evaluation) or to assess the effects of medical therapy optimization (e.g., guidelines 212 directed medical treatments dose adjustments and/or diuretic treatment reduction or withdrawal). 213

Consequently, it will be possible to ease the clinical care burden of HF management, allowing 214 physicians to focus on unstable patients who will benefit from in person visits. 215

Some limitations of the present study are to be acknowledged. First, the substantially limited 216 sample size and the selective nature of the study population (older HF patients, with a high prevalence 217 of HF with preserved ejection fraction and comorbidities), which may limit the generalizability of 218 results. Second, the absences of a control group, not feasible in an emergency situation, like COVID-219 19 pandemic. 220

The TeleHFCovid19-Score represents one of the few examples of risk stratification for the remote 223 management of HF patients developed during SARS-CoV-2 pandemic. The questionnaire, from 224 whom the score was derived, was easily and quickly administered to patients and/or their caregivers, 225 providing physicians with a tool able to standardize remote controls. Moreover, the TeleHFCovid19-226

Score showed a high sensibility and specificity to identify patients at a low risk of adverse events (HF 227 hospitalization and/or CV death). Given the high prevalence of chronic HF and the commitment 228 required for its management, strategies should be studied and implemented to appropriately utilize 229 clinical resources by directing efforts were most needed. Therefore, the TeleHFCovid19-Score may 230 identify accurately those chronic HF patients who, being at a low-risk of events, may be managed 231 safely in remote, thereby reserving tighter on-site clinical evaluations to higher risk patients which, 232

indeed, require more frequent FU. Furthermore, we believe that low-risk patients categorized as green 233 by the TeleHFCovid19-Score could be managed by specialized HF nurses with a standardized FU in 234 the context of a multidisciplinary HF clinic. 235

Anyway, the effectiveness of this tool in a post-pandemic word should be evaluated in a randomized 236 clinical trial which could verify the effects of our questionnaire and relative TeleHFCovid19-Score in 237 the management of HF patients. 238

Authors have no disclosure to declare. In panel a, b and c a comparison of primary (CV death and/or HF hospitalization) and secondary (CV 336 death and HF hospitalization singularly) outcomes between the three-color groups was respectively 337

shown with the trend at one, three and six months. 338 339 Figure 3 . ROC analysis of TeleHFCovid19-Score. 340

TeleHFCovid19-Score showed a good diagnostic power with a wide AUC, demonstrating a high 341 capacity of predicting primary outcome at short-and medium-terms. Patients with the lowest risk of 342 primary outcome were those with a score < 4.5 at all three follow-up intervals. 

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