Long-term outcomes in patients after COVID-19: data from the TARGET-VIP registry

Aim. To assess long-term outcomes within 12 months after hospital treatment of patients with coronavirus disease 2019 (COVID-19) as part of a prospective registry.Material and methods. Outcomes in the posthospital period were assessed in 827 patients diagnosed with COVID-19 (age, 58,0±14,8 years; men, 51,3%). For periods of 30-60 days, 6 and 12 months after discharge from the hospital, cases of death, nonfatal myocardial infarction (MI) and stroke, hospitalization, acute respiratory viral infections/influenza were assessed. The follow-up period was 13,0±1,5 months.Results. During the follow-up period, 35 (4,2%) patients died, 6 (0,73%) and 4 (0,48%) cases of MI and stroke were registered. In addition, 142 (17%) patients were hospitalized, while 217 (26,2%) patients had acute respiratory viral infections/ influenza. Factors of age and length of intensive care unit stay were significantly associated (p<0,001) with the risk of all-cause death (hazard ratio (HR)=1,085 per 1 year of life and HR=6,98, respectively), with the risk of composite endpoint (death, non-fatal MI and stroke): HR=1,081 per 1 year of life and HP=4,47. Of the 35 deaths, 11 (31%) were within the first 30 days of follow-up, and 19 (54%) — 90 days after discharge from the hospital. A higher probability of hospitalization was associated with older age (odds ratio (OR)=1,038; p<0,001), while a higher probability of acute respiratory viral infections/influenza was associated with younger age (OR=0,976 per 1 year of life; p<0,001) and female sex (OR=1,414; p=0,03).Conclusion. A prospective follow-up of 827 patients in the TARGET-VIP registry revealed that 12-month mortality was 4,2%, while more than half of the deaths (54%) were registered in the first 90 days, including 31% — for the first month after discharge from the hospital. The most common events were hospitalizations (17,0%) and acute respiratory viral infections/influenza (26,2%), while the rarest were myocardial infarction (0,73%) and stroke (0,48%). The key factors associated with 12-month mortality in the post-COVID-19 period were older age and intensive care unit stay during the reference hospitalization. A higher readmission rate during the follow-up period was associated with older age, and the prevalence of acute respiratory viral infections /influenza during the follow-up period was associated with younger patients and female sex

Clinical and Anamnestic Characteristics, Cardiovascular Pharmacotherapy and Long-term Outcomes in Multimorbid Patients after COVID-19

Aim. To study the clinical and anamnestic characteristics, pharmacotherapy of cardiovascular diseases (CVD) and long-term outcomes in post-COVID-19 patients with cardiovascular multimorbidity (CVMM), enrolled in the prospective hospital registry.Material and methods. In patients with confirmed COVID-19 included in the TARGET-VIP registry, the CVMM criterion was the presence of two or more CVDs: arterial hypertension (AH), coronary heart disease (CHD), chronic heart failure (CHF), atrial fibrillation (AF). There were 163 patients in the CVMM group and 382 – in the group without CVD. The information was obtained initially from hospital history sheet, and afterwards – from a telephone survey of patients after 30-60 days, 6 and 12 months, from electronic databases. The follow-up period was 13.0±1.5 months.Results. The age of post-COVID patients with CVMM was 73.7±9.6 years, without CVD – 49.4±12.4 years (p<0.001), the proportion of men was 53.9% and 58.4% (p=0.34). In the group with CVMM the majority of patients had AH (92.3-93.3%), CHD (90.4-91.4%), and minority – CHF (42.7-46.0%) and AF (42.9-43.4%). The combination of 3-4 CVDs prevailed (58.9-60.3%). The proportion of cases of chronic non-cardiac pathologies was higher in the CVMM group (80.9%) compared to the group without CVD (36.7%; p<0.001). The frequency of proper cardiovascular pharmacotherapy during the follow-up period decreased from 56.8% to 51.3% (p for trend = 0.18). The frequency of anticoagulant therapy in AF decreased significantly: from 89.1% at the discharge from the hospital to 56.4% after 30-60 days (p=0.001), 57.1% and 53.6% after 6 and 12 months of monitoring (p for a trend <0.001). There were no other significant changes in the frequency of other kinds of the proper cardiovascular pharmacotherapy (p>0.05). There were higher rate of all-cause mortality among patients with CMMM (12.9% vs 2.9%, p<0.001) as well as rates of hospitalization (34.7% and 9.9%, p<0.001) and non-fatal myocardial infarction (MI) – 2.5% vs 0.5% (p=0.048). The proportion of new cases of CVD in the groups with CVMM and without CVD was 5.5% and 3.7% (p=0.33). The incidence of acute respiratory viral infection (ARVI)/influenza was higher in the group without CVD – 28.3% vs 19.0% (p=0.02). The proportion of cases of recurrent COVID-19 in groups with CVMM and without CVD was 3.7 % and 1.8% (p=0.19).Conclusion. Post COVID-19 patients with CVMM were older and had the bigger number of chronic non-cardiac diseases than patients without CVD. The quality of cardiovascular pharmacotherapy in patients with CVMM was insufficient at the discharge from the hospital with following non-significant decrease during 12 months of follow-up. The frequency of anticoagulant therapy in AF decreased by 1.6 times after 30-60 days and by 1.7 times during the year of follow-up. The proportion of new cases of CVD was 5.5% and 3.7% with no significant differences between compared groups. The rate of all-cause mortality, hospitalizations and non-fatal MI was significantly higher in patients with CVMM, but the frequency of ARVI/influenza was significantly higher in patients without CVD. Recurrent COVID-19 was registered in 3.7% and 1.8% of cases, there were no significant differences between compared groups

Prehospital Period in Patients with COVID-19: Cardiovascular Comorbidity and Pharmacotherapy During the First Epidemic Wave (Hospital Registry Data)

Aim. Based on the data from the register of patients with COVID-19 and community-acquired pneumonia (CAP), analyze the duration of the prehospital period, cardiovascular comorbidity and the quality of prehospital pharmacotherapy of concomitant cardiovascular diseases (CVD).Material and methods. Patients were included to the study which admitted to the FSBI "NMHC named after N.I. Pirogov" of the Ministry of Health of the Russian Federation with a suspected or confirmed diagnosis of COVID-19 and/or CAP. The data for prehospital therapy, information from medical histories and a patients’survey in the hospital or by telephone contact 1-2 weeks after discharge were study. The duration of the prehospital stage was determined from the date of the appearance of clinical symptoms of coronavirus infection to the date of hospitalization.Results. The average age of the patients (n=1130; 579 [51.2%] men and 551 [48.8%] women) was 57.5±12.8 years. The prehospital stage was 7 (5,0; 10,0) days and did not differ significantly in patients with the presence and absence of CVD, but was significantly less in the deceased than in the surviving patients, as well as in those who required artificial lung ventilation (ALV). 583 (51.6%) patients had at least one CVD. Cardiovascular comorbidity was registered in 222 (42.7%) patients with hypertension, 210 (95.5%) patients with coronary heart disease (CHD), 104 (91.2%) patients with atrial fibrillation (AF). The inclusion of non-cardiac chronic diseases in the analysis led to an increase in the total proportion of patients with concomitant diseases to 65.8%. Approximately a quarter of hypertensive patients did not receive antihypertensive therapy, a low proportion of patients receiving antiplatelet agents and statins for CHD was revealed – 53% and 31.8%, respectively, anticoagulants for AF – 50.9%.Conclusion. The period from the onset of symptoms to hospitalization was significantly shorter in the deceased than in the surviving patients, as well as in those who required ALV. The proportion of people with a history of at least one CVD was about half of the entire cohort of patients. In patients with CVD before COVID-19 disease, a low frequencies of prescribing antihypertensive drugs, statins, antiplatelet agents and anticoagulants (in patients with AF) were recorded at the prehospital stage

Combination of Atrial Fibrillation and Coronary Heart Disease in Patients in Clinical Practice: Comorbidities, Pharmacotherapy and Outcomes (Data from the REСVASA Registries)

Aim. Assess the structure of comorbid conditions, cardiovascular pharmacotherapy and outcomes in patients with atrial fibrillation (AF) and concomitant coronary artery disease (CAD) included in the outpatient and hospital RECVASA registries.Materials and methods. 3169 patients with AF were enrolled in outpatient RECVASA (Ryazan), RECVASA AF-Yaroslavl registries and hospital RECVASA AF (Moscow, Kursk, Tula). 2497 (78.8%) registries of patients with AF had CAD and 703 (28.2%) of them had a previous myocardial infarction (MI).Results. There were 2,497 patients with a combination of AF and CAD (age was 72.2±9.9 years; 43.1% of men; CHA2DS2-VASc – 4.57±1.61 points; HAS-BLED – 1.60±0,75 points), and the group with AF without CAD included 672 patients (age was 66.0±12.3 years; 43.2% of men; CHA2DS2-VASc – 3.26±1.67 points; HAS-BLED – 1,11±0.74 points). Patients with CAD were on average 6.2 years older and had a higher risk of thromboembolic and hemorrhagic complications (p<0.05). 703 patients with a combination of AF and CAD had the previous myocardial infarction (MI; age was 72.3±9.5 years; 55.2% of men; CHA2DS2-VASc – 4.57±1.61; HAS-BLED – 1.65±0.76), and 1794 patients didn't have previous MI (age was 72.2±10.0 years; 38.4% of men; CHA2DS2-VASc – 4.30±1.50; HAS-BLED – 1.58±0.78). The proportion of men was 1.4 times higher among those with the previous MI. Patients with a combination of AF and CAD significantly more often (p <0.0001) than in the absence of CAD received a diagnosis of hypertension (93.8% and 78.6%), chronic heart failure (90.1% and 51.2%), diabetes mellitus (21.4% and 13.8%), chronic kidney disease (24.8% and 17.7%), as well as anemia (7.0% and 3.0%; p=0.001). Patients with and without the previous MI had the only significant difference in the form of a diabetes mellitus higher incidence having the previous MI (27% versus 19.2%, p=0.0008). The frequency of proper cardiovascular pharmacotherapy was insufficient, mainly in the presence of CAD (67.8%) than in its absence (74.5%), especially the prescription of anticoagulants (39.1% and 66.2%; p <0.0001), as well as in the presence of the previous MI (63.3%) than in its absence (74.3%). The presence of CAD and, in particular, the previous MI, was significantly associated with a higher risk of death (risk ratio [RR]=1.58; 95% confidence interval [CI] was 1.33-1.88; p <0.001 and RR=1.59; 95% CI was 1.33-1.90; p <0.001), as well as with a higher risk of developing a combined cardiovascular endpoint (RR=1.88; 95% CI was 1.17-3 , 00; p <0.001 and RR=1.75; 95% CI was 1.44-2.12; p<0.001, respectively).Conclusion. 78.8% of patients from AF registries in 5 regions of Russia were diagnosed with CAD, of which 28.2% had previously suffered myocardial infarction. Patients with a combination of AF and CAD more often than in the absence of CAD had hypertension, chronic heart failure, diabetes, chronic kidney disease and anemia. Patients with the previous MI had higher incidence of diabetes than those without the previous MI. The frequency of proper cardiovascular pharmacotherapy was insufficient, and to a greater extent in the presence of CAD and the previous MI than in their absence. All-cause mortality was recorded in patients with a combination of AF and CAD more often than in the absence of CAD. All-cause mortality and the incidence of nonfatal myocardial infarction were higher in patients with AF and the previous MI than in those without the previous MI. The presence of CAD and, in particular, the previous MI, was significantly associated with a higher risk of death, as well as a higher risk of developing a combined cardiovascular endpoint

Patients with a Combination of Atrial Fibrillation and Chronic Heart Failure in Clinical Practice: Comorbidities, Drug Treatment and Outcomes

Aim. To assess in clinical practice the structure of multimorbidity, cardiovascular pharmacotherapy and outcomes in patients with a combination of atrial fibrillation (AF) and chronic heart failure (CHF) based on prospective registries of patients with cardiovascular diseases (CVD).Materials and Methods. The data of 3795 patients with atrial fibrillation (AF) were analyzed within the registries RECVASA (Ryazan), RECVASA FP (Moscow, Kursk, Tula, Yaroslavl), REGION-PO and REGION-LD (Ryazan), REGION-Moscow, REGATA (Ryazan). The comparison groups consisted of 3016 (79.5%) patients with AF in combination with CHF and 779 (29.5%) patients with AF without CHF. The duration of prospective observation is from 2 to 6 years.Results. Patients with a combination of AF and CHF (n=3016, age was 72.0±10.3 years; 41.8% of men) compared with patients with AF without CHF (n=779, age was 70.3±12.0 years; 43.5% of men) had a higher risk of thromboembolic complications (CHA2DS2-VASc – 4.68±1.59 and 3.10±1.50; p<0.001) and hemorrhagic complications (HAS-BLED – 1.59±0.77 and 1.33±0.76; p<0.05). Patients with a combination of AF and CHF significantly more often (p<0.001) than in the absence of CHF were diagnosed with arterial hypertension (93.9% and 83.8%), coronary heart disease (87.9% and 53,5%), myocardial infarction (28.4% and 14.0%), diabetes mellitus (22.4% and 7.7%), chronic kidney disease (24.8% and 16.2%), as well as respiratory diseases (20.1% and 15.3%; p=0.002). Patients with AF in the presence of CHF, compared with patients without CHF, were more often diagnosed with a permanent form of arrhythmia (49.3% and 32.9%; p<0.001) and less often paroxysmal (22.5% and 46.2%; p<0.001) form  of  arrhythmia.  Ejection  fraction  ≤40%  (9.3%  and  1.2%;  p<0.001),  heart  rate  ≥90/min  (23.7% and 19.3%; p=0.008) and blood pressure ≥140/90 mm Hg (59.9% and 52.2%; p<0.001) were recorded with AF in the presence of CHF more often than in the absence of CHF. The frequency of proper cardiovascular pharmacotherapy was higher, albeit insufficient, in the presence of CHF (64.9%) than in the absence of it (56.1%), but anticoagulants were prescribed less frequently when AF and CHF were combined (38.8% and  49, 0%; p<0.001). The frequency of unreasonable prescription of antiplatelet agents instead of anticoagulants was 52.5% and 33.3% (p<0.001) in the combination of AF, CHF and coronary heart disease, as well as in the combination of AF with coronary heart disease but without CHF. Patients with AF and CHF during the observation period compared with those without CHF had higher mortality from all causes (37.6% and 30.3%; p=0.001), the frequency of non-fatal cerebral stroke (8.2% and 5.4%; p=0.032) and myocardial infarction (4.7% and 2.5%; p=0.036), hospitalizations for CVD (22.8% and 15.5%; p<0.001).Conclusion. Patients with a combination of AF and CHF, compared with the group of patients with AF without CHF, were older, had a higher risk of thromboembolic and hemorrhagic complications, they were more often diagnosed with other concomitant cardiovascular and chronic noncardiac diseases, decreased left ventricular ejection fraction, tachysystole, failure to achieve the target blood pressure level in the presence of arterial hypertension. The frequency of prescribing proper cardiovascular pharmacotherapy was higher, albeit insufficient, in the presence of CHF, while the frequency of prescribing anticoagulants was less. The  incidence of mortality from all causes, the development of non-fatal myocardial infarction   and cerebral stroke, as well as the incidence of hospitalizations for CVDs were higher in AF associated with CHF

Patients with Premature Cardiovascular Diseases in Ambulatory Practice: Demographic Characteristics, Risk Factors and Adherence to the Medical Therapy (Data of RECVASA Registry)

Aim. To evaluate the gender characteristics, educational level, cardiovascular diseases (CVD) risk factors and adherence to drug treatment in patients with premature CVD in an outpatient prospective registerу.   Material and methods. 3690 patients with hypertension, coronary artery disease, chronic heart failure, atrial fibrillation and their combinations were enrolled in the RECVASA registry in Ryazan region of Russia. Groups of patients with early development of CVD (criterion 1 – the age of 18-49 years old, criterion 2 – the age of men 18-54 years old and women – 18-64 years old) were compared with the corresponding older groups. The gender characteristics, educational level, CVD risk factors, and adherence to drug treatment were analyzed.   Results. According to criterion 1, the age groups of 18-49 years old and ≥50 years old included 347 (9.4%) and 3343 (90.6%) patients, respectively, 144 (41.5%) and 902 (27, 0%), respectively were   men, p<0.0001. According to criterion 2, 1369 (37.1%) patients were assigned to the group with early development of CVD, of which 254 (18.6%) were men under 55 and 1115 (81.4%) were women under 65. The group of older patients included 2321 individuals, of which 792 were men (34.1%) and 1529 were women (65.9%). According to criterion 2, the proportion of men in the group of patients with early development of CVD, was 2.2 times lower, than in the older age group (18.6% vs 41.5%, respectively; p<0.0001). Patients <50 years old were more likely to have higher education, than the group of patients ≥50 years old (42.3 vs 25.9%; p<0.0001), including among both men and women. According to criterion 2, the same statistically significant differences were observed (36.2 vs 21.3%; p<0.0001), including among both men and women. The proportion of smokers was 2 times higher in patients younger than 50 years old, than in patients ≥50 years old (44.0 vs 21.7%; p<0.0001). The largest proportion of smokers was among men and women <50 years old (69.4% and 24.1%, respectively). According to criterion 1, hypercholesterolemia (>5 mmol/L) was diagnosed significantly less frequently in patients with early development of CVD than in the older age group (47.8 vs 54.6%; p=0.047); these differences were obtained due to women (46.9 vs 58.8%; p=0.008), the proportion of individuals with hypercholesterolemia did not significantly differ among men. According to criterion 2, statistically significant differences in the frequency of hypercholesterolemia were not detected among both men and women. There was no differences in the incidence of family history (FH) of premature CVD in the study groups, while the proportion of patients with FH of premature CVD was significantly higher in men <55 years old than in women <65 years old (44.8 vs 37.7%; p<0.0001). According to criterion 1 the proportion of patients with low adherence to treatment was higher in patients with early development of CVD than in the older age group (57.1% vs 46.1%; p=0.0006), the proportion of patients with high adherence was 22.9% and 32.4% (p=0.0013), respectively. According to criterion 2, there were no differences in adherence to treatment.   Conclusions. According to RECVASA registry, patients with early development of CVD were more likely to be men, in accordance with criterion 1. Patients with early development of CVD, including men and women, according to both criteria, were characterized by a significantly higher proportion of individuals with higher education and a higher proportion of smokers. In patients with early development of CVD using criterion 1, in contrast to criterion 2, hypercholesterolemia was diagnosed significantly less often than in the older age group. It is preferable to use criterion 1 to assess hypercholesterolemia in patients with early development of CVD. The proportion of individuals with FH of premature CVD was significantly higher in men <55 years old than in women <65 years old. Patients with early development of CVD according to criterion 1 were characterized by a lower adherence to drug treatment. Individuals with early development of CVD, especially <50 years old are the target group for comprehensive prevention, not only due to improving the quality of proven effective drug therapy, but also by correcting risk factors and increasing level of adherence to treatment

Early cardiovascular multimorbidity in out- and in-patient care: age characteristics and medication therapy (data from the REKVAZA and REKVAZA-CLINIC registries)

Aim. To assess the age and sex characteristics, comorbidities and medication therapy in patients with early cardiovascular multimorbidity in out- and in-patient care.Material and methods. The REKVAZA registry includes 3,690 patients with hypertension (HTN), coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF) and their combinations, who applied to primary care facilities in Ryazan in 2012-2013. The hospital registry REKVAZA-CLINIC included 17,018 patients hospitalized due to cardiovascular disease (CVD) at the National Medical Research Center for Therapy and Preventive Medicine from April 2013 to March 2020. The groups of patients with early cardiovascular multimorbidity were compared according to two criteria: criterion 1 — age 18-49 years; criterion 2 — the age of men, 18-54 years; women, 18-64 years. The structure of CVD and related diseases, as well as cardiovascular therapy were analyzed.Results. The proportion of persons with early cardiovascular multimorbidity from the total number of patients with cardiovascular multimorbidity was as follows: using criterion 1 — 4,9% (145/2959) and 4,94% (571/11557) (p=0,66), criterion 2 — 29,0% (859/ 2959) and 18,8% (2168/11557) (p<0,0001), respectively. Using criterion 2, in contrast to criterion 1, the proportion of men with early multimorbidity was 2,7 times less in the REKVAZA registry (17,1 vs 45,5%; p<0,0001) and 1,8 times less in the REKVAZA-CLINIC registry (44,2 vs 80,9%; p<0,0001). Among individuals with >2 CVDs (HTN, CAD, HF, AF, myocardial infarction, acute cerebrovascular accident), the proportion of individuals with early development of each of the listed diseases was significantly higher in the out- and in-patient registries, when using criterion 2 (14-29%) compared to criterion 1 (2-2,5%). Among patients with early onset of CVD in the outpatient registry, when criteria 1 and 2 were used, the proportion of patients with cardiovascular multimorbidity was 41,8 and 62,7% (p<0,0001), respectively; in the inpatient registry — 34,1 and 45,5% (p<0,0001). That is, at the age of <50 years> 1/3 of patients were found to have combined CVDs. Using criterion 2, compared with criterion 1, the proportion of persons with HTN and concomitant CVD among all patients with early HTN was 1,5 times higher (62,8 vs 41,6%; p<0,0001) in the outpatient register and 1,3 times higher in the inpatient one (48,9 vs 37,5%; p<0,0001). The proportions of persons with HTN in combination with other CVDs were among all hypertensive patients aged <45 and <40 years: in the outpatient registry, 35,5% (61/172) and 33,3% (38/114) cases, respectively, and in the inpatient — 27,8% (215/772) and 26,5% (95/359), respectively. According to the data of both out- and inpatient registries, in patients with early development of HTN (<50 years of age) and concomitant CVDs, compared with those without such a combination, there was a greater number of noncardiac diseases (18,3 vs 7,0%; p=0,001), diabetes (12,9 vs 4,7%; p<0,0001), respectively. In the inpatient registry, in addition to diabetes, there was a greater proportion of people with gastrointestinal diseases (78,7 vs 73,2%; p=0,02) and obesity (37,9 vs 30,3%; p=0,004). Among patients <50 years of age, the prevalence of those taking appropriate medications was higher than in the group of patients meeting criterion 2 — 68,0% vs 63,2%, respectively (p=0,03).Conclusion. Early cardiovascular multimorbidity in the REKVAZA and REKVAZA-CLINIC registries was detected in 14-29% of the total number of combined CVD cases when using criterion 2 and only in 2-5% when using criterion 1. However, in relation to the total number of patients with early CVD development, individuals with cardiovascular multimorbidity make up the majority. It is preferable to use age <50 years as a criterion for early cardiovascular multimorbidity. But the criterion for the early development of HTN combined with other CVDs is appropriate to consider the age <40 years. Persons with early cardiovascular multimorbidity, especially at the age of 18-49 years, are the target group for the implementation of preventive measures

²¹²Pb: Production Approaches and Targeted Therapy Applications

Over the last decade, targeted alpha therapy has demonstrated its high effectiveness in treating various oncological diseases. Lead-212, with a convenient half-life of 10.64 h, and daughter alpha-emitter short-lived 212Bi (T1/2 = 1 h), provides the possibility for the synthesis and purification of complex radiopharmaceuticals with minimum loss of radioactivity during preparation. As a benefit for clinical implementation, it can be milked from a radionuclide generator in different ways. The main approaches applied for these purposes are considered and described in this review, including chromatographic, solution, and other techniques to isolate 212Pb from its parent radionuclide. Furthermore, molecules used for lead’s binding and radiochemical features of preparation and stability of compounds labeled with 212Pb are discussed. The results of preclinical studies with an estimation of therapeutic and tolerant doses as well as recently initiated clinical trials of targeted radiopharmaceuticals are presented