Showing papers in "JAMA Cardiology in 2020"

Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China.

Abstract: Importance Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited. Objective To explore the association between cardiac injury and mortality in patients with COVID-19. Design, Setting, and Participants This cohort study was conducted from January 20, 2020, to February 10, 2020, in a single center at Renmin Hospital of Wuhan University, Wuhan, China; the final date of follow-up was February 15, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study. Main Outcomes and Measures Clinical laboratory, radiological, and treatment data were collected and analyzed. Outcomes of patients with and without cardiac injury were compared. The association between cardiac injury and mortality was analyzed. Results A total of 416 hospitalized patients with COVID-19 were included in the final analysis; the median age was 64 years (range, 21-95 years), and 211 (50.7%) were female. Common symptoms included fever (334 patients [80.3%]), cough (144 [34.6%]), and shortness of breath (117 [28.1%]). A total of 82 patients (19.7%) had cardiac injury, and compared with patients without cardiac injury, these patients were older (median [range] age, 74 [34-95] vs 60 [21-90] years;P Conclusions and Relevance Cardiac injury is a common condition among hospitalized patients with COVID-19 in Wuhan, China, and it is associated with higher risk of in-hospital mortality.

Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19).

Abstract: Importance Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents. Information regarding the impact of cardiovascular complication on fatal outcome is scarce. Objective To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19. Design, Setting, and Participants This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020. Analysis began February 25, 2020. Main Outcomes and Measures Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels. Result Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died. The mean (SD) age was 58.50 (14.66) years. Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels. The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs. Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]). Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530,P Conclusions and Relevance Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable. Myocardial injury is associated with cardiac dysfunction and arrhythmias. Inflammation may be a potential mechanism for myocardial injury. Aggressive treatment may be considered for patients at high risk of myocardial injury.

Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19).

Abstract: Importance Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown. Objective To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness. Design, Setting, and Participants In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020. Exposure Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription–polymerase chain reaction on swab test of the upper respiratory tract. Main Outcomes and Measures Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained. Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor–matched patients (n = 57). Results Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years. The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days. Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization. At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%). Compared with healthy controls and risk factor–matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2. A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22). There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms;P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL;P = .002) but not for native T2 mapping. None of these measures were correlated with time from COVID-19 diagnosis (native T1:r = 0.07;P = .47; native T2:r = 0.14;P = .15; hsTnT:r = −0.07;P = .50). High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33;P Conclusions and Relevance In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19).

Abstract: Importance Virus infection has been widely described as one of the most common causes of myocarditis. However, less is known about the cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective To describe the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from the influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms. Design, Setting, and Participant This case report describes an otherwise healthy 53-year-old woman who tested positive for COVID-19 and was admitted to the cardiac care unit in March 2020 for acute myopericarditis with systolic dysfunction, confirmed on cardiac magnetic resonance imaging, the week after onset of fever and dry cough due to COVID-19. The patient did not show any respiratory involvement during the clinical course. Exposure Cardiac involvement with COVID-19. Main Outcomes and Measures Detection of cardiac involvement with an increase in levels of N-terminal pro–brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, echocardiography changes, and diffuse biventricular myocardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging. Results An otherwise healthy 53-year-old white woman presented to the emergency department with severe fatigue. She described fever and dry cough the week before. She was afebrile but hypotensive; electrocardiography showed diffuse ST elevation, and elevated high-sensitivity troponin T and NT-proBNP levels were detected. Findings on chest radiography were normal. There was no evidence of obstructive coronary disease on coronary angiography. Based on the COVID-19 outbreak, a nasopharyngeal swab was performed, with a positive result for SARS-CoV-2 on real-time reverse transcriptase–polymerase chain reaction assay. Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis. She was treated with dobutamine, antiviral drugs (lopinavir/ritonavir), steroids, chloroquine, and medical treatment for heart failure, with progressive clinical and instrumental stabilization. Conclusions and Relevance This case highlights cardiac involvement as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia.

Potential Effects of Coronaviruses on the Cardiovascular System: A Review.

Abstract: Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19) has reached a pandemic level. Coronaviruses are known to affect the cardiovascular system. We review the basics of coronaviruses, with a focus on COVID-19, along with their effects on the cardiovascular system. Observations Coronavirus disease 2019 can cause a viral pneumonia with additional extrapulmonary manifestations and complications. A large proportion of patients have underlying cardiovascular disease and/or cardiac risk factors. Factors associated with mortality include male sex, advanced age, and presence of comorbidities including hypertension, diabetes mellitus, cardiovascular diseases, and cerebrovascular diseases. Acute cardiac injury determined by elevated high-sensitivity troponin levels is commonly observed in severe cases and is strongly associated with mortality. Acute respiratory distress syndrome is also strongly associated with mortality. Conclusions and Relevance Coronavirus disease 2019 is associated with a high inflammatory burden that can induce vascular inflammation, myocarditis, and cardiac arrhythmias. Extensive efforts are underway to find specific vaccines and antivirals against SARS-CoV-2. Meanwhile, cardiovascular risk factors and conditions should be judiciously controlled per evidence-based guidelines.

Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases.

Abstract: Importance Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be documented in various tissues, but the frequency of cardiac involvement as well as possible consequences are unknown. Objective To evaluate the presence of SARS-CoV-2 in the myocardial tissue from autopsy cases and to document a possible cardiac response to that infection. Design, Setting, and Participants This cohort study used data from consecutive autopsy cases from Germany between April 8 and April 18, 2020. All patients had tested positive for SARS-CoV-2 in pharyngeal swab tests. Exposures Patients who died of coronavirus disease 2019. Main Outcomes and Measures Incidence of SARS-CoV-2 positivity in cardiac tissue as well as CD3+, CD45+, and CD68+cells in the myocardium and gene expression of tumor necrosis growth factor α, interferon γ, chemokine ligand 5, as well as interleukin-6, -8, and -18. Results Cardiac tissue from 39 consecutive autopsy cases were included. The median (interquartile range) age of patients was 85 (78-89) years, and 23 (59.0%) were women. SARS-CoV-2 could be documented in 24 of 39 patients (61.5%). Viral load above 1000 copies per μg RNA could be documented in 16 of 39 patients (41.0%). A cytokine response panel consisting of 6 proinflammatory genes was increased in those 16 patients compared with 15 patients without any SARS-CoV-2 in the heart. Comparison of 15 patients without cardiac infection with 16 patients with more than 1000 copies revealed no inflammatory cell infiltrates or differences in leukocyte numbers per high power field. Conclusions and Relevance In this analysis of autopsy cases, viral presence within the myocardium could be documented. While a response to this infection could be reported in cases with higher virus load vs no virus infection, this was not associated with an influx of inflammatory cells. Future investigations should focus on evaluating the long-term consequences of this cardiac involvement.

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).

Abstract: Importance Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)–associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. Objective To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. Design, Setting, and Participants This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. Main Outcomes and Measures Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. Results Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds;P Conclusions and Relevance In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.

Association of Coronavirus Disease 2019 (COVID-19) With Myocardial Injury and Mortality.

Abstract: Coronavirus disease 2019 (COVID-19) has emerged as a pandemic and a public health crisis of global proportions. As a medical community, we are actively engaged in a real-time data gathering mode to facilitate active learning and an expedited study of best practices of care. Although we are becoming more aware of the natural history of COVID-19, we have had scant information as of yet that addresses any unique risks of COVID-19 for those with underlying cardiovascular disease. Such information is of paramount importance as we now must begin to consider the potential for direct and indirect adverse effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the heart and especially so in those with already established heart disease. The statistics to date are staggering and relentlessly mounting. As of March 25, 2020, there have been more than 430 000 individuals in more than 170 countries with confirmed COVID19, of whom more than 19 000 have died. In the US, there have been more than 49 000 confirmed cases of COVID-19 in all 50 states and Washington, DC. It is clear that the number of infections in the US, the number needing critical care interventions, and especially the numbers of deaths will continue to escalate. The available data from China and Italy as well as the early experience in the US indicate that COVID-19 is a relatively mild condition in most affected individuals, but in others, it can be very severe and deadly. What we now know is that individuals at greatest risk of serious illness sufficient to require intensive care and those at greatest risk of mortality are older individuals, particularly older individuals with underlying comorbid disease, including cardiovascular disease.1-5 However, severe disease requiring hospitalization and even deaths have been reported in younger adults. Patients with long-term coronary artery disease and those with risk factors for atherosclerotic cardiovascular disease have a heightened risk of developing an acute coronary syndrome during acute infections, which has been shown previously in epidemiologic and clinical studies of influenza6-8 and other acute inflammatory conditions.9 Such acute coronary events could result from the severe increase in myocardial demand triggered by infections that precipitate myocardial injury or infarction, akin to type 2 myocardial infarction. Alternatively, circulating cytokines released during a severe systemic inflammatory stress could lead to atherosclerotic plaque instability and rupture. Similarly, patients with heart failure are also prone to hemodynamic decompensation during the stress of severe infectious illnesses. Thus, it is anticipated that patients with underlying cardiovascular diseases, which are more prevalent in older adults, would be susceptible to higher risks of adverse outcomes and death during the severe and aggressive inflammatory responses to COVID-19 than individuals who are younger and healthier. In addition, acute/fulminant myocarditis as well as heart failure have been reported with Middle East respiratory syndrome coronavirus and could be expected to occur with SARS-CoV-2, given the similar pathogenicity. Two articles published in JAMA Cardiology from 2 academic hospitals in Wuhan, China, the epicenter of the COVID-19 pandemic,10,11 support these concepts while also providing novel insights into the incidence and consequences of myocardial injury associated with SARS-CoV-2. Shi et al10 present a cohort study of 416 hospitalized patients with COVID-19 confirmed by reverse transcriptase–polymerase chain reaction, of whom 82 (19.7%) had evidence of myocardial injury manifested by elevation of high-sensitivity troponin I (TnI) levels. Patients with myocardial injury had a significantly higher inhospital mortality rate (42 of 82 [51.2%]) compared with those without myocardial injury (15 of 335 [4.5%]), and among those with myocardial injury, greater degrees of TnI elevation were associated with higher mortality rates. Similar observations were reported by Guo et al11 in 187 patients hospitalized with laboratory-confirmed COVID-19, of whom 52 (27.8%) had myocardial injury as determined by elevated levels of troponin T (TnT). In-hospital mortality was 59.6% (31 of 52) in those with elevated TnT levels compared with 8.9% (12 of 135) in those with normal TnT levels. Of note, the highest mortality rates were observed in those with elevated TnT levels who had underlying cardiovascular disease (25 of 36 [69.4%]), but mortality rates were also considerable in those with elevated TnT levels without prior cardiovascular disease (6 of 16 [37.5%]). In contrast, patients with known cardiovascular disease without elevation of TnT levels had a relatively favorable but still worrisome prognosis (mortality of 13.3% [4 of 30]). Guo et al11 provide additional novel insights that TnT levels are significantly associated with levels of C-reactive protein and N-terminal pro-B-type natriuretic peptide (NT-proBNP), thus linking myocardial injury to severity of inflammation and ventricular dysfunction. Their data also show progressive serial increases in both TnT and NTproBNP levels during hospitalization in patients who follow a deteriorating clinical course toward death, whereas those with a more favorable outcome with less severe illness, successful Viewpoint

Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China.

Abstract: Importance Data are lacking whether patients with hypertension who are taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have increased severity or risk of mortality during hospitalization for coronavirus disease 2019 (COVID-19). Objective To investigate the association between ACEIs/ARBs and severity of illness and mortality in patients with hypertension hospitalized for COVID-19 infection. Design, Setting, and Participants Retrospective, single-center case series of the 1178 hospitalized patients with COVID-19 infections at the Central Hospital of Wuhan, China, from January 15 to March 15, 2020. Main Outcomes and Measures COVID-19 was confirmed by real-time reverse transcription–polymerase chain reaction and epidemiologic, clinical, radiologic, laboratory, and drug therapy data were analyzed in all patients. The percentage of patients with hypertension taking ACEIs/ARBs was compared between those with severe vs nonsevere illness and between survivors vs nonsurvivors. Results Of the 1178 patients with COVID-19, the median age was 55.5 years (interquartile range, 38-67 years) and 545 (46.3%) were men. The overall in-hospital mortality was 11.0%. There were 362 patients with hypertension (30.7% of the total group; median age, 66.0 years [interquartile range, 59-73 years]; 189 [52.2%] were men), of whom 115 (31.8%) were taking ACEI/ARBs. The in-hospital mortality in the patients with hypertension was 21.3%. The percentage of patients with hypertension taking ACEIs/ARBs did not differ between those with severe and nonsevere infections (32.9% vs 30.7%;P = .65) nor did it differ between nonsurvivors and survivors (27.3% vs 33.0%;P = .34). Similar findings were observed when data were analyzed for patients taking ACEIs and those taking ARBs. Conclusions and Relevance This study provides clinical data on the association between ACEIs/ARBs and outcomes in patients with hypertension hospitalized with COVID-19 infections, suggesting that ACEIs/ARBs are not associated with the severity or mortality of COVID-19 in such patients. These data support current guidelines and societal recommendations for treating hypertension during the COVID-19 pandemic.

Cardiovascular Magnetic Resonance Findings in Competitive Athletes Recovering From COVID-19 Infection.

Abstract: This study investigates the use of cardiac magnetic resonance imaging in competitive athletes who recovered from coronavirus disease 2019 (COVID-10) to detect myocardial inflammation that would identify high-risk athletes for return to competitive play.

Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19).

Abstract: Importance The role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the coronavirus disease 2019 (COVID-19) pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use. Objective To study the association between use of ACEIs/ARBs with the likelihood of testing positive for COVID-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of COVID-19 (eg, hospitalization, intensive care unit admission, and requirement for mechanical ventilation). Design, Setting, and Participants Retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. All patients tested for COVID-19 between March 8 and April 12, 2020, were included. Exposures History of taking ACEIs or ARBs at the time of COVID-19 testing. Main Outcomes and Measures Results of COVID-19 testing in the entire cohort, number of patients requiring hospitalizations, intensive care unit admissions, and mechanical ventilation among those who tested positive. Results A total of 18 472 patients tested for COVID-19. The mean (SD) age was 49 (21) years, 7384 (40%) were male, and 12 725 (69%) were white. Of 18 472 patients who underwent COVID-19 testing, 2285 (12.4%) were taking either ACEIs or ARBs. A positive COVID-19 test result was observed in 1735 of 18 472 patients (9.4%). Among patients who tested positive, 421 (24.3%) were admitted to the hospital, 161 (9.3%) were admitted to an intensive care unit, and 111 (6.4%) required mechanical ventilation. Overlap propensity score weighting showed no significant association of ACEI and/or ARB use with COVID-19 test positivity (overlap propensity score–weighted odds ratio, 0.97; 95% CI, 0.81-1.15). Conclusions and Relevance This study found no association between ACEI or ARB use and COVID-19 test positivity. These clinical data support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic. However, further study in larger numbers of hospitalized patients receiving ACEI and ARB therapy is needed to determine the association with clinical measures of COVID-19 severity.

Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit.

Abstract: This case series assesses QT intervals for French patients with coronavirus disease 2019 (COVID-19) treated with hydroxychloroquine alone or in combination with azithromycin.

Characteristics Associated With Out-of-Hospital Cardiac Arrests and Resuscitations During the Novel Coronavirus Disease 2019 Pandemic in New York City.

Abstract: Importance Risk factors for out-of-hospital death due to novel coronavirus disease 2019 (COVID-19) are poorly defined From March 1 to April 25, 2020, New York City, New York (NYC), reported 17 118 COVID-19–related deaths On April 6, 2020, out-of-hospital cardiac arrests peaked at 305 cases, nearly a 10-fold increase from the prior year Objective To describe the characteristics (race/ethnicity, comorbidities, and emergency medical services [EMS] response) associated with outpatient cardiac arrests and death during the COVID-19 pandemic in NYC Design, Setting, and Participants This population-based, cross-sectional study compared patients with out-of-hospital cardiac arrest receiving resuscitation by the NYC 911 EMS system from March 1 to April 25, 2020, compared with March 1 to April 25, 2019 The NYC 911 EMS system serves more than 84 million people Exposures The COVID-19 pandemic Main Outcomes and Measures Characteristics associated with out-of-hospital arrests and the outcomes of out-of-hospital cardiac arrests Results A total of 5325 patients were included in the main analysis (2935 men [562%]; mean [SD] age, 71 [18] years), 3989 in the COVID-19 period and 1336 in the comparison period The incidence of nontraumatic out-of-hospital cardiac arrests in those who underwent EMS resuscitation in 2020 was 3 times the incidence in 2019 (475/100 000 vs 159/100 000) Patients with out-of-hospital cardiac arrest during 2020 were older (mean [SD] age, 72 [18] vs 68 [19] years), less likely to be white (611 of 2992 [204%] vs 382 of 1161 [329%]), and more likely to have hypertension (2134 of 3989 [535%] vs 611 of 1336 [457%]), diabetes (1424 of 3989 [357%] vs 348 of 1336 [260%]), and physical limitations (2259 of 3989 [566%] vs 634 of 1336 [475%]) Compared with 2019, the odds of asystole increased in the COVID-19 period (odds ratio [OR], 350; 95% CI, 253-484;P Conclusions and Relevance In this population-based, cross-sectional study, out-of-hospital cardiac arrests and deaths during the COVID-19 pandemic significantly increased compared with the same period the previous year and were associated with older age, nonwhite race/ethnicity, hypertension, diabetes, physical limitations, and nonshockable presenting rhythms Identifying patients with the greatest risk for out-of-hospital cardiac arrest and death during the COVID-19 pandemic should allow for early, targeted interventions in the outpatient setting that could lead to reductions in out-of-hospital deaths

A New Equation for Calculation of Low-Density Lipoprotein Cholesterol in Patients With Normolipidemia and/or Hypertriglyceridemia

Abstract: Importance Low-density lipoprotein cholesterol (LDL-C), a key cardiovascular disease marker, is often estimated by the Friedewald or Martin equation, but calculating LDL-C is less accurate in patients with a low LDL-C level or hypertriglyceridemia (triglyceride [TG] levels ≥400 mg/dL). Objective To design a more accurate LDL-C equation for patients with a low LDL-C level and/or hypertriglyceridemia. Design, Setting, and Participants Data on LDL-C levels and other lipid measures from 8656 patients seen at the National Institutes of Health Clinical Center between January 1, 1976, and June 2, 1999, were analyzed by the β-quantification reference method (18 715 LDL-C test results) and were randomly divided into equally sized training and validation data sets. Using TG and non–high-density lipoprotein cholesterol as independent variables, multiple least squares regression was used to develop an equation for very low-density lipoprotein cholesterol, which was then used in a second equation for LDL-C. Equations were tested against the internal validation data set and multiple external data sets of either β-quantification LDL-C results (n = 28 891) or direct LDL-C test results (n = 252 888). Statistical analysis was performed from August 7, 2018, to July 18, 2019. Main Outcomes and Measures Concordance between calculated and measured LDL-C levels by β-quantification, as assessed by various measures of test accuracy (correlation coefficient [R2], root mean square error [RMSE], mean absolute difference [MAD]), and percentage of patients misclassified at LDL-C treatment thresholds of 70, 100, and 190 mg/dL. Results Compared with β-quantification, the new equation was more accurate than other LDL-C equations (slope, 0.964; RMSE = 15.2 mg/dL;R2 = 0.9648; vs Friedewald equation: slope, 1.056; RMSE = 32 mg/dL;R2 = 0.8808; vs Martin equation: slope, 0.945; RMSE = 25.7 mg/dL;R2 = 0.9022), particularly for patients with hypertriglyceridemia (MAD = 24.9 mg/dL; vs Friedewald equation: MAD = 56.4 mg/dL; vs Martin equation: MAD = 44.8 mg/dL). The new equation calculates the LDL-C level in patients with TG levels up to 800 mg/dL as accurately as the Friedewald equation does for TG levels less than 400 mg/dL and was associated with 35% fewer misclassifications when patients with hypertriglyceridemia (TG levels, 400-800 mg/dL) were categorized into different LDL-C treatment groups. Conclusions and Relevance The new equation can be readily implemented by clinical laboratories with no additional costs compared with the standard lipid panel. It will allow for more accurate calculation of LDL-C level in patients with low LDL-C levels and/or hypertriglyceridemia (TG levels, ≤800 mg/dL) and thus should improve the use of LDL-C level in cardiovascular disease risk management.

Sex Differences in Blood Pressure Trajectories Over the Life Course.

Abstract: Importance If we assume that women and men exhibit variations of the same fundamental vascular physiology, then conventional analyses of subclinical measures would suggest that women catch up to men by midlife in the extent of potentially important vascular disease. Alternatively, under the assumption that vascular physiology may fundamentally differ between women and men, a sex-specific analysis of existing data could offer new insights and augment our understanding of sex differences in cardiovascular diseases. Objective To evaluate whether longitudinal patterns of blood pressure (BP) elevation differ between women and men during the life course when considering baseline BP levels as the reference. Design, Setting, and Participants We conducted sex-specific analyses of longitudinal BP measures (144 599 observations) collected for a period of 43 years (1971 to 2014) in 4 community-based US cohort studies. The combined total included 32 833 participants (54% female) spanning ages 5 to 98 years. Data were analyzed between May 4, 2019, and August 5, 2019. Exposures Age and serially assessed longitudinal BP measures: systolic BP, diastolic BP, mean arterial pressure (MAP), and pulse pressure (PP). Main Outcomes and Measures Sex-specific change in each primary BP measure compared with baseline BP levels, derived from multilevel longitudinal models fitted over the age span, and new-onset cardiovascular disease events. Results Of the 32 833 participants, 17 733 were women (54%). Women compared with men exhibited a steeper increase in BP that began as early as in the third decade and continued through the life course (likelihood ratio test χ2 = 531 for systolic BP; χ2 = 123 for diastolic BP; χ2 = 325 for MAP; and χ2 = 572 for PP;Pfor all Conclusions and Relevance In contrast with the notion that important vascular disease processes in women lag behind men by 10 to 20 years, sex-specific analyses indicate that BP measures actually progress more rapidly in women than in men, beginning early in life. This early-onset sexual dimorphism may set the stage for later-life cardiovascular diseases that tend to present differently, not simply later, in women compared with men.

Characteristics and Outcomes of Recipients of Heart Transplant With Coronavirus Disease 2019.

Abstract: Importance Recipients of heart transplant (HT) may be at increased risk of adverse outcomes attributable to infection with coronavirus disease 2019 (COVID-19) because of multiple comorbidities and clinically significant immunosuppression. Objective To describe the characteristics, treatment, and outcomes of recipients of HT with COVID-19. Design, Setting, and Participants This case series from a single large academic heart transplant program in New York, New York, incorporates data from between March 1, 2020, and April 24, 2020. All recipients of HT followed up by this center who were infected with COVID-19 were included. Interventions Heart transplant and a confirmed diagnosis of COVID-19. Main Outcomes and Measures The primary measure was vital status at end of study follow-up. Secondary measures included patient characteristics, laboratory analyses, changes to immunosuppression, and treatment administered for COVID-19. Results Twenty-eight patients with HT received a confirmed diagnosis of COVID-19. The median age was 64.0 (interquartile range [IQR], 53.5-70.5) years, 22 (79%) were men, and the median time from HT was 8.6 (IQR, 4.2-14.5) years. Comorbid conditions included hypertension in 20 patients (71%), diabetes in 17 patients (61%), and cardiac allograft vasculopathy in 16 patients (57%). Twenty-two participants (79%) were admitted for treatment, and 7 (25%) required mechanical ventilation. Most (13 of 17 [76%]) had evidence of myocardial injury (median high-sensitivity troponin T, 0.055 [IQR, 0.0205-0.1345] ng/mL) and elevated inflammatory biomarkers (median peak high-sensitivity C-reactive protein, 11.83 [IQR, 7.44-19.26] mg/dL; median peak interleukin 6, 105 [IQR, 38-296] pg/mL). Among patients managed at the study institution, mycophenolate mofetil was discontinued in 16 patients (70%), and 6 (26%) had a reduction in the dose of their calcineurin inhibitor. Treatment of COVID-19 included hydroxychloroquine (18 patients [78%]), high-dose corticosteroids (8 patients [47%]), and interleukin 6 receptor antagonists (6 patients [26%]). Overall, 7 patients (25%) died. Among 22 patients (79%) who were admitted, 11 (50%) were discharged home, 4 (18%) remain hospitalized at the end of the study, and 7 (32%) died during hospitalization. Conclusions and Relevance In this single-center case series, COVID-19 infection was associated with a case fatality rate of 25% in recipients of HT. Immunosuppression was reduced in most of this group of patients. Further study is required to evaluate the optimal approach to management of COVID-19 infection in the HT population.

Off-label Use of Direct Oral Anticoagulants Compared With Warfarin for Left Ventricular Thrombi.

Abstract: Importance Left ventricular (LV) thrombi can arise in patients with ischemic and nonischemic cardiomyopathies. Anticoagulation is thought to reduce the risk of stroke or systemic embolism (SSE), but there are no high-quality data on the effectiveness of direct oral anticoagulants (DOACs) for this indication. Objective To compare the outcomes associated with DOAC use and warfarin use for the treatment of LV thrombi. Design, Setting, and Participants A cohort study was performed at 3 tertiary care academic medical centers among 514 eligible patients with echocardiographically diagnosed LV thrombi between October 1, 2013, and March 31, 2019. Follow-up was performed through the end of the study period. Exposures Type and duration of anticoagulant use. Main Outcomes and Measures Clinically apparent SSE. Results A total of 514 patients (379 men; mean [SD] age, 58.4 [14.8] years) with LV thrombi were identified, including 300 who received warfarin and 185 who received a DOAC (64 patients switched treatment between these groups). The median follow-up across the patient cohort was 351 days (interquartile range, 51-866 days). On unadjusted analysis, DOAC treatment vs warfarin use (hazard ratio [HR], 2.71; 95% CI, 1.31-5.57;P = .01) and prior SSE (HR, 2.13; 95% CI, 1.22-3.72;P = .01) were associated with SSE. On multivariable analysis, anticoagulation with DOAC vs warfarin (HR, 2.64; 95% CI, 1.28-5.43;P = .01) and prior SSE (HR, 2.07; 95% CI, 1.17-3.66;P = .01) remained significantly associated with SSE. Conclusions and Relevance In this multicenter cohort study of anticoagulation strategies for LV thrombi, DOAC treatment was associated with a higher risk of SSE compared with warfarin use, even after adjustment for other factors. These results challenge the assumption of DOAC equivalence with warfarin for LV thrombi and highlight the need for prospective randomized clinical trials to determine the most effective treatment strategies for LV thrombi.

Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action

Abstract: Importance: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. The lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. The World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. The World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH. Observations: In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. The Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created. Conclusions and Relevance: By adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well.

Association of Monogenic vs Polygenic Hypercholesterolemia With Risk of Atherosclerotic Cardiovascular Disease.

Abstract: Importance Monogenic familial hypercholesterolemia (FH) is associated with lifelong elevations in low-density lipoprotein cholesterol (LDL-C) levels and increased risk of atherosclerotic cardiovascular disease (CVD). However, many individuals with hypercholesterolemia have a polygenic rather than a monogenic cause for their condition. It is unclear if a genetic variant for hypercholesterolemia alters the risk of CVD. Objectives To assess whether a genetic variant for hypercholesterolemia alters the risk of atherosclerotic CVD and to evaluate how this risk compares with that of nongenetic hypercholesterolemia. Design, Setting, and Participants In this genetic-association, case-control, cohort study, individuals aged 40 to 69 years were recruited by the UK Biobank from across the United Kingdom between March 13, 2006, and October 1, 2010, and followed up until March 31, 2017. Genotyping array and exome sequencing data from the UK Biobank cohort were used to identify individuals with monogenic (LDLR,APOB, andPCSK9) or polygenic hypercholesterolemia (LDL-C polygenic score >95th percentile based on 223 single-nucleotide variants in the entire cohort). The data were analyzed from July 1, 2019, to December 30, 2019. Main Outcomes and Measures The study investigated the association of genotype with the risk of coronary and carotid revascularization, myocardial infarction, ischemic stroke, and all-cause mortality among the overall study population and among participants with monogenic FH (n = 277), polygenic hypercholesterolemia (n = 2379), or hypercholesterolemia with undetermined cause (n = 2232) at comparable levels of LDL-C measured at study enrollment. Results For the 48 741 individuals with genotyping array and exome sequencing data, the mean (SD) age was 56.6 (8.0) years, and 54.5% were female (n = 26 541 of 48 741). A monogenic FH variant for hypercholesterolemia was found in 277 individuals (0.57%, 1 in 176 individuals). Participants with monogenic FH were significantly more likely than those without monogenic FH to experience an atherosclerotic CVD event at 55 years or younger (17 of 277 [6.1%] vs 988 of 48 464 [2.0%];P Conclusions and Relevance The findings of this study suggest that among individuals with hypercholesterolemia, genetic determinants of LDL-C levels may impose additional risk of CVD. Thus, understanding the possible genetic cause of hypercholesterolemia may provide important prognostic information to treat patients.

Association of Troponin Levels With Mortality in Italian Patients Hospitalized With Coronavirus Disease 2019: Results of a Multicenter Study.

Abstract: Importance Myocardial injury, detected by elevated plasma troponin levels, has been associated with mortality in patients hospitalized with coronavirus disease 2019 (COVID-19). However, the initial data were reported from single-center or 2-center studies in Chinese populations. Compared with these patients, European and US patients are older, with more comorbidities and higher mortality rates. Objective To evaluate the prevalence and prognostic value of myocardial injury, detected by elevated plasma troponin levels, in a large population of White Italian patients with COVID-19. Design, Setting, and Participants This is a multicenter, cross-sectional study enrolling consecutive patients with laboratory-confirmed COVID-19 who were hospitalized in 13 Italian cardiology units from March 1 to April 9, 2020. Patients admitted for acute coronary syndrome were excluded. Elevated troponin levels were defined as values greater than the 99th percentile of normal values. Main Outcomes and Measures Clinical characteristics and outcomes stratified as elevated or normal cardiac troponin levels at admission, defined as troponin T or troponin I at a level greater than the 99th percentile of normal values. Results A total of 614 patients with COVID-19 were included in this study (mean age [SD], 67 [13] years; 70.8% male), of whom 148 patients (24.1%) died during the hospitalization. Elevated troponin levels were found in 278 patients (45.3%). These patients were older (mean [SD] age, 64.0 [13.6] years vs 71.3 [12.0] years;P Conclusions and Relevance In this multicenter, cross-sectional study of Italian patients with COVID-19, elevated troponin was an independent variable associated with in-hospital mortality and a greater risk of cardiovascular and noncardiovascular complications during a hospitalization for COVID-19.

Case Rates, Treatment Approaches, and Outcomes in Acute Myocardial Infarction During the Coronavirus Disease 2019 Pandemic.

Abstract: Importance The coronavirus disease 2019 (COVID-19) pandemic has changed health care delivery worldwide. Although decreases in hospitalization for acute myocardial infarction (AMI) have been reported during the pandemic, the implication for in-hospital outcomes is not well understood. Objective To define changes in AMI case rates, patient demographics, cardiovascular comorbidities, treatment approaches, and in-hospital outcomes during the pandemic. Design, Setting, and Participants This cross-sectional study retrospectively analyzed AMI hospitalizations that occurred between December 30, 2018, and May 16, 2020, in 1 of the 49 hospitals in the Providence St Joseph Health system located in 6 states (Alaska, Washington, Montana, Oregon, California, and Texas). The cohort included patients aged 18 years or older who had a principal discharge diagnosis of AMI (ST-segment elevation myocardial infarction [STEMI] or non–ST-segment elevation myocardial infarction [NSTEMI]). Segmented regression analysis was performed to assess changes in weekly case volumes. Cases were grouped into 1 of 3 periods: before COVID-19 (December 30, 2018, to February 22, 2020), early COVID-19 (February 23, 2020, to March 28, 2020), and later COVID-19 (March 29, 2020, to May 16, 2020). In-hospital mortality was risk-adjusted using an observed to expected (O/E) ratio and covariate-adjusted multivariable model. Exposure Date of hospitalization. Main Outcomes and Measures The primary outcome was the weekly rate of AMI (STEMI or NSTEMI) hospitalizations. The secondary outcomes were patient characteristics, treatment approaches, and in-hospital outcomes of this patient population. Results The cohort included 15 244 AMI hospitalizations (of which 4955 were for STEMI [33%] and 10 289 for NSTEMI [67%]) involving 14 724 patients (mean [SD] age of 68 [13] years and 10 019 men [66%]). Beginning February 23, 2020, AMI-associated hospitalizations decreased at a rate of –19.0 (95% CI, –29.0 to –9.0) cases per week for 5 weeks (early COVID-19 period). Thereafter, AMI-associated hospitalizations increased at a rate of +10.5 (95% CI, +4.6 to +16.5) cases per week (later COVID-19 period). No appreciable differences in patient demographics, cardiovascular comorbidities, and treatment approaches were observed across periods. The O/E mortality ratio for AMI increased during the early period (1.27; 95% CI, 1.07-1.48), which was disproportionately associated with patients with STEMI (1.96; 95% CI, 1.22-2.70). Although the O/E mortality ratio for AMI was not statistically different during the later period (1.23; 95% CI, 0.98-1.47), increases in the O/E mortality ratio were noted for patients with STEMI (2.40; 95% CI, 1.65-3.16) and after risk adjustment (odds ratio, 1.52; 95% CI, 1.02-2.26). Conclusions and Relevance This cross-sectional study found important changes in AMI hospitalization rates and worse outcomes during the early and later COVID-19 periods. Future studies are needed to identify contributors to the increased mortality rate among patients with STEMI.

Association of Bempedoic Acid Administration With Atherogenic Lipid Levels in Phase 3 Randomized Clinical Trials of Patients With Hypercholesterolemia.

Abstract: Importance Additional lipid-lowering therapy options are needed for patients who cannot achieve sufficient decreases in low-density lipoprotein cholesterol (LDL-C) levels using statins alone or for those who are statin intolerant. Objective To conduct a pooled analysis of phase 3 randomized clinical trials of bempedoic acid vs placebo. Design, Setting, and Participants This analysis pooled data from 4 double-blind, placebo-controlled randomized clinical trials conducted from 2016 to 2018. Patients were enrolled in North America and Europe. Eligibility criteria included hypercholesterolemia while receiving stable lipid-lowering therapy and high cardiovascular risk or hypercholesterolemia and statin intolerance. Interventions Patients were randomized 2:1 to bempedoic acid, 180 mg (n = 2425), or placebo (n = 1198) once daily for 12 to 52 weeks. Main Outcomes and Measures Primary efficacy end point was percentage change from baseline in LDL-C level at week 12 in the intention-to-treat population. Patients were parsed into 2 groups according to enrollment criteria: (1) patients with hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) or with heterozygous familial hypercholesterolemia (HeFH) or with both and receiving statins and (2) patients with hypercholesterolemia who were statin intolerant receiving maximally tolerated statins. Results In this analysis of 3623 patients, the overall mean (SD) patient age was 65.5 (9.2) years (similar in both pools). Among patients with ASCVD or HeFH or both, the mean (SD) baseline LDL-C level was 107.6 (32.7) mg/dL. At week 12, the LDL-C level percentage change from baseline was −16.0% with bempedoic acid vs 1.8% with placebo (difference, −17.8%; 95% CI, −19.5% to −16.0%;P Conclusions and Relevance Bempedoic acid added to maximally tolerated statins, including moderate- or high-intensity statins or no background statin, was associated with decreased LDL-C levels vs placebo in patients with hypercholesterolemia with an acceptable safety profile. As a nonstatin adjunct or statin alternative, bempedoic acid has potential for use in a broad spectrum of patients. Trial Registration ClinicalTrials.gov Identifiers:NCT02666664,NCT02991118,NCT03001076, andNCT02988115

One-Year Outcomes of Mitral Valve-in-Valve Using the SAPIEN 3 Transcatheter Heart Valve

Abstract: Importance Bioprosthetic mitral valves are implanted with increasing frequency but inevitably degenerate, leading to heart failure. Reoperation is associated with high morbidity and mortality. Transcatheter mitral valve-in-valve (MViV) using balloon-expandable transcatheter valves has emerged as an alternative for high-surgical risk patients. Objective To assess contemporary outcomes of SAPIEN 3 (Edwards Lifesciences) MViV replacement. Design, setting, and participants In this registry-based prospective cohort study of SAPIEN 3 MViV, patients entered in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry from June 2015 to July 2019 were analyzed. US Centers for Medicare and Medicaid linkage ensured comprehensive collection of death and stroke data. Exposures Mitral valve-in-valve for degenerated bioprosthetic mitral valves. Main outcomes and measures The primary efficacy end point was 1-year mortality. The primary safety end point was procedural technical success as defined by the Mitral Valve Academic Research Consortium criteria. Secondary end points included 30-day mortality, New York Heart Association-defined heart failure, and mitral valve performance. Results A total of 1529 patients (mean [SD] age, 73.3 [11.84] years; 904 women [59.1%]) underwent transseptal or transapical MViV implant at 295 hospitals between June 2015 and July 2019. The mean (SD) Society of Thoracic Surgeons predicted risk of mortality was 11.1% (8.7%). Procedural technical success was achieved for 1480 of 1529 patients (96.8%). All-cause mortality was 5.4% at 30 days and 16.7% at 1 year. Transseptal access was associated with lower 1-year all-cause mortality than transapical access (15.8% vs 21.7%; P = .03). Transcatheter MViV led to early, sustained, and clinically meaningful improvements in heart failure (class III/IV New York Heart Association heart failure of 87.1% at baseline vs 9.7% at 1 year). The mean (SD) mitral valve gradient at 1 year was 7 (2.89) mm Hg. Conclusions and relevance Transcatheter MViV using the SAPIEN 3 transcatheter heart valve is associated with high technical success, low 30-day and 1-year mortality, significant improvement of heart failure symptoms, and sustained valve performance. Transseptal MViV should be considered an option for most patients with failed surgical bioprosthetic valves and favorable anatomy.

Association of Normal Systolic Blood Pressure Level with Cardiovascular Disease in the Absence of Risk Factors

Abstract: Importance The risk of atherosclerotic cardiovascular disease (ASCVD) at currently defined normal systolic blood pressure (SBP) levels in persons without ASCVD risk factors based on current definitions is not well defined. Objective To examine the association of SBP levels with coronary artery calcium and ASCVD in persons without hypertension or other traditional ASCVD risk factors based on current definitions. Design, Setting, and Participants A cohort of 1457 participants free of ASCVD from the Multi-Ethnic Study of Atherosclerosis who were without dyslipidemia (low-density lipoprotein cholesterol level ≥160 mg/dL or high-density lipoprotein cholesterol level Exposures Systolic blood pressure. Main Outcomes and Measures Presence or absence of coronary artery calcium and incident ASCVD events. Results Of the 1457 participants, 894 were women (61.4%); mean (SD) age was 58.1 (9.8) years and mean (SD) follow-up was 14.5 (3.9) years. There was an increase in traditional ASCVD risk factors, coronary artery calcium, and incident ASCVD events with increasing SBP levels. The aHR for ASCVD was 1.53 (95% CI, 1.17-1.99) for every 10-mm Hg increase in SBP levels. Compared with persons with SBP levels 90 to 99 mm Hg, the aHR for ASCVD risk was 3.00 (95% CI, 1.01-8.88) for SBP levels 100 to 109 mm Hg, 3.10 (95% CI, 1.03-9.28) for SBP levels 110 to 119 mm Hg, and 4.58 (95% CI, 1.47-14.27) for SBP levels 120 to 129 mm Hg. Conclusions and Relevance Beginning at an SBP level as low as 90 mm Hg, there appears to be a stepwise increase in the presence of coronary artery calcium and the risk of incident ASCVD with increasing SBP levels. These results highlight the importance of primordial prevention for SBP level increase and other traditional ASCVD risk factors, which generally seem to have similar trajectories of graded increase in risk within values traditionally considered to be normal.

Effects of a 9-Week Hybrid Comprehensive Telerehabilitation Program on Long-term Outcomes in Patients With Heart Failure: The Telerehabilitation in Heart Failure Patients (TELEREH-HF) Randomized Clinical Trial.

Abstract: Importance Guidelines recommend exercise training as a component of heart failure management. There are large disparities in access to rehabilitation, and introducing hybrid comprehensive telerehabilitation (HCTR) consisting of remote monitoring of training at patients’ homes might be an appealing alternative. Objective To assess whether potential improvements in quality-of-life outcomes after a 9-week HCTR intervention in patients with heart failure translate into improvement in clinical outcomes during extended 12 to 24 months of follow-up, compared with usual care. Design, Setting, and Participants The Telerehabilitation in Heart Failure Patients (TELEREH-HF) trial is a multicenter, prospective, open-label, parallel-group randomized clinical trial that enrolled 850 patients with heart failure up to 6 months after a cardiovascular hospitalization with New York Heart Association levels I, II, or III and left ventricular ejection fraction of 40% or less. Patients from 5 centers in Poland were randomized 1:1 to HCTR plus usual care or usual care only and followed up for 14 to 26 months after randomization. Interventions During the first 9 weeks, patients underwent either an HCTR program (1 week in hospital and 8 weeks at home) or usual care with observation. The HCTR intervention encompassed telecare, telerehabilitation, and remote monitoring of implantable devices. No intervention occurred in the remaining study period. Main Outcomes and Measures The percentage of days alive and out of the hospital from randomization through the end of follow-up at 14 to 26 months. Results A total of 850 patients were enrolled, with 425 randomized to the HCTR group (377 male patients [88.7%]; mean [SD] age, 62.6 [10.8] years) and 425 randomized to usual care (376 male patients [88.5%]; mean [SD] age, 62.2 [10.2] years). The HCTR intervention did not extend the percentage of days alive and out of the hospital. The mean (SD) days were 91.9 (19.3) days in the HCTR group vs 92.8 (18.3) days in the usual-care group, with the probability that HCTR extends days alive and out of the hospital equal to 0.49 (95% CI, 0.46-0.53;P = .74) vs usual care. During follow-up, 54 patients died in the HCTR arm and 52 in the usual-care arm, with mortality rates at 26 months of 12.5% vs 12.4%, respectively (hazard ratio, 1.03 [95% CI, 0.70-1.51]). There were also no differences in hospitalization rates (hazard ratio, 0.94 [95% CI, 0.79-1.13]). The HCTR intervention was effective at 9 weeks, significantly improving peak oxygen consumption (0.95 [95% CI, 0.65-1.26] mL/kg/min vs 0.00 [95% CI, −0.31 to 0.30] mL/kg/min;P Conclusions and Relevance In this trial, the positive effects of a 9-week program of HCTR in patients with heart failure did not lead to the increase in percentage of days alive and out of the hospital and did not reduce mortality and hospitalization over a follow-up period of 14 to 26 months. Trial Registration ClinicalTrials.gov identifier:NCT02523560

Association of Clinical Outcomes With Left Ventricular Assist Device Use by Bridge to Transplant or Destination Therapy Intent: The Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) Randomized Clinical Trial.

Abstract: Importance Left ventricular assist devices (LVADs) are well established in the treatment of advanced heart failure, but it is unclear whether outcomes are different based on the intended goal of therapy in patients who are eligible vs ineligible for heart transplant. Objective To determine whether clinical outcomes in the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 (MOMENTUM 3) trial differed by preoperative categories of bridge to transplant (BTT) or bridge to transplant candidacy (BTC) vs destination therapy (DT). Design, Setting, and Participants This study was a prespecified secondary analysis of the MOMENTUM 3 trial, a multicenter randomized clinical trial comparing the magnetically levitated centrifugal-flow HeartMate 3 (HM3) LVAD to the axial-flow HeartMate II (HMII) pump. It was conducted in 69 centers with expertise in managing patients with advanced heart failure in the United States. Patients with advanced heart failure were randomized to an LVAD, irrespective of the intended goal of therapy (BTT/BTC or DT). Main Outcomes and Measures The primary end point was survival free of disabling stroke or reoperation to remove or replace a malfunctioning device at 2 years. Secondary end points included adverse events, functional status, and quality of life. Results Of the 1020 patients with implants (515 with HM3 devices [50.5%] and 505 with HMII devices [49.5%]), 396 (38.8%) were in the BTT/BTC group (mean [SD] age, 55 [12] years; 310 men [78.3%]) and 624 (61.2%) in the DT group (mean [SD] age, 63 [12] years; 513 men [82.2%]). Of the patients initially deemed as transplant ineligible, 84 of 624 patients (13.5%) underwent heart transplant within 2 years of LVAD implant. In the primary end point analysis, HM3 use was superior to HMII use in patients in the BTT/BTC group (76.8% vs 67.3% for survival free of disabling stroke and reoperation; hazard ratio, 0.62 [95% CI, 0.40-0.94]; log-rankP = .02) and patients in the DT group (73.2% vs 58.7%; hazard ratio, 0.61 [95% CI, 0.46-0.81]; log-rankP Conclusions and Relevance In this trial, the superior treatment effect of HM3 over HMII was similar for patients in the BTT/BTC or DT groups. It is possible that use of arbitrary categorizations based on current or future transplant eligibility should be clinically abandoned in favor of a single preimplant strategy: to extend the survival and improve the quality of life of patients with medically refractory heart failure. Trial Registration ClinicalTrials.gov identifier:NCT02224755

Development of Persistent Opioid Use After Cardiac Surgery

Abstract: Importance The overuse of opioids for acute pain management has led to an epidemic of persistent opioid use Objective To determine the proportion of opioid-naive patients who develop persistent opioid use after cardiac surgery and investigate the association between the initial amount of opioids prescribed at discharge and the likelihood of developing new persistent opioid use Design, Setting, and Participants This retrospective cohort study used data from a national administrative claims database from January 1, 2004, to December 31, 2016 and included 35 817 patients who underwent coronary artery bypass grafting (CABG) (25 673 [717%]) and heart valve (10 144 [283%]) procedures All patients were opioid-naive within 180 days before the index procedure and filled an opioid prescription within 14 days after surgery Exposures Opioid medications after cardiac surgery Main Outcomes and Measures The proportion of opioid-naive patients who developed new persistent opioid use within 90 to 180 days after surgery was determined Oral morphine equivalents (OMEs) were calculated for the first opioid prescription filled after discharge A multivariable logistic regression with cubic splines was used to analyze the association among the OMEs at discharge and likelihood of developing persistent opioid use Results Of the 25 673 patients who underwent CABG, the mean (SD) age for those without (n = 23 064) vs with (n = 2609) persistent opioid use was 629 (98) years vs 616 (97) years, respectively, and the number who were men were 18 758 (813%) vs 1998 (766%) Of the 10 144 patients who underwent heart valve surgery, the mean (SD) age for those without (n = 9343) vs with (n = 821) persistent opioid use was 632 (124) years vs 612 (125) years, respectively, and the number who were men were 6378 (683%) vs 511 (622%) Persistent opioid use is a substantial concern after cardiac surgery and occurred in 2609 patients undergoing CABG (102%) and 821 valve surgery patients (81%;P = 001) The likelihood for developing persistent opioid use was decreased among heart valve surgery recipients (odds ratio [OR], 078;P Conclusions and Relevance Opioids are used extensively after cardiothoracic surgery and nearly 1 of 10 patients will continue to use opioids over 90 days after surgery Furthermore, higher OMEs prescribed at discharge were significantly associated with developing persistent use Centers must adopt protocols to increase patient education and limit opioid prescriptions after discharge