BACKGROUND There is no known effective therapy for patients with coronavirus disease 2019 . Initial reports suggesting the potential benefit of hydroxychloroquine/azithromycin (HY/ AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns about the potential risk of QT interval prolongation and induction of torsade de pointes (TdP).OBJECTIVE The purpose of this study was to assess the change in corrected QT (QTc) interval and arrhythmic events in patients with COVID-19 treated with HY/AZ.METHODS This is a retrospective study of 251 patients from 2 centers who were diagnosed with COVID-19 and treated with HY/AZ. We reviewed electrocardiographic tracings from baseline and until 3 days after the completion of therapy to determine the progression of QTc interval and the incidence of arrhythmia and mortality. RESULTSThe QTc interval prolonged in parallel with increasing drug exposure and incompletely shortened after its completion.Extreme new QTc interval prolongation to .500 ms, a known marker of high risk of TdP, had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc interval of patients exhibiting extreme QTc interval prolongation was normal.CONCLUSION The combination of HY/AZ significantly prolongs the QTc interval in patients with COVID-19. This prolongation may be responsible for life-threatening arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in light of its unproven efficacy. Strict QTc interval monitoring should be performed if the regimen is given.
Background-The prevalence and clinical significance of isolated office (or white coat) hypertension is controversial, and population data are limited. We studied the prevalence of this condition and its association with echocardiographic left ventricular mass in the general population of the PAMELA (Pressione Arteriose Monitorate E Loro Associazioni) Study. Methods and Results-The study involved a large, randomized sample (nϭ3200) representative of the Monza (Milan) population, 25 to 74 years of age. Participants in the study (64% of the sample) underwent measurements of office, home, 24-hour ambulatory blood pressure, and echocardiography. Isolated office hypertension was defined as systolic or diastolic values Ն140 mm Hg or Ն90 mm Hg, respectively. Home and ambulatory normotension were defined according to criteria previously established from the PAMELA Study, for example, Ͻ132/83 mm Hg (systolic/diastolic) for home and 125/79 mm Hg for 24-hour average blood pressure. Treated hypertensive subjects were excluded from analysis that was made on a total of 1637 subjects. Depending on normotension being established on systolic or diastolic blood pressure measured at home or over 24 hours, the prevalence of isolated office hypertension ranged from 9% to 12%. In these subjects, left ventricular mass index was greater (PϽ0.01) than in subjects with normotension both in and outside the office. This was the case also for prevalence of left ventricular hypertrophy. Left ventricular mass index and hypertrophy were similarly greater in subjects found to have normal office but elevated home or ambulatory blood pressure (Ϸ10% of the population). Conclusions-Isolated office hypertension has a noticeable prevalence in the population and is accompanied by structural cardiac alterations, suggesting that it is not an entirely harmless phenomenon. This is the case also for the opposite condition, that is, normal office but elevated home or ambulatory blood pressure, which implies that limiting blood pressure measurements to office values may not suffice in identification of subjects at risk.
IMPORTANCE Myocardial injury, detected by elevated plasma troponin levels, has been associated with mortality in patients hospitalized with coronavirus disease 2019 . 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 MEASURESClinical 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 < .001) and had higher prevalence of hypertension (168 patients [50.5%] vs 182 patients [65.9%]; P < .001), heart failure (24 [7.2%]; 63 [22.8%]; P < .001), coronary artery disease (50 [15.0%] vs 87 [31.5%]; P < .001), and atrial fibrillation (33 [9.9%] vs 67 [24.3%]; P < .001). Elevated troponin levels were associated with an increased in-hospital mortality (37% vs 13%; HR, 1.71 [95% CI, 1.13-2.59]; P = .01 via multivariable Cox regression analysis), and this was independent from concomitant cardiac disease. Elevated troponin levels were also associated with a higher risk of in-hospital complications: heart failure (44 patients [19.2%] vs 7 patients [2.9%]; P < .001), sepsis (31 [11.7%] vs 21 [6.4%]; P = .03), acute kidney failure (41 [20.8%] vs 13 [6.2%]; P < .001), multiorgan failure (21 [10.9%] vs 6 [2.9%]; P = .003), pulmonary embolism (27 [9.9%] vs 17 [5.2%]; P = .04), delirium (13 [6.8%] vs 3 [1.5%]; P = .02), and major bleeding (16 [7.0%] vs 4 [1.6%]; P = .008). CONCLUSIONS AND RELEVANCEIn 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.
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