Background Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis. However, the mechanisms of myocardial injury remain unclear and prior studies have not reported cardiovascular imaging data. Objectives This study sought to characterize the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19. Methods We conducted an international, multicenter cohort study including 7 hospitals in New York City and Milan of hospitalized patients with laboratory-confirmed COVID-19 who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization. Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization. Results A total of 305 patients were included. Mean age was 63 years and 205 patients (67.2%) were male. Overall, myocardial injury was observed in 190 patients (62.3%). Compared with patients without myocardial injury, those with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities that included left ventricular wall motion abnormalities, global left ventricular dysfunction, left ventricular diastolic dysfunction grade II or III, right ventricular dysfunction and pericardial effusions. Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities. Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death but not myocardial injury without TTE abnormalities. Conclusions Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury. Myocardial injury was associated with increased in-hospital mortality particularly if echocardiographic abnormalities were present.

Coronavirus disease 2019 (COVID-19) is a pandemic that has affected more than 1.8 million people worldwide, overwhelmed health care systems owing to the high proportion of critical presentations, and resulted in more than 100,000 deaths. Since the first data analyses in China, elevated cardiac troponin has been noted in a substantial proportion of patients, implicating myocardial injury as a possible pathogenic mechanism contributing to severe illness and mortality. Accordingly, high troponin levels are associated with increased mortality in patients with COVID-19. This brief review explores the available evidence regarding the association between COVID-19 and myocardial injury.

Background-In heart failure (HF), a defective nitric oxide signaling is involved in left ventricular (LV) diastolic abnormalities and remodeling. PDE5 inhibition, by blocking degradation of nitric oxide second-messenger cyclic guanosine monophosphate, might be beneficial. In a cohort of systolic HF patients, we tested the effects of PDE5 inhibition (sildenafil) on LV ejection fraction, diastolic function, cardiac geometry, and clinical status. Methods and Results-Forty-five HF patients (New York Heart Association class II-III) were randomly assigned to placebo or sildenafil (50 mg three times per day) for 1 year, with assessment (6 months and 1 year) of LV ejection fraction, diastolic function, geometry, cardiopulmonary exercise performance, and quality of life. In the sildenafil group only, at 6 months and 1 year, LV ejection fraction, early diastolic tissue Doppler velocities (EЈ) at the mitral lateral (from 4.62 to 5.20 and 5.19 m/s) and septal (from 4.71 to 5.23 and 5.24 m/s) annuli significantly increased, whereas the ratio of early transmitral (E) to EЈ lateral decreased (from 13.1 to 9.8 to 9.4) (PϽ0.01). Changes were accompanied by a reverse remodeling of left atrial volume index (from 32.0 to 29.0 and 29.1 mL/m

In CHF, improvement in exercise ventilation and aerobic efficiency with sildenafil is sustained and is significantly related with an endothelium-mediated attenuation of exercising muscle oversignaling. Chronic sildenafil seems to be a remedy based on CHF pathophysiology and devoid of remarkable adverse effects.

Background-The prevalence of heart failure with preserved ejection fraction is increasing. The prognosis worsens with pulmonary hypertension and right ventricular (RV) failure development. We targeted pulmonary hypertension and RV burden with the phosphodiesterase-5 inhibitor sildenafil. Methods and Results-Forty-four patients with heart failure with preserved ejection fraction (heart failure signs and symptoms, diastolic dysfunction, ejection fraction Ն50%, and pulmonary artery systolic pressure Ͼ40 mm Hg) were randomly assigned to placebo or sildenafil (50 mg thrice per day). At 6 months, there was no improvement with placebo, but sildenafil mediated significant improvements in mean pulmonary artery pressure (Ϫ42.0Ϯ13.0%) and RV function, as suggested by leftward shift of the RV Frank-Starling relationship, increased tricuspid annular systolic excursion (ϩ69.0Ϯ19.0%) and ejection rate (ϩ17.0Ϯ8.3%), and reduced right atrial pressure (Ϫ54.0Ϯ7.2%). These effects may have resulted from changes within the lung (reduced lung water content and improved alveolar-capillary gas conductance, ϩ15.8Ϯ4.5%), the pulmonary vasculature (arteriolar resistance, Ϫ71.0Ϯ8.2%), and left-sided cardiac function (wedge pulmonary pressure, Ϫ15.7Ϯ3.1%; cardiac index, ϩ6.0Ϯ0.9%; deceleration time, Ϫ13.0Ϯ1.9%; isovolumic relaxation time, Ϫ14.0Ϯ1.7%; septal mitral annulus velocity, Ϫ76.4Ϯ9.2%). Results were similar at 12 months. Conclusions-The multifaceted response to phosphodiesterase-5 inhibition in heart failure with preserved ejection fraction includes improvement in pulmonary pressure and vasomotility, RV function and dimension, left ventricular relaxation and distensibility (structural changes and/or ventricular interdependence), and lung interstitial water metabolism (wedge pulmonary pressure decrease improving hydrostatic balance and right atrial pressure reduction facilitating lung lymphatic drainage). These results enhance our understanding of heart failure with preserved ejection fraction and offer new directions for therapy. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01156636.

Background-The six-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) are the 2 testing modalities most broadly used for assessing functional limitation in patients with heart failure (HF). A comprehensive comparison on clinical and prognostic validity of the 2 techniques has not been performed and is the aim of the present investigation. Methods and Results-Two hundred fifty-three patients diagnosed with systolic (nϭ211) or diastolic (nϭ42) HF (age:61.9Ϯ10.1 years; New York Heart Association Class: 2.2Ϯ0.78) underwent a 6MWT and a symptom-limited CPET evaluation and were prospectively followed up. During the 4-year tracking period, there were 43 cardiac-related deaths with an annual cardiac mortality rate of 8.7%. The 6MWT distance correlated with CPET-derived variables (ie, peak VO 2 , VO 2 at anaerobic threshold, and VE/VCO 2 slope) and was significantly reduced in proportion with lower peak VO 2 and higher VE/VCO 2 slope classes and presence of an exercise oscillatory breathing (EOB) pattern (PϽ0.01). However, no significant differences were observed in distance covered between survivors and nonsurvivors (353.2Ϯ95.8 m versus 338.5Ϯ76.4 m; PϭNS). At univariate and multivariate Cox proportional analyses, the association of the 6MWT distance with survival was not significant either as a continuous or dicotomized variable (Յ300 m). Conversely, CPET-derived variables emerged as prognostic with the strongest association found for EOB (systolic HF) and VE/VCO 2 slope (entire population with HF and patients with a 6MWTՅ300 m). Conclusions-The 6MWT is confirmed to be a simple and reliable first-line test for quantification of exercise intolerance in patients with HF. However, there is no supportive evidence for its use as a prognostic marker in alternative to or in conjunction with CPET-derived variables. (Circ Heart Fail. 2009;2:549-555.)

AimsExercise oscillatory breathing (EOB) is a ventilatory abnormality that occurs in 20% of heart failure (HF) patients and carries a very unfavourable prognosis. Pulmonary vasoconstriction has been suggested to be involved in this disorder. We hypothesized that modulation of pulmonary vascular hypertone by oversignalling of the nitric oxide pathway with phosphodiesterase 5 (PDE5) inhibition might be beneficial. Accordingly, we performed a 1-year pilot trial with sildenafil in patients with HF and EOB. Methods and resultsAmong 122 HF cases, 32 presented with EOB during cardiopulmonary exercise testing (CPX) and were randomized to receive placebo (n ¼ 16) or sildenafil (n ¼ 16) at the dose of 50 mg three times a day, in addition to their current antifailure treatment. CPX-derived variables and pulmonary haemodynamics were assessed at 6 and 12 months. Sildenafil reversed EOB in 87% of patients at 6 months and 93% at 1 year, respectively (P , 0.01). This effect was accompanied by an improvement in functional performance (peak VO 2 ; from 9.6 to 12.4 and 13.2 mL/min/kg; P , 0.01) and exercise ventilation efficiency (ventilation to CO 2 production slope; from 41.1 to 32.7 and 31.5; P , 0.01). Chronic treatment with PDE5 inhibition significantly decreased pulmonary capillary wedge pressure (from 21 to 14 and 14 mmHg), mean pulmonary artery pressure (PAP; from 34.8 to 23 and 24 mmHg), and pulmonary vascular resistance (PVR; from 360 to 270 and 266 dyne/s/cm 5 ) compared with placebo (P , 0.01 for each comparison). On exploratory analysis, there was a correlation between PAP and PVR and the decrease in EOB in the treatment group. Placebo did not alter any of the aforementioned variables. ConclusionsPDE5 inhibition in HF patients with EOB offers the dual advantage of improving functional capacity and modulating the EOB pattern. PAP and PVR reduction seem to underlie the correction of the breathing disorder. Whether reversal of this unfavourable prognostic signal can affect survival remains unconfirmed at the moment.--

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