Thirty-year trends and outcome of isolated versus combined group 2 pulmonary hypertension after cardiac transplantation.

Aim: To investigate the effect of the new definition of pulmonary hypertension (PH) and new pulmonary vascular resistance (PVR) thresholds on the prevalence, clinical characteristics, and events following cardiac transplantation (CTx) over 30 years. Methods: Patients who underwent CTx between 1983 and 2014 for whom invasive hemodynamic data was available were analyzed (n = 342). Patients transplanted between 1983 and 1998 were classified as early era and those transplanted between 1999 and 2014 were classified as recent era. Group 2 PH was diagnosed in the presence of a mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary capillary wedge pressure (PCWP) > 15 mmHg. Isolated post capillary PH (Ipc-PH) was defined as PVR ≤ 2 wood units and combined pre and post capillary PH (Cpc-PH) was defined PVR > 2 wood units. Moderate to severe PH was defined as mPAP ≥ 35 mmHg. The primary outcome was 30-day mortality and long-term mortality according to type and severity of PH. Proportions were analyzed using the chi-square test, and survival analyses were performed using Kaplan-Meier curves and compared using the logrank test. Results: The prevalence of PH in patients transplanted in the early era was 89.1%, whilst 84.2% of patients transplanted in the recent era had PH (p = 0.3914). There was no difference in the prevalence of a pre-capillary component according to era (p = 0.4001), but severe PH was more common in the early era (51.1% [early] vs 38.0% [recent] p = 0.0151). Thirty-day and long-term  mortality  were  not  significantly  associated  with severity or type of PH. There was a trend toward increased 30-day mortality in mild PH (10.1%), compared to no PH (4.4%) and moderate to severe PH (6.6%; p = 0.0653). Long-term mortality did not differ according to the severity of PH (p = 0.1480). There were no significant differences in 30-day or long-term mortality in IpcPH compared to CpcPH (p = 0.3974 vs p = 0.5767, respectively). Conclusion: Over 30 years, PH has remained very prevalent before CTx. The presence, severity, and type (pre- vs post-capillary) of PH is not significantly associated with short- or long-term mortality.

Fourteen-Day Evolution of COVID-19 Symptoms during the Third Wave in Nonvaccinated Subjects and Effects of Hesperidin Therapy: A Randomized, Double-Blinded, Placebo-Controlled Study.

COVID-19 symptoms can cause substantial disability, yet no therapy can currently reduce their frequency or duration. We conducted a double-blind placebo-controlled trial of hesperidin 1000 mg once daily for 14 days in 216 symptomatic nonvaccinated COVID-19 subjects. Thirteen symptoms were recorded after 3, 7, 10, and 14 days. The primary endpoint was the proportion of subjects with any of four cardinal (group A) symptoms: fever, cough, shortness of breath, or anosmia. At the baseline, symptoms in decreasing frequency were as follows: cough (53.2%), weakness (44.9%), headache (42.6%), pain (35.2%), sore throat (28.7%), runny nose (26.9%), chills (22.7%), shortness of breath (22.2%), anosmia (18.5%), fever (16.2%), diarrhea (6.9%), nausea/vomiting (6.5%), and irritability/confusion (3.2%). Group A symptoms in the placebo vs. hesperidin group were 88.8% vs. 88.5% (day 1) and reduced to 58.5 vs. 49.4% at day 14 (OR 0.69, 95% CI 0.38-1.27, p = 0.23). At day 14, 15 subjects in the placebo group and 28 in the hesperidin group failed to report their symptoms. In an attrition bias analysis imputing "no symptoms" to missing values, the hesperidin group showed reduction of 14.5% of group A symptoms from 50.9% to 36.4% (OR: 0.55, 0.32-0.96, p = 0.03). Anosmia, the most frequent persisting symptom (29.3%), was lowered by 7.3% to 25.3% in the hesperidin group vs. 32.6% in the placebo group (p = 0.29). The mean number of symptoms in the placebo and hesperidin groups was 5.10 (SD 2.26) vs. 5.48 (SD 2.35) (day 1) and 1.40 (SD 1.65) vs. 1.38 (SD 1.76) (day 14) (p = 0.92). In conclusion, most nonvaccinated COVID-19 infected subjects remain symptomatic after 14 days with anosmia being the most frequently persisting symptom. Hesperidin 1 g daily may help reduce group A symptoms. Earlier treatment of longer duration and/or higher dosage should be tested.