Electrical storm treatment by percutaneous stellate ganglion block: the STAR study.

BACKGROUND AND AIMS: An electrical storm (ES) is a clinical emergency with a paucity of established treatment options. Despite initial encouraging reports about the safety and effectiveness of percutaneous stellate ganglion block (PSGB), many questions remained unsettled and evidence from a prospective multicentre study was still lacking. For these purposes, the STAR study was designed. METHODS: This is a multicentre observational study enrolling patients suffering from an ES refractory to standard treatment from 1 July 2017 to 30 June 2023. The primary outcome was the reduction of treated arrhythmic events by at least 50% comparing the 12 h following PSGB with the 12 h before the procedure. STAR operators were specifically trained to both the anterior anatomical and the lateral ultrasound-guided approach. RESULTS: A total of 131 patients from 19 centres were enrolled and underwent 184 PSGBs. Patients were mainly male (83.2%) with a median age of 68 (63.8-69.2) years and a depressed left ventricular ejection fraction (25.0 ± 12.3%). The primary outcome was reached in 92% of patients, and the median reduction of arrhythmic episodes between 12 h before and after PSGB was 100% (interquartile range -100% to -92.3%). Arrhythmic episodes requiring treatment were significantly reduced comparing 12 h before the first PSGB with 12 h after the last procedure [six (3-15.8) vs. 0 (0-1), P < .0001] and comparing 1 h before with 1 h after each procedure [2 (0-6) vs. 0 (0-0), P < .001]. One major complication occurred (0.5%). CONCLUSIONS: The findings of this large, prospective, multicentre study provide evidence in favour of the effectiveness and safety of PSGB for the treatment of refractory ES.

Right Heart Adaptation to Exercise in Pulmonary Hypertension: An Invasive Hemodynamic Study.

BACKGROUND: Right heart failure (RHF) is associated with a dismal prognosis in patients with pulmonary hypertension (PH). Exercise right heart catheterization may unmask right heart maladaptation as a sign of RHF. We sought to (1) define the normal limits of right atrial pressure (RAP) increase during exercise; (2) describe the right heart adaptation to exercise in PH owing to heart failure with preserved ejection fraction (PH-HFpEF) and in pulmonary arterial hypertension (PAH); and (3) identify the factors associated with right heart maladaptation during exercise. METHODS AND RESULTS: We analyzed rest and exercise right heart catheterization from patients with PH-HFpEF and PAH. Right heart adaptation was described by absolute or cardiac output (CO)-normalized changes of RAP during exercise. Individuals with noncardiac dyspnea (NCD) served to define abnormal RAP responses (>97.5th percentile). Thirty patients with PH-HFpEF, 30 patients with PAH, and 21 patients with NCD were included. PH-HFpEF were older than PAH, with more cardiovascular comorbidities, and a higher prevalence of severe tricuspid regurgitation (P < .05). The upper limit of normal for peak RAP and RAP/CO slope in NCD were >12 mm Hg and ≥1.30 mm Hg/L/min, respectively. PH-HFpEF had higher peak RAP and RAP/CO slope than PAH (20 mm Hg [16-24 mm Hg] vs 12 mm Hg [9-19 mm Hg] and 3.47 mm Hg/L/min [2.02-6.19 mm Hg/L/min] vs 1.90 mm Hg/L/min [1.01-4.29 mm Hg/L/min], P < .05). A higher proportion of PH-HFpEF had RAP/CO slope and peak RAP above normal (P < .001). Estimated stressed blood volume at peak exercise was higher in PH-HFpEF than PAH (P < .05). In the whole PH cohort, the RAP/CO slope was associated with age, the rate of increase in estimated stressed blood volume during exercise, severe tricuspid regurgitation, and right atrial dilation. CONCLUSIONS: Patients with PH-HFpEF display a steeper increase of RAP during exercise than those with PAH. Preload-mediated mechanisms may play a role in the development of exercise-induced RHF.

Shedding Light on Latent Pulmonary Vascular Disease in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Among patients with heart failure with preserved ejection fraction (HFpEF), a distinct hemodynamic phenotype has been recently described, ie, latent pulmonary vascular disease (HFpEF-latentPVD), defined by exercise pulmonary vascular resistance (PVR) >1.74 WU. OBJECTIVES: This study aims to explore the pathophysiological significance of HFpEF-latentPVD. METHODS: The authors analyzed a cohort of patients who had undergone supine exercise right heart catheterization with cardiac output (CO) measured by direct Fick method, between 2016 and 2021. HFpEF-latentPVD patients were compared with HFpEF control patients. RESULTS: Out of 86 HFpEF patients, 21% qualified as having HFpEF-latentPVD, 78% of whom had PVR >2 WU at rest. Patients with HFpEF-latentPVD were older, with a higher pretest probability of HFpEF, and more frequently experienced atrial fibrillation and at least moderate tricuspid regurgitation (P < 0.05). PVR trajectories differed between HFpEF-latentPVD patients and HFpEF control patients (Pinteraction = 0.008), slightly increasing in the former and reducing in the latter. HFpEF-latentPVD patients displayed more frequent hemodynamically significant tricuspid regurgitation during exercise (P = 0.002) and had more impaired CO and stroke volume reserve (P < 0.05). Exercise PVR was correlated with mixed venous O2 tension (R2 = 0.33) and stroke volume (R2 = 0.31) in HFpEF-latentPVD patients. The HFpEF-latentPVD patients had had higher dead space ventilation during exercise and higher PaCO2 (P < 0.05), which correlated with resting PVR (R2 = 0.21). Event-free survival was reduced in HFpEF-latentPVD patients (P < 0.05). CONCLUSIONS: The results suggest that when CO is measured by direct Fick, few HFpEF patients have isolated latent PVD (ie, normal PVR at rest, becoming abnormal during exercise). HFpEF-latentPVD patients present with CO limitation to exercise, associated with dynamic tricuspid regurgitation, altered ventilatory control, and pulmonary vascular hyperreactivity, portending a poor prognosis.

Real-life experience with remdesivir for treatment of COVID-19 among older adults: a multicentre retrospective study.

INTRODUCTION: The effect of remdesivir on COVID-19 mortality remains conflicting. Elderly individuals are at risk for poor COVID-19 outcomes. We aimed to assess the effect of remdesivir on COVID-19 mortality among elderly individuals, using real-world data. METHODS: Retrospective multinational cohort of individuals aged ≥65 years, hospitalized with COVID-19 in six medical centres between January 2020 and May 2021. Associations with in-hospital mortality were evaluated using a multivariable logistic regression model with propensity score adjustment for remdesivir therapy and while implementing generalized estimating equations to control for centre effect. Sensitivity analysis was performed by stratification according to the degree of respiratory support. RESULTS: Of 3010 individuals included, 2788 individuals required either oxygen supplementation or non-invasive/invasive mechanical ventilation, 489 (16%) were treated with remdesivir, and 836 (28%) died. Median age was 77 (IQR 70-84) years and 42% were women. Remdesivir was the only therapeutic intervention associated with decreased mortality [adjusted OR (aOR) 0.49, 95% CI 0.37-0.66, P < 0.001]. This protective effect was shown for individuals requiring oxygen support and non-invasive mechanical ventilation, while no association was found among individuals necessitating invasive mechanical ventilation.Risk factors for mortality included invasive ventilation (aOR 5.18, 95% CI 2.46-10.91, P < 0.001), higher serum creatinine (aOR 1.25, 95% CI 1.09-1.43, P = 0.001) and dyspnoea (aOR 1.40, 95% CI 1.07-1.84, P = 0.015) on presentation, and other non-modifiable factors, such as comorbidities. CONCLUSIONS: Among elderly individuals hospitalized with COVID-19, remdesivir carries survival benefit for those with moderate to severe disease. Its role among individuals with critical illness should be further assessed.

Ablation of CTI-dependent flutter using different ablation technologies: acute and long-term outcome from the LEONARDO study.

BACKGROUND: A novel ablation catheter has been released to map and ablate the cavo-tricuspid isthmus (CTI) in patients with atrial flutter (AFL), improving ablation efficiency. METHODS: We evaluated the acute and long-term outcome of CTI ablation aiming at bidirectional conduction block (BDB) in a prospective, multicenter cohort study enrolling 500 patients indicated for typical AFL ablation. Patients were grouped on the basis of the AFL ablation method (linear anatomical approach, Conv group n = 425, or maximum voltage guided, MVG group, n = 75) and ablation catheter (mini-electrodes technology, MiFi group, n = 254, or a standard 8-mm ablation catheter, BLZ group, n = 246). RESULTS: Complete BDB according to both validation criteria (sequential detailed activation mapping or mapping only the ablation site) was achieved in 443 patients (88.6%). The number of RF applications needed to achieve BDB was lower in the MiFi MVG group vs both the MiFi Conv group and the BLZ Conv group (3.2 ± 2 vs 5.2 ± 4 vs 9.3 ± 5, p < 0.0001 for all comparisons). Fluoroscopy time was similar among groups, whereas we observed a reduction in the procedure duration from the BLZ Conv group (61.9 ± 26min) to the MiFi MVG group (50.6 ± 17min, p = 0.048). During a mean follow-up of 548 ± 304 days, 32 (6.2%) patients suffered an AFL recurrence. No differences were found according to BDB achieved by both validation criteria. CONCLUSIONS: Ablation was highly effective in achieving acute CTI BDB and long-term arrhythmia freedom irrespective of the ablation strategy or the validation criteria for CTI chosen by the operator. The use of an ablation catheter equipped with mini-electrodes technology seems to improve ablation efficiency. CLINICAL TRIAL REGISTRATION: Atrial Flutter Ablation in a Real World Population. (LEONARDO). CLINICALTRIALS: gov Identifier: NCT02591875.

Impact of severe secondary tricuspid regurgitation on rest and exercise hemodynamics of patients with heart failure and a preserved left ventricular ejection fraction.

Background: Both secondary tricuspid regurgitation (STR) and heart failure with preserved ejection fraction (HFpEF) are relevant public health problems in the elderly population, presenting with potential overlaps and sharing similar risk factors. However, the impact of severe STR on hemodynamics and cardiorespiratory adaptation to exercise in HFpEF remains to be clarified. Aim: To explore the impact of STR on exercise hemodynamics and cardiorespiratory adaptation in HFpEF. Methods: We analyzed invasive hemodynamics and gas-exchange data obtained at rest and during exercise from HFpEF patients with severe STR (HFpEF-STR), compared with 1:1 age-, sex-, and body mass index (BMI)- matched HFpEF patients with mild or no STR (HFpEF-controls). Results: Twelve HFpEF with atrial-STR (mean age 72 years, 92% females, BMI 28 Kg/m2) and 12 HFpEF-controls patients were analyzed. HFpEF-STR had higher (p < 0.01) right atrial pressure than HFpEF-controls both at rest (10 ± 1 vs. 5 ± 1 mmHg) and during exercise (23 ± 2 vs. 14 ± 2 mmHg). Despite higher pulmonary artery wedge pressure (PAWP) at rest in HFpEF-STR than in HFpEF-controls (17 ± 2 vs. 11 ± 2, p = 0.04), PAWP at peak exercise was no more different (28 ± 2 vs. 29 ± 2). Left ventricular transmural pressure and cardiac output (CO) increased less in HFpEF-STR than in HFpEF-controls (interaction p-value < 0.05). This latter was due to lower stroke volume (SV) values both at rest (48 ± 9 vs. 77 ± 9 mL, p < 0.05) and at peak exercise (54 ± 10 vs. 93 ± 10 mL, p < 0.05). Despite these differences, the two groups of patients laid on the same oxygen consumption isophlets because of the increased peripheral oxygen extraction in HFpEF-STR (p < 0.01). We found an inverse relationship between pulmonary vascular resistance and SV, both at rest and at peak exercise (R 2 = 0.12 and 0.19, respectively). Conclusions: Severe STR complicating HFpEF impairs SV and CO reserve, leading to pulmonary vascular de-recruitment and relative left heart underfilling, undermining the typical HFpEF pathophysiology.

Catheter Ablation for Atrial Fibrillation in Structural Heart Disease: A Review.

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Patients with structural heart disease (SHD) are at an increased risk of developing this arrhythmia and are particularly susceptible to the deleterious hemodynamic effects it carries. In the last two decades, catheter ablation (CA) has emerged as a valuable strategy for rhythm control and is currently part of the standard care for symptomatic relief in patients with AF. Growing evidence suggests that CA of AF may have potential benefits that extend beyond symptoms. In this review, we summarize the current knowledge of this intervention on SHD patients.

Role of CHA2DS2-VASc score in predicting atrial fibrillation recurrence in patients undergoing pulmonary vein isolation with cryoballoon ablation.

BACKGROUND: Pulmonary vein isolation by cryoablation (PVI-C) is a standard therapy for the treatment of atrial fibrillation (AF). The CHA2DS2-VASc score is a well-established predictor of AF-related stroke. Whether the CHA2DS2-VASc score can also be useful in predicting the long-term clinical outcomes following PVI-C is still unsettled. The aim of this analysis was to evaluate the role of the CHA2DS2-VASc score in predicting AF recurrence after PVI-C. METHODS: Patients with symptomatic AF underwent an index PVI-C. Data were collected prospectively in the framework of the 1STOP ClinicalService project. Patients were categorized into two groups: low risk (LR) and high risk (HR) based on CHA2DS2-VASc score (0-1 and ≥ 2, respectively). RESULTS: Out of 3313 patients, 1910 (57.6%) had a CHA2DS2-VASc score between 0 and 1, while 1403 (42.3%) had CHA2DS2-VASc > = 2. Patient characteristics were significantly different between the two cohorts, including age, sex, BMI, paroxysmal AF, history of stroke, diabetes, and ischemic cardiomyopathy. On the contrary, procedural times and acute complications were comparable. The 36-month freedom from AF after a single procedure was 72.5% (95% CI: 69.8-75.0) in the LR group and 65.9% (95% CI: 62.3-69.2) in the HR score group (HR: 1.26, 95% CI: 1.08-1.47, p = 0.001). After multivariate analysis, higher CHA2DS2-VASc score was still a significant predictor of the risk of AF recurrence (HR: 1.33; 1.10-1.60, p = 0.003). CONCLUSIONS: PVI-C is highly effective in the treatment of AF over the long term. A CHA2DS2-VASc score ≥ 2 is an independent predictor of AF recurrence during the follow-up and should be considered during the clinical management after the index procedure.

Predictors of survival in elderly patients with coronavirus disease 2019 admitted to the hospital: derivation and validation of the FLAMINCOV score.

OBJECTIVE: To identify predictors of 30-day survival in elderly patients with coronavirus disease 2019 (COVID-19). METHODS: Retrospective cohort study including patients with COVID-19 aged ≥65 years hospitalized in six European sites (January 2020 to May 2021). Data on demographics, comorbidities, clinical characteristics, and outcomes were collected. A predictive score (FLAMINCOV) was developed using logistic regression. Regression coefficients were used to calculate the score. External validation was performed in a cohort including elderly patients from a major COVID-19 centre in Israel. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) in the derivation and validation cohorts. Survival risk groups based on the score were derived and applied to the validation cohort. RESULTS: Among 3010 patients included in the derivation cohort, 30-day survival was 74.5% (2242/3010). The intensive care unit admission rate was 7.6% (228/3010). The model predicting survival included independent functional status (OR, 4.87; 95% CI, 3.93-6.03), a oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio of >235 (OR, 3.75; 95% CI, 3.04-4.63), a C-reactive protein level of <14 mg/dL (OR, 2.41; 95% CI, 1.91-3.04), a creatinine level of <1.3 (OR, 2.02; 95% CI, 1.62-2.52) mg/dL, and absence of fever (OR, 1.34; 95% CI, 1.09-1.66). The score was validated in 1174 patients. The FLAMINCOV score ranges from 0 to 15 and showed good discrimination in the derivation (AUC, 0.79; 95% CI, 0.77-0.81; p < 0.001) and validation cohorts (AUC, 0.79; 95% CI, 0.76-0.81; p < 0.001). Thirty-day survival ranged from 39.4% (203/515) to 95.3% (634/665) across four risk groups according to score quartiles in the derivation cohort. Similar proportions were observed in the validation set. DISCUSSION: The FLAMINCOV score identifying elderly with higher or lower chances of survival may allow better triage and management, including intensive care unit admission/exclusion.

Impact of thyroid function screening in a large cohort of patients admitted to an emergency department.

BACKGROUND: Thyroid dysfunctions are highly prevalent and can worsen underlying cardiopathies, but despite that the routine screening of thyroid function in the Emergency Department (ED) setting is not generally recommended. OBJECTIVE: To understand if staff training and implementation of rapid TSH screening (rTSH) could improve the management of patients arrived in the ED. Specifically, we aimed at evaluating the prevalence of undiagnosed thyroid diseases among ED patients; the effects of educational meetings in the clinical decision-making process; the usefulness of rTSH, in terms of variation of either the clinical work out or the existing treatment. DESIGN: Retrospective case-control study of 9227 patients managed in the ED of an academic institution. rTSH was routinely available for all patients, who were divided into rTSH-YES and rTSH-NO groups. RESULTS: We included 4243 and 4984  patients in the rTSH-YES and rTSH-NO group, respectively. Trained personnel uncovered a high prevalence of undiagnosed thyroid dysfunction (7%). The diagnosis in the ED of heart failure, history of thyroid diseases, contrast media/amiodarone administration and female gender were independently associated with an increased likelihood to have thyroid dysfunction. The rTSH improved the clinical outcome by (a) appropriate treatment of an underlying clinical condition causing ED entrance, (b) appropriate prophylaxis in patients requiring contrast media, (c) uncovering incorrect treatments, with 60% of patients on levothyroxine requiring a dose reduction. CONCLUSIONS: The rTSH in the ED revealed a high prevalence of untreated thyroid disorders with a major impact on following interventions. The training of a multidisciplinary team is crucial in driving the correct decision-making process.

Serum neurofilament light chain levels in Covid-19 patients without major neurological manifestations.

BACKGROUND: Increased serum levels of neurofilament light chain (sNFL), a biomarker of neuroaxonal damage, have been reported in patients with Covid-19. We aimed at investigating whether sNFL is increased in Covid-19 patients without major neurological manifestations, is associated with disease severity, respiratory and routine blood parameters, and changes longitudinally in the short term. METHODS: sNFL levels were measured with single molecule array (Simoa) technology in 57 hospitalized Covid-19 patients without major neurological manifestations and in 30 neurologically healthy controls. Patients were evaluated for PaO2/FiO2 ratio on arterial blood gas, Brescia Respiratory Covid Severity Scale (BRCSS), white blood cell counts, serum C-reactive protein (CRP), plasma D-dimer, plasma fibrinogen, and serum creatinine at admission. In 20 patients, NFL was also measured on serum samples obtained at a later timepoint during the hospital stay. RESULTS: Covid-19 patients had higher baseline sNFL levels compared to controls, regardless of disease severity. Baseline sNFL correlated with serum CRP and plasma D-dimer in patients with mild disease, but was not associated with measures of respiratory impairment. Longitudinal sNFL levels tended to be higher than baseline ones, albeit not significantly, and correlated with serum CRP and plasma D-dimer. The PaO2/FiO2 ratio was not associated with longitudinal sNFL, whereas BRCSS only correlated with longitudinal sNFL variation. CONCLUSIONS: We provide neurochemical evidence of subclinical axonal damage in Covid-19 also in the absence of major neurological manifestations. This is apparently not fully explained by hypoxic injury; rather, systemic inflammation might promote this damage. However, a direct neurotoxic effect of SARS-CoV-2 cannot be excluded.

Chronic Kidney Disease with Mild and Mild to Moderate Reduction in Renal Function and Long-Term Recurrences of Atrial Fibrillation after Pulmonary Vein Cryoballoon Ablation.

The aim of this research was to evaluate if patients with chronic kidney disease (CKD) and mild or mild to moderate depression of renal function have an increased risk of atrial fibrillation (AF) recurrences after cryoballoon (CB) ablation. We performed a retrospective analysis of AF patients undergoing pulmonary vein isolation (PVI) by CB. The cohort was divided according to the KDIGO CKD-EPI classification into a (1) normal, (2) mildly decreased, or (3) mild to moderate reduction in estimated glomerular filtration rate (eGFR). Freedom from AF recurrences was the primary endpoint. A total of 1971 patients were included (60 ± 10 years, 29.0% females, 73.6% paroxysmal AF) in the study. Acute success and complication rates were 99.2% and 3.7%, respectively, with no significant differences among the three groups. After a follow-up of 24 months, AF recurrences were higher in the mildly and mild to moderate CKD groups compared to the normal kidney function group (23.4% vs. 28.3% vs. 33.5%, p < 0.05). Mild to moderate CKD was an independent predictor of AF recurrences after the blanking period (hazard ratio:1.38, 95% CI 1.02−1.86, p = 0.037). In conclusion, a multicenter analysis of AF patients treated with cryoablation revealed mild to moderate reductions in renal functions were associated with a higher risk of AF recurrences. Conversely, the procedural success and complication rates were similar in patients with normal, mildly reduced, or mild to moderate reduction in eGFR.

Second versus fourth generation of cryoballoon catheters: The 1STOP real-world multicenter experience.

BACKGROUND: It has been observed that the fourth-generation cryoballoon (CB4) ablation catheter increased the rate of acute real-time recordings of pulmonary vein isolation (PVI) during the ablation for the treatment of atrial fibrillation (AF). The aim of this analysis was to compare the long-term outcome results between patients treated with the CB4 and second-generation cryoballoon (CB2). METHODS: In total, 492 patients suffering from AF, underwent PVI ablation with either the CB2 or CB4 catheter within this examination of the 1STOP real-world Italian project and were included in the analysis. Specifically, 246 consecutive patients treated by CB4 were compared to 246 propensity-matched control patients who underwent PVI using CB2. RESULTS: When comparing the patient cohorts treated with CB2 versus CB4, acute success rate (99.6 ± 4.7% vs. 99.7 ± 3.6%, p = .949) and peri-procedural complications (3.7% vs.1.2%, p = .080) were similar in both groups, respectively. However, procedure time (100 vs.75 min, p < .001) and fluoroscopy duration (21 vs.17 min, p < .001) were all significantly lower in the CB4 treated patient cohort. At the 12-month follow-up, the freedom from AF recurrence after a 90-day blanking period was significant higher in the CB4 as compared with the CB2 group (93.3% vs.81.3%, p < .001). CONCLUSIONS: In summary, usage of the CB4 ablation catheter increased the rate of acute PVI recording capability and resulted in a higher rate of long-term PVI success, as demonstrated by the reduced rate of AF recurrence in comparison to the CB2 cohort at the 12-month follow-up period.

Lead Abandonment and Subcutaneous Implantable Cardioverter-Defibrillator (S-ICD) Implantation in a Cohort of Patients With ICD Lead Malfunction.

Background: When an implantable-cardioverter defibrillator (ICD) lead becomes non-functional, a recommendation currently exists for either lead abandonment or removal. Lead abandonment and subcutaneous ICD (S-ICD) implantation may represent an additional option for patients who do not require pacing. The aim of this study was to investigate the outcomes of a strategy of lead abandonment and S-ICD implantation in the setting of lead malfunction. Methods: We analyzed all consecutive patients who underwent S-ICD implantation after abandonment of malfunctioning leads and compared their outcomes with those of patients who underwent extraction and subsequent reimplantation of a single-chamber transvenous ICD (T-ICD). Results: Forty-three patients underwent S-ICD implantation after abandonment of malfunctioning leads, while 62 patients underwent extraction and subsequent reimplantation of a new T-ICD. The two groups were comparable. In the extraction group, no major complications occurred during extraction, while the procedure failed and an S-ICD was implanted in 4 patients. During a median follow-up of 21 months, 3 major complications or deaths occurred in the S-ICD group and 11 in the T-ICD group (HR 1.07; 95% CI 0.29-3.94; P = 0.912). Minor complications were 4 in the S-ICD group and 5 in the T-ICD group (HR 2.13; 95% CI 0.49-9.24; P = 0.238). Conclusions: In the event of ICD lead malfunction, extraction avoids the potential long-term risks of abandoned leads. Nonetheless the strategy of lead abandonment and S-ICD implantation was feasible and safe, with no significant increase in adverse outcomes, and may represent an option in selected clinical settings. Further studies are needed to fully understand the potential risks of lead abandonment. Clinical Trial Registration: URL: ClinicalTrials.gov Identifier: NCT02275637.

Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy.

BACKGROUND: Vitamin D deficiency has been suggested to favor a poorer outcome of Coronavirus disease-19 (COVID-19). We aimed to assess if 25-hydroxyvitamin-D (25OHD) levels are associated with interleukin 6 (IL-6) levels and with disease severity and mortality in COVID-19. METHODS: We prospectively studied 103 in-patients admitted to a Northern-Italian hospital (age 66.1 ± 14.1 years, 70 males) for severely-symptomatic COVID-19. Fifty-two subjects with SARS-CoV-2 infection but mild COVID-19 symptoms (mildly-symptomatic COVID-19 patients) and 206 subjects without SARS-CoV-2 infection were controls. We measured 25OHD and IL-6 levels at admission and focused on respiratory outcome during hospitalization. RESULTS: Severely-symptomatic COVID-19 patients had lower 25OHD levels (18.2 ± 11.4 ng/mL) than mildly-symptomatic COVID-19 patients and non-SARS-CoV-2-infected controls (30.3 ± 8.5 ng/mL and 25.4 ± 9.4 ng/mL, respectively, p < 0.0001 for both comparisons). 25OHD and IL-6 levels were respectively lower and higher in severely-symptomatic COVID-19 patients admitted to intensive care Unit [(ICU), 14.4 ± 8.6 ng/mL and 43.0 (19.0-56.0) pg/mL, respectively], than in those not requiring ICU admission [22.4 ± 1.4 ng/mL, p = 0.0001 and 16.0 (8.0-32.0) pg/mL, p = 0.0002, respectively]. Similar differences were found when comparing COVID-19 patients who died in hospital [13.2 ± 6.4 ng/mL and 45.0 (28.0-99.0) pg/mL] with survivors [19.3 ± 12.0 ng/mL, p = 0.035 and 21.0 (10.5-45.9) pg/mL, p = 0.018, respectively). 25OHD levels inversely correlated with: i) IL-6 levels (ρ - 0.284, p = 0.004); ii) the subsequent need of the ICU admission [relative risk, RR 0.99, 95% confidence interval (95%CI) 0.98-1.00, p = 0.011] regardless of age, gender, presence of at least 1 comorbidity among obesity, diabetes, arterial hypertension, creatinine, IL-6 and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count; iii) mortality (RR 0.97, 95%CI, 0.95-0.99, p = 0.011) regardless of age, gender, presence of diabetes, IL-6 and C-reactive protein and lactate dehydrogenase levels, neutrophil cells, lymphocytes and platelets count. CONCLUSION: In our COVID-19 patients, low 25OHD levels were inversely correlated with high IL-6 levels and were independent predictors of COVID-19 severity and mortality.

Current Limitations of Invasive Exercise Hemodynamics for the Diagnosis of Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Exercise hemodynamics can differentiate heart failure with preserved ejection fraction (HFpEF) from noncardiac dyspnea. However, respiratory pressure swings may impact hemodynamic measurements, potentially leading to misdiagnosis of HFpEF. Moreover, threshold values for abnormal hemodynamic response indicative of HFpEF are not universally accepted. Thus, we sought to evaluate the impact of respiratory pressure swings on hemodynamic data interpretation as well as the concordance among 3 proposed exercise hemodynamic criteria for HFpEF: (1) end-expiratory pulmonary artery wedge pressure (PAWPexp) ≥25 mm Hg; (2) PAWPexp/cardiac output slope >2 mm Hg/L per minute; and (3) respiratory-averaged (avg) mean pulmonary artery pressure >30 mm Hg, total pulmonary resistanceavg >3 WU, PAWPavg ≥20 mm Hg. METHODS: Fifty-seven patients with unexplained dyspnea (70% women, 70±9 years) underwent exercise cardiac catheterization. The difference between end-expiratory and averaged hemodynamic values, as well as the concordance among the 3 hemodynamic definitions of HFpEF, were assessed. RESULTS: End-expiratory hemodynamics measurements were higher than values averaged across the respiratory cycle. During exercise, a larger proportion of patients exceeded the threshold of 25 mm Hg for PAWPexp rather than for PAWPavg (70% versus 53%, P<0.01). The concordance of 3/3 HFpEF exercise hemodynamic criteria was recorded in 70% of patients. PAWPexp/cardiac output slope identified HFpEF more frequently than the other 2 criteria (81% versus 64% to 69%), incorporating over 97% of abnormal responses to the latter. Patients with 3/3 positive criteria had worse clinical, gas-exchange, and hemodynamic profiles. CONCLUSIONS: Respiratory pressure swings impact on the exercise hemodynamic definitions of HFpEF that provide discordant results in 30% of patients. Equivocal diagnoses of HFpEF might be limited by adopting the most sensitive and inclusive criterion alone (ie, PAWPexp/cardiac output slope).

Impact of COVID-19 on exercise pathophysiology: a combined cardiopulmonary and echocardiographic exercise study.

Survivors from COVID-19 pneumonia can present with persisting multisystem involvement (lung, pulmonary vessels, heart, muscle, red blood cells) that may negatively affect exercise capacity. We sought to determine the extent and the determinants of exercise limitation in patients with COVID-19 at the time of hospital discharge. Eighteen consecutive patients with COVID-19 and 1:1 age-, sex-, and body mass index-matched controls underwent: spirometry, echocardiography, cardiopulmonary exercise test and exercise echocardiography for the study of pulmonary circulation. Arterial blood was sampled at rest and during exercise in patients with COVID-19. Patients with COVID-19 lie roughly on the same oxygen consumption isophlets than controls both at rest and during submaximal exercise, thanks to supernormal cardiac output (P < 0.05). Oxygen consumption at peak exercise was reduced by 30% in COVID-19 (P < 0.001), due to a peripheral extraction limit. In addition, within COVID-19 patients, hemoglobin content was associated with peak oxygen consumption (R2 = 0.46, P = 0.002). Respiratory reserve was not exhausted (median [IRQ], 0.59 [0.15]) in spite of moderate reduction of forced vital capacity (79 ± 40%). Pulmonary artery pressure increase during exercise was not different between patients and controls. Ventilatory equivalents for carbon dioxide were higher in patients with COVID-19 than in controls (39.5 [8.5] vs. 29.5 [8.8], P < 0.001), and such an increase was mainly explained by increased chemosensitivity. When recovering from COVID-19, patients present with reduced exercise capacity and augmented exercise hyperventilation. Peripheral factors, including anemia and reduced oxygen extraction by peripheral muscles were the major determinants of deranged exercise physiology. Pulmonary vascular function seemed unaffected, despite restrictive lung changes.NEW & NOTEWORTHY At the time of hospital discharge, patients with COVID-19 present with reduced functional capacity and exercise hyperventilation. Peripheral factors, namely reduced oxygen extraction (myopathy) and anemia, which are not fully compensated by a supernormal cardiac output response, account for exercise limitation before exhaustion of the respiratory reserve. Enhanced chemoreflex sensitivity, rather increased dead space, mainly accounts for exercise hyperventilation. The pulmonary vascular response to exercise circulation of survived patients with COVID-19 does not present major pathological changes.

The spectrum of thyroid function tests during hospitalization for SARS COV-2 infection.

OBJECTIVE: Alterations in thyroid function tests (TFTs) have been recorded during SARS-CoV-2 infection as associated to either a destructive thyroiditis or a non-thyroidal illness. METHODS: We studied 144 consecutive COVID-19 patients admitted to a single center in intensive or subintensive care units. Those with previous thyroid dysfunctions or taking interfering drugs were excluded. Differently from previous reports, TSH, FT3, FT4, thyroglobulin (Tg), anti-Tg autoantibodies (TgAb) were measured at baseline and every 3-7 days. C-reacting protein (CRP), cortisol and IL-6 were also assayed. RESULTS: The majority of patients had a normal TSH at admission, usually with normal FT4 and FT3. Low TSH levels were found either at admission or during hospitalization in 39% of patients, associated with low FT3 in half of the cases. FT4 and Tg levels were normal, and TgAb-negative. TSH and FT3 were invariably restored at the time of discharge in survivors, whereas were permanently low in most deceased cases, but only FT3 levels were predictors of mortality. Cortisol, CRP and IL-6 levels were higher in patients with low TSH and FT3 levels. CONCLUSIONS: Almost half of our COVID-19 patients without interfering drugs had normal TFTs both at admission and during follow-up. In this series, the transient finding of low TSH with normal FT4 and low FT3 levels, inversely correlated with CRP, cortisol and IL-6 and associated with normal Tg levels, is likely due to the cytokine storm induced by SARS-Cov-2 with a direct or mediated impact on TSH secretion and deiodinase activity, and likely not to a destructive thyroiditis.

Is 40 Joules Enough to Successfully Defibrillate With Subcutaneous Implantable Cardioverter-Defibrillators?

OBJECTIVES: This study evaluated the efficacy of conversion test performed at 40 J (defibrillation margin ≥40 J), and factors potentially associated with test failure were identified. BACKGROUND: Current subcutaneous implantable cardioverter-defibrillator (S-ICD) devices deliver a maximum of 80 J. Functional defibrillation testing is recommended at S-ICD implantation, and it is usually conducted by delivering a shock energy of 65 J to ensure a safety defibrillation margin ≥15 J. Although high rates of successful conversion were reported at 65 J, limited data exist on the defibrillation margin extent. METHODS: Ventricular fibrillation was induced and conversion test was performed by delivering a 40-J shock in 308 patients. Success was defined as termination of ventricular fibrillation by the first shock delivered in standard polarity. The S-ICD system positioning was evaluated with the PRAETORIAN score using bidirectional chest X-rays. RESULTS: The generator was positioned in an intermuscular pocket in 301 patients (98%) and the lead was implanted by means of a 2-incision technique. The PRAETORIAN score was <90 (low risk of conversion failure) in 293 (95%) patients. Overall, ventricular fibrillation termination occurred in 259 (84%) patients with 40 J. Male gender (odds ratio [OR]: 3.79; 95% confidence interval [CI]: 1.09 to 13.14; p = 0.036), body mass index (OR: 1.09; 95% CI: 1.01 to 1.19; p = 0.036), dilated cardiomyopathy with reduced ejection fraction (OR: 0.42; 95% CI: 0.20 to 0.87; p = 0.019), and PRAETORIAN score >50 (OR: 2.93; 95% CI: 1.26 to 6.83; p = 0.013) were independently associated with conversion failure. CONCLUSIONS: The authors showed a high rate of defibrillation success with 40-J shocks in S-ICD systems implanted by means of modern surgical techniques. The variables associated with shock failure were male gender, higher body mass index, and suboptimal device position according to the PRAETORIAN score.