Low- vs high-dose ARNI effects on clinical status, exercise performance and cardiac function in real-life HFrEF patients.

PURPOSE: Only a few studies are available on dose-related effects of sacubitril/valsartan (angiotensin receptor neprilysin inhibition (ARNI)) in real-life patients with heart failure and reduced ejection fraction (HFrEF). We sought to investigate clinical and functional effects in real-life HFrEF patients receiving ARNI at a different cumulative dose. METHODS: This was an observational study in consecutive outpatients admitted for HFrEF from October 2017 to June 2019. The PARADIGM criteria were needed for enrolment. ARNI was uptitrated according to blood pressure, drug tolerability, renal function and kaliemia. At least 10-month follow-up was required in each patient. Clinical assessment, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-min walk test and strain echocardiography were performed in each patient on a regular basis during the observational period. At the end of the study, patients were divided into two groups based on the median yearly dose of the ARNI medication. RESULTS: A total of 90 patients, 64 ± 11 years, 82% males, were enrolled. The cut-off dose was established in 75 mg BID, and the study population was divided into group A (≤ 75 mg), 52 patients (58%), and group B (> 75 mg), 38 patients (42%). The follow-up duration was 12 months (range 11-13). NYHA class, KCCQ score and 6MWT performance ameliorated in both groups, with a quicker time to benefit in group B. The proportion of patients walking > 350 m increased from 21 to 58% in group A (p < 0.001), and from 29 to 82% in group B (p < 0.001). A positive effect was also disclosed in the left ventricular remodelling, strain deformation and diastolic function. CONCLUSION: One-year ARNI treatment was effective in our real-life HFrEF patient population, leading to clinical and functional improvement in both study groups, slightly greater and with a shorter time to benefit in group B.

Diagnostic and prognostic role of electrocardiogram in acute myocarditis: A comprehensive review.

BACKGROUND: Acute myocarditis represents a challenging diagnosis as there is no pathognomonic clinical presentation. In patients with myocarditis, electrocardiogram (ECG) can display a variety of non-specific abnormalities. Nevertheless, ECG is widely used as an initial screening tool for myocarditis. METHODS: We researched all possible ECG alterations during acute myocarditis evaluating prevalence, physiopathology, correlation with clinical presentation patterns, role in differential diagnosis, and prognostic yield. RESULTS: The most common ECG abnormality in myocarditis is sinus tachycardia associated with nonspecific ST/T-wave changes. The presence of PR segment depression both in precordial and limb leads, a PR segment depression in leads with ST segment elevation, a PR segment elevation in aVR lead or a ST elevation with pericarditis pattern favor generally diagnosis of perimyocarditis rather than myocardial infarction. In patients with acute myocarditis, features associated with a poorer prognosis are: pathological Q wave, wide QRS complex, QRS/T angle ≥ 100°, prolonged QT interval, high-degree atrioventricular block and malignant ventricular tachyarrhythmia. On the contrary, ST elevation with a typical early repolarization pattern is associated with a better prognosis. CONCLUSIONS: ECG alterations in acute myocarditis could be very useful in clinical practice for a patient-tailored approach in order to decide appropriate therapy, length of hospitalization, and frequency of followup.

Prevention of post-operative hyperalgesia in a heroin-addicted patient on methadone maintenance.

WHAT IS KNOWN AND OBJECTIVE: The exponential increase in chronic opioid consumers resulted in more challenges regarding post-operative pain management. Considering the usual hyperalgesic response to pain and the increased opioid-tolerance, a multidrug approach should be desirable. CASE DESCRIPTION: We described the strategy in pain management of a patient receiving methadone maintenance treatment, who underwent surgery associated with moderate post-operative pain. The combination of balanced general anaesthesia and intraoperative continuous low-dose infusion of ketamine assured an appropriate control of post-operative pain without increasing opioid consumption. Besides, it was not associated with psychomimetic effects. WHAT IS NEW AND CONCLUSION: Ketamine can effectively reduce opioid requirements in chronic opioid users on methadone maintenance therapy and should therefore be considered promptly as part of a multimodal perioperative analgesia management in this category of patients.

Intramyocardial calcification in apical hypertrophic cardiomyopathy assessed using multimodality imaging: a case series.

Apical hypertrophic cardiomyopathy (ApHCM) is an HCM variant, affecting frequently males in midlife. It is characterized by apical obliteration and persistent diastolic contraction, often resulting in microvascular ischaemia. We report five cases of ApHCM, with evidence of intramyocardial calcification on echocardiogram. On cardiac magnetic imaging (MRI), a hypointense component at early gadolinium enhancement (EGE) sequences, compatible with calcium, and a deep layer, with hyperintensity at late gadolinium enhancement (LGE) sequences, referable to fibrosis, suggest an endomyocardial fibrosis (EMF) diagnosis. EMF pathologic hallmark is endocardium and myocardium scarring, evolving to dystrophic calcification. It is found only in few ApHCM patients. Our series is the largest one described until now. Analysing patients' history, coexistent inflammatory triggers were evident in all of them, so their co-morbidities could represent a further cause of small vessel disease, in the context of ischaemic microvascular stress due to hypertrophy, leading to fibrosis and dystrophic calcification. This series could demonstrate the relation between apical fibrosis/calcification and microvascular ischaemia due to hypertrophy and inflammatory triggers.

The Long-Term Benefit of Sacubitril/Valsartan in Patients with HFrEF: A 5-Year Follow-Up Study in a Real World Population.

Heart failure (HF) is a progressive condition with an increasing prevalence, and the scientific evidence of heart failure with reduced ejection fraction (HFrEF) reports a 6% rate of 1-year mortality in stable patients, whereas, in recently hospitalized patients, the 1-year mortality rates exceed 20%. The Sacubitril/Valsartan (S/V), the first angiotensin receptor neprilysin inhibitor (ARNI), significantly reduced both HF hospitalization and cardiovascular mortality. AIM OF THE STUDY: to evaluate the effect of S/V in a follow-up period of 5 years from the beginning of the therapy. We compared the one-year outcomes of S/V use with those obtained after 5 years of therapy, monitoring the long-term effects in a real-world population with HFrEF. METHODS: Seventy consecutive patients with HFrEF and eligible for ARNI, according to PARADIGM-HF criteria, were enrolled. All patients had an overall follow-up of 60 months, during which time they underwent standard transthoracic echocardiography (TTE) with Global Longitudinal Strain (GLS) evaluation, the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Six Minutes Walking Test (6MWT), and blood tests (NT-pro-BNP and BNP, renal function tests). RESULTS: NTproBNP values were reduced significantly among the three time-points (p < 0.001). Among echocardiographic parameters, left ventricle end-diastolic volume (LV EDV) and E/e' significantly were reduced at the first evaluation (12 months), while left ventricle end-systolic volume (LV ESV) decreased during all follow-ups (p < 0.001). LV EF (p < 0.001) and GLS (p < 0.001) significantly increased at both evaluations. The 6MWT (p < 0.001) and KCCQ scores (p < 0.001) increased significantly in the first 12 months and remained stable along the other time-points. NYHA class showed an increase in class 1 subjects and a decrease in class 3 subjects during follow-up. NTproBNP, BNP, 6MWT, and KCCQ scores showed a significant change in the first 12 months, while LVEF, GLS, and ESV changed during all evaluations. CONCLUSIONS: We verified that the improvements obtained after one year of therapy had not reached a plateau phase but continued to improve and were statistically significant at 5 years. Although our data should be confirmed in larger and multicentre studies, we can state that the utilization of Sacubitril/Valsartan has catalysed substantial transformations in the prognostic landscape of chronic HFrEF, yielding profound clinical implications.

Diagnosis of type 2 Brugada pattern: insights from a pilot survey.

BACKGROUND: Differentiation of Type 2 Brugada Pattern (BP) from incomplete right bundle branch block or normal rSr' pattern can be insidious. The aim of this study was to assess interobserver and intraobserver agreement in the diagnosis of type 2 BP in a cohort of cardiologists with different skills. METHODS: We collected 14 ECGs with a positive terminal deflection of the QRS complex in lead V1 and V2 at the 4th intercostal space. We proposed these ECGs, specifying to use 2012 Consensus conference criteria for diagnosis of type 2 BP, to 42 participants: 14 arrhythmologists, 14 general cardiologists and 14 electrophysiology (EP) fellows. The same 14 ECGs, with a different order, were proposed fifteen days later to the same cohort to assess intraobserver variability. Authors analyzed all 14 ECGs in order to assess whether 2012 Consensus Conference criteria for BP were fulfilled. All patients underwent provocative test with IC antiarrhythmics drugs (flecainide) in order to exclude or confirm the diagnosis of Brugada Syndrome (BrS). RESULTS: Slight interobserver agreement (Fleiss K<0.20) in the diagnosis of type 2 BP was observed in all three categories of cardiologists. Considering five operators per class, intraobserver agreement is variable (k ranging from 0.000 to 0.857), with a slight superiority of arrhytmologists (k minimum value 0.276; k maximum value 0.857). CONCLUSIONS: This study demonstrated, for the first time, a low interobserver agreement in diagnosis of type 2 BP in categories of cardiologists with different abilities. Reproducibility of type 2 BP diagnosis (intraobserver agreement) is poor, even among experts. These findings highlight the difficulties in analysis of ECG with BrS suspicion and, therefore, underscore the key role of clinical and anamnestic data.

Old and New Drugs for Treatment of Advanced Heart Failure.

BACKGROUND: Advanced heart failure (HF) is a progressive disease with high mortality and limited medical therapeutic options. Long-term mechanical circulatory support and heart transplantation remain goldstandard treatments for these patients; however, access to these therapies is limited by the advanced age and multiple comorbidities of affected patients, as well as by the limited number of organs available. METHODS: Traditional and new drugs available for the treatment of advanced HF have been researched. RESULTS: To date, the cornerstone for the treatment of patients with advanced HF remains water restriction, intravenous loop diuretic therapy and inotropic support. However, many patients with advanced HF experience loop diuretics resistance and alternative therapeutic strategies to overcome this problem have been developed, including sequential nephron blockade or use of the hypertonic saline solution in combination with high-doses of furosemide. As classic inotropes augment myocardial oxygen consumption, new promising drugs have been introduced, including levosimendan, istaroxime and omecamtiv mecarbil. However, pharmacological agents still remain mainly short-term or palliative options in patients with acute decompensation or excluded from mechanical therapy. CONCLUSION: Traditional drugs, especially when administered in combination, and new medicaments represent important therapeutic options in advanced HF. However, their impact on prognosis remains unclear. Large trials are necessary to clarify their therapeutic potential and prognostic role in these fragile patients.

Facial pain: a possible therapy with stellate ganglion block.

OBJECTIVE: The goal of the present study is to verify the efficacy of stellate ganglion block (SGB) in the treatment of facial pain that can be found in different pathological syndromes, and also to examine whether the efficacy is dependent upon when this therapy is administered. PATIENTS: Fifty patients (divided into two randomized groups) with facial pain caused by traumas, iatrogenic issues, herpes zoster, or neurological pathologies participated in this study. DESIGN AND INTERVENTIONS: The first group (N = 25) was treated with SGB produced by 10 administrations of 10 mg of levobupivacaine given every other day, followed by one administration per month for 6 months thereafter. The second group was treated with the drugs tramadol 100 mg/day and gabapentin 1800 mg/day orally for 6 months; during the 7th month they were given SGB therapy using the same methodology as that described for the first group. RESULTS: Before treatment, the mean visual analog scale (VAS) pain score for the first group was 8.89; after the 10th block treatment it was just 0.2, and it remained at that reduced level for the 6th and 12th months. Before treatment, the mean VAS pain score for the second group was 8.83; after the 20th day on medication it was reduced to 4.1, after 6 months it was 5.7 and after 12 months it was 4.9. CONCLUSIONS: Our results indicate that patients must be treated with SGB therapy precociously to receive its full benefits.

Postoperative management of elective esophagectomy for cancer.

Postoperative management after elective esophagectomy for cancer has not been standardized. Thoracoabdominal incision with associated pain, extended operative time with consequent extracellular fluid shifts, single lung ventilation, potential for prolonged postoperative mechanical ventilation and comorbidities in patients with esophageal cancer, all contribute to high perioperative risk. Respiratory problems remain the major cause of both mortality and morbidity after esophagectomy for cancer. A specific pulmonary disorder, acute respiratory distress syndrome (ARDS) occurs in 10-20% of patients after esophagectomy. ARDS mortality exceeds 50%. Atrial fibrillation, that complicates recovery in 20 to 25% of patients after esophagectomy, contributes to make outcome worse. Anesthesiologists should adopt strategies known to be able to optimize patient outcome. Decreased postoperative mortality and morbidity have been associated with epidural analgesia, bronchoscopy to clear persistent bronchial secretions, intraoperative fluid restriction and early extubation. It has been shown that setting up early respiratory physiotherapy and mobilitation may improve functional recovery.