Relationship between hyponatremia at hospital admission and cardiopulmonary profile at follow-up in patients with SARS-CoV-2 (COVID-19) infection.

PURPOSE: Hyponatremia occurs in about 30% of patients with pneumonia, including those with SARS-CoV-2 (COVID-19) infection. Hyponatremia predicts a worse outcome in several pathologic conditions and in COVID-19 has been associated with a higher risk of non-invasive ventilation, ICU transfer and death. The main objective of this study was to determine whether early hyponatremia is also a predictor of long-term sequelae at follow-up. METHODS: In this observational study, we collected 6-month follow-up data from 189 laboratory-confirmed COVID-19 patients previously admitted to a University Hospital. About 25% of the patients (n = 47) had hyponatremia at the time of hospital admission. RESULTS: Serum [Na+] was significantly increased in the whole group of 189 patients at 6 months, compared to the value at hospital admission (141.4 ± 2.2 vs 137 ± 3.5 mEq/L, p < 0.001). In addition, IL-6 levels decreased and the PaO2/FiO2 increased. Accordingly, pulmonary involvement, evaluated at the chest X-ray by the RALE score, decreased. However, in patients with hyponatremia at hospital admission, higher levels of LDH, fibrinogen, troponin T and NT-ProBNP were detected at follow-up, compared to patients with normonatremia at admission. In addition, hyponatremia at admission was associated with worse echocardiography parameters related to right ventricular function, together with a higher RALE score. CONCLUSION: These results suggest that early hyponatremia in COVID-19 patients is associated with the presence of laboratory and imaging parameters indicating a greater pulmonary and right-sided heart involvement at follow-up.

Tenosynovial complications identify TTR cardiac amyloidosis among patients with hypertrophic cardiomyopathy phenotype.

Recent evidence suggests that carpal tunnel syndrome (CTS) and brachial biceps tendon rupture (BBTR) represent red flags for ATTR cardiac amyloidosis (ATTR-CA). The prevalence of upper limb tenosynovial complications in conditions entering differential diagnosis with CA, such as HCM or Anderson-Fabry disease (AFD), and hence their predictive accuracy in this setting, still remains unresolved. OBJECTIVE: To investigate the prevalence of CTS and BBTR in a consecutive cohort of ATTR-CA patients, compared with patients with HCM or AFD and with individuals without cardiac disease history. PARTICIPANTS: Consecutive patients with a diagnosis of ATTR-CA, HCM and AFD were evaluated. A control group of consecutive patients was recruited among subjects hospitalized for noncardiac reasons and no cardiac disease history. The presence of BBTR, CTS or prior surgery related to these conditions was ascertained. RESULTS: 342 patients were prospectively enrolled, including 168 ATTR-CA (141 ATTRwt, 27 ATTRm), 81 with HCM/AFD (N = 72 and 9, respectively) and 93 controls. CTS was present in 75% ATTR-CA patients, compared with 13% and 10% of HCM/AFD and controls (P = 0.0001 for both comparisons). Bilateral CTS was present in 60% of ATTR-CA patients, while it was rare (2%) in the other groups. BBTR was present in 44% of ATTR-CA patients, 8% of controls and 1% in HCM/AFD. CONCLUSIONS: CTS and BBTR are fivefold more prevalent in ATTR-CA patients compared with cardiac patients with other hypertrophic phenotypes. Positive predictive accuracy for ATTR-CA is highest when involvement is bilateral. Upper limb assessment of patients with HCM phenotypes is a simple and effective way to raise suspicion of ATTR-CA.

Gene expression profiling reveals GC and CEACAM1 as new tools in the diagnosis of lung carcinoids.

BACKGROUND: Classification of lung carcinoids into typical and atypical is a diagnostic challenge since no immunohistochemical tools are available to support pathologists in distinguishing between the two subtypes. A differential diagnosis is essential for clinicians to correctly discuss therapy, prognosis and follow-up with patients. Indeed, the distinction between the two typical and atypical subtypes on biopsies/cytological specimens is still unfeasible and sometimes limited also after radical surgeries. By comparing the gene expression profile of typical (TC) and atypical carcinoids (AC), we intended to find genes specifically expressed in one of the two subtypes that could be used as diagnostic markers. METHODS: Expression profiling, with Affymetrix arrays, was performed on six typical and seven atypical samples. Data were validated on an independent cohort of 29 tumours, by means of quantitative PCR and immunohistochemistry (IHC). RESULTS: High-throughput gene expression profiling was successfully used to identify a gene signature specific for atypical lung carcinoids. Among the 273 upregulated genes in the atypical vs typical subtype, GC (vitamin D-binding protein) and CEACAM1 (carcinoembryonic antigen family member) emerged as potent diagnostic markers. Quantitative PCR and IHC on a validation set of 17 ACs and 12 TCs confirmed their reproducibility and feasibility. CONCLUSIONS: GC and CEACAM1 can distinguish between TC and AC, defining an IHC assay potentially useful for routine cytological and histochemical diagnostic procedures. The high sensitivity and reproducibility of this new diagnostic algorithm strongly support a further validation on a wider sample size.

Candidacy and long-term outcomes of subcutaneous implantable cardioverter-defibrillators in current practice in patients with hypertrophic cardiomyopathy.

BACKGROUND: In patients with Hypertrophic Cardiomyopathy (HCM) S-ICD is usually the preferred option as pacing is generally not indicated. However, limited data are available on its current practice adoption and long-term follow-up. METHODS: Consecutive HCM patients with S-ICD implanted between 2013 and 2021 in 3 international centers were enrolled in this observational study. Baseline, procedural and follow-up data were regularly collected. Efficacy and safety were compared with a cohort of HCM patients implanted with a tv-ICD. RESULTS: Seventy patients (64% males) were implanted with S-ICD at 41 ± 15 years, whereas 168 patients with tv-ICD at 49 ± 16 years. For S-ICD patients, mean ESC SCD risk score was 4,5 ± 1.9%: 25 (40%) at low-risk, 17 (27%) at intermediate and 20 (33%) at high-risk. Patients were followed-up for 5.1 ± 2.3 years. Two patients (0.6 per 100-person-years, vs 0.4 per 100 person-years with tv-ICD, p = 0.45) received an appropriate shock on VF, 17 (24%) were diagnosed with de-novo AF. Inappropriate shocks occurred in 4 patients (1.2 per 100-person-years, vs 0.9 per 100 person-years with tv-ICD, p = 0.74), all before Smart-Pass algorithm implementation. Four patients experienced device-related adverse events (1.2 per 100-person-years, vs 1 per 100 person-years with tv-ICD, p = 0.35%). CONCLUSIONS: S-ICDs were often implanted in patients with an overall low-intermediate ESC SCD risk, reflecting both the inclusion of additional risk markers and a lower decision threshold. S-ICDs in HCM patients followed for over 5 years showed to be effective in conversion of VF and safe. Greater scrutiny may be required to avoid overtreatment in patients with milder risk profiles.

Clinical profile and outcome of cardiomyopathies in infants and children seen at a tertiary centre.

INTRODUCTION: Due to their rare prevalence and marked heterogeneity, pediatric cardiomyopathies (CMPs) are little known and scarcely reported. We report the etiology, clinical profile and outcome of a consecutive cohort of children diagnosed with CMP and followed at Meyer Children's Hospital over a decade. PATIENTS AND METHODS: We retrospectively reviewed patients consecutively referred from May 2008 to May 2019 for pediatric onset CMP (<18 years). Heart disease caused by arrhythmic disorders, toxic agents, rheumatic conditions and maternal disease were excluded. RESULTS: We enrolled 110 patients (65 males), diagnosed at a median age of 27 [4-134] months; 35% had an infant onset (<1 year of age). A positive family history was more often associated with childhood-onset (38.8%). Hypertrophic cardiomyopathy (HCM; 48 patients) was the most frequent phenotype, followed by dilated cardiomyopathy (DCM; 35 patients). While metabolic and idiopathic etiologies were preponderant in infants, metabolic and sarcomeric diseases were most frequent in the childhood-onset group. Major adverse cardiac events (MACE) occurred in 31.8% of patients, including hospitalization for acute heart failure in 25.5% of patients, most commonly due to DCM. Overall, the most severe outcomes were documented in patients with metabolic diseases. CONCLUSIONS: In a consecutive cohort of pediatric patients with CMP, those with infantile onset and with a metabolic etiology had the worst prognosis. Overall, MACE occurred in 41% of the entire population, most commonly associated with DCM, inborn errors of metabolism and genetic syndromes. Systematic NGS genetic testing was critical for etiological diagnosis and management.

Should temozolomide be used on the basis of O6-methylguanine DNA methyltransferase status in patients with advanced neuroendocrine tumors? A systematic review and meta-analysis.

BACKGROUND: Temozolomide (TEM) is an active treatment in metastatic neuroendocrine tumors (NETs). Patients affected by glioblastoma multiforme or advanced melanoma treated with TEM who have deficiency of O6-methylguanine DNA methyltransferase (MGMT) have a better responses and survival. However, the predictive role of MGMT in patients with NETs treated with TEM is still debated. METHODS: We conducted a systematic review of the literature and meta-analysis, based on PRISMA methodology, searching in the main databases (PubMed, Embase, Scopus, Web of Science, Cochrane Library and clinical trial.gov) and the proceedings of the main international congresses, until April 26, 2021. RESULTS: Twelve out of 616 articles were selected for our analysis, regarding a total of 858 NET patients treated with TEM-based chemotherapy. The status of MGMT had been tested in 513 (60%) patients, using various methods. The pooled overall response rate (ORR) was higher in MGMT-deficient compared with MGMT-proficient NETs, with a risk difference of 0.31 (95% confidence interval, CI: 0.13-0.50; p < 0.001; I2: 73%) and risk ratio of 2.29 (95% CI: 1.34-3.91; p < 0.001; I2: 55%). The pooled progression free survival (PFS) (hazard ratio, HR = 0.56; 95% CI: 0.43-0.74; p < 0.001) and overall survival (OS) (HR = 0.41; 95% CI: 0.20-0.62; p = 0.011) were longer in MGMT-deficient versus MGMT-proficient NETs. CONCLUSIONS: Our meta-analysis suggested that MGMT status may be predictive of TEM efficacy. However, due to the high heterogeneity of the evaluated studies the risk of biases should be considered. On this hypothesis future homogeneous prospective studies are warranted.

The association between rhabdomyolysis and acute renal failure in patients undergoing cardiopulmonary bypass.

OBJECTIVE: The authors describe 9 cases of rhabdomyolytic acute renal failure (ARF) as a complication of cardiopulmonary bypass. EXPERIMENTAL DESIGN: Retrospective research between June 1992 and March 1994. SETTING: Department of Cardiac Surgery. PATIENTS: 931 consecutive patients undergoing major cardiac surgery. INTERVENTIONS: Patients affected by rhabdomyolytic ARF were treated with pharmacological therapy and/or plasmapheresis/continuous arteriovenous hemofiltration. In seven patients indirect cannulation of the femoral artery was used. MEASURES: Incidence, risk factors of syndrome results obtained with pharmacological treatment, CAVH and plasmapheresis were evaluated. Statistical analysis was performed with ANOVA, Tukey Kramer test and chi2 test (p<0.05 as significant). RESULTS: The syndrome occurred in 0.96% (9/931 patients) of the total cases; 11.3% (6/53 -p<0.0000) in patients undergoing a direct femoral artery cannulation for cardiopulmonary bypass and 9.5% (2/21, p<0.01) in patients in which the aortic balloon pump was used. Six patients develop acute anuric renal failure and underwent plasma exchange and hemodialysis (1 case) or CAVH (5 cases); 3 patients underwent early medical treatment and developed developed acute renal failure (ARF) with preserved diuresis. Early medical therapy appeared to prevent the evolution towards anuric ARF. The indirect cannulation of the femoral artery does not seem to produce a rhabdomyolytic ARF syndrome. In patients with direct femoral artery cannulation risk factors appear to be: arteriopathy (p<0.001), prolonged extra corporeal circulation (p<0.001), low cardiac output syndrome (p<0.001), continuous i.v. infusion of epinephrine (p<0.0001). CONCLUSIONS: Rhabdomyolytic acute renal failure is a severe complication, early identification of patients ¿at risk¿ is most important. The preventive measures and the therapy adopted proved efficient.

[Predictive value of the shunt-to-infarct size ratio as a surgical risk factor in patients with decompensated post-ischemic interventricular septal rupture]. / Valore dell'indice di Shunt/DPos come previsione di rischio chirurgico nelle rotture post-ischemiche scompensate del setto interventricolare.

Postischemic septal rupture has always been evaluated, in respect of surgical indication, as regards the time lapse between infarct and rupture, interval between rupture and operation, extension of myocardial damage and general risk factors such as age, sex and associated pathologies. But in fact the surgeon is dealing with a two sided problem, the MI and the rupture, and thus surgical results depend upon both the residual ventricular function after MI and the consequences of volume overload on a damaged muscle. Surgical indication could not be based on a single criterion only. Extension of the MI alone is not fully predictive of operative mortality because, aside the reperfusion injury, the repair further jeopardizes viable myocardium and alters ventricular geometry; although the shunt appears unrelated to mortality it certainly interferes with operative outcome at least because of the time elapsed between rupture and repair. So far an index which could correlate the extension of myocardial damage and the entity of the shunt with each other was not available. Patients with septal rupture follow an emergency protocol and are often insufficiently investigated but every patients has a least one echo-Doppler evaluation or even a ventriculography while one or more ECGs are always available. With the presumption that the Qp/Qs is roughly indicative of the right ventricular volume overload and that ecg signs of myocardial infarct are always reliable, we have reviewed among our 24 patients with septal rupture those where a full ecg tracing and a quantitative Echo or angiographic evaluation of the shunt were available.(ABSTRACT TRUNCATED AT 250 WORDS)

Ten years of surgery of aortic dissections and aneurysms. Clinical experience and original contributions.

From January '82 to April '91, 117 patients with aortic disease were operated upon at our University Hospital in Genoa, Italy. Thirty-seven had arch dissections or aneurysms; 66 had acute aortic dissection type A and 14 had aortic dissections or aneurysms type B, acute and chronic. Patients with arch or type B aortic pathology but without surgical indication and cases of post-traumatic aortic transections are not included. There were 84 male and 33 female patients with a mean age of 52 (6 min and 74 max). In the acute patients, the mean interval between clinical onset and surgery was 34 hours (6 min-72 max). All patients with primary arch disease had surgical repair with the aid of deep hypothermia and circulatory arrest (17-96 min). Type A dissections were treated with standard CPBP at 28 degrees C. Surgical techniques included direct suture of intimal tear alone, direct suturing of the two aortic stumps; interposition of Dacron tubular prosthesis; Bentall repair; separated valve and aortic replacement; an original aortic bulb aortoplasty with valve repair; arch replacement with resuturing of one or more aortic trunks. Human fibrin glue (Tissucol) was employed either as haemostatic agent, widely spread over the suture lines or as tissue adhesion agent between dissected aortic layers. Human fibrin glue is adopted because it gathers high glueing capacity and maintenance of the elastic property of the vessel wall. Hospital mortality (30 days) has been 25% in ascending aortic dissections (16/66 patients) and 50% in patients with arch disease (18/37 patients) who needed circulatory arrest. Late mortality 5/83 (6%). Reoperations for aortic valve insufficiency or re-dissection have been 7 (8.4%). Early diagnosis (increasing reliability of 2D-Echo and CT scans), aggressive surgery, meticulous myocardial and cerebral protection and introduction in clinical use of biological glues seem to be the milestones of present and further improvements in surgical results.