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.

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.

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.

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.

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.

Rhabdomyolytic acute renal failure in cardiac surgery. A clinical case.

OBJECTIVE: Authors describe 1 case of rhabdomyolytic acute renal failure as a complication of Cardiopulmonary bypass. EXPERIMENTAL DESIGN: Case report. SETTING: Department of Cardiac Surgery. INTERVENTIONS: Patient affected by rhabdomyolytic acute renal failure was treated with pharmacological therapy, plasmapheresis and continuous arteriovenous hemofiltration (CAVH). RESULTS: Anuric acute renal failure was diagnosed in 2nd post surgical day; serum myoglobin values was 16000 micrograms/l (normal values in non surgical patients < 88 micrograms/l), creatine phosphokinase serum values was 8790 UI/L (with Mb fraction < 8%). Patient underwent CAVH and two a day sessions of plasmapheresis; hematochemical and hemodynamic parameters improved progressively with resolution of acute renal failure and resumption of the diuresis on the 10th day. The CAVH was suspended on the 11th day and plasmapheresis on the 5th. Rhabdomyolytic syndrome should be correlated to the direct cannulation of the femoral artery for cardiopulmonary bypass and to prolonged time of extracorporeal circulation, with consequent leg ischemia/reperfusion induced injury which occurs during the extracorporeal circulation and continued during postoperative period; contributory causes should be the low cardiac output syndrome and alpha vasoconstrictor effect of high dose continuous intravenous administration of epinephrine. CONCLUSIONS: Rhabdomyolytic acute renal failure is a severe complication of cardiopulmonary bypass; plasmapheresis and continuous arteriovenous hemofiltration seems to be suitable treatments.

[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)

[Comparison between low and high doses of aprotinin in heart surgery]. / Confronto tra bassi ed alti dosaggi di aprotinina in cardiochirurgia.

High dose aprotinin has been used in cardiac surgery (Royston 1987) to reduce post operative bleeding. A low dose aprotinin ie 2000000 KIU in the oxygenator prime, has been also proposed. OBJECTIVE. To evaluate postoperative losses and holomogous blood transfusions, in patients undergoing cardiac surgery treated with low and high dose aprotinin. METHODS AND MATERIALS. Ninety-nine patients, between January and May 1993, have randomized in 3 groups: A, high dose aprotinin; B, low dose aprotinin; C, control. All patients were treated with additional blood saving techniques routinely used in our center. Statistical analysis was performed by means of ANOVA and Tukey Kramer test. MAIN RESULTS. Five patients (3 in group A, 1 each in groups B and C) have been excluded during the trial. The groups resulted omogeneus and comparable. Total blood losses were 372 +/- 159 ml in group A, 401 +/- 178 ml in group B (difference are not significative); the 621 +/- 255 m1 in group C are highly significative. Patients transfused were 18.7% in group C, 10.34% in group A and 6.20% in group B. CONCLUSIONS. Effects of low dose aprotinin are comparable to high dose. Further advantages with low dose are reduction of collateral effects and intolerance phenomena and a better cost benefits ratio.

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.

Evaluation of an enzymatic method for fast identification of Listeria spp. in cheese and meat products.

Listeria-Tek ELISA was compared with conventional cultural procedure of FIL/IDF (Federation International de Laiterie/International Dairy Federation) modified by us. The ELISA assay is able to detect Listeria innocua, Listeria monocytogenes, Listeria murrayi and Listeria welshimeri, after 48 h in artificially contaminated cheeses. No specific reactions, no false positive or negative were detected and the assay has a high correlation with the conventional method used in this research. We also analyzed meat products and cheeses and identified Listeria spp. and Listeria monocytogenes serotypes. In 313 food samples examined there were only 3 false positives. With ELISA Kit we obtained 0.9% more than with the cultural method and the percentage of false positives is 1.6%. So in commercial products the total absence of false negatives demonstrates the great sensitivity of the method in respect to investigated microorganisms. As determined by cultures 218 samples contained 47 Listeriae monocytogenes, 67 Listeriae innocua, 21 Listeriae welshimeri, 7 Listeriae ivanovii, 3 Listeriae murrayi and 3 Listeriae denitrificans. Listeria monocytogenens includes serotypes 1 (13) and serotypes 4 (14). 20 Listeriae monocytogenes were serotyped by polyantisera Difco (Detroit, Michigan).

[Methylprednisolone sodium succinate in the profile of respiratory complications after thoracic surgical intervention]. / Il metilprednisolone sodio succinato nella profilassi delle complicanze respiratorie dopo interventi di chirurgia toracica.

Methylprednisolone sodium succinate (MPSS) was compared in a randomized double blind study to placebo in the prevention of respiratory complications in 40 patients submitted to thoracic surgery. The results indicate that the patients who received MPSS showed a lower incidence of respiratory complications, adverse reactions, chest pain and metabolic acidosis.

[Hemodynamic classification of acute myocardial infarction: physiopathological aspects and prognostic implications. Considerations on 130 cases (author's transl)]. / L'inquadramento emodinamico dell'infarto miocardico in fase acuta: aspetti fisiopatologici e implicazioni prognostiche. Indagine su 130 casi.

Hemodynamic evaluations of 130 patients with acute myocardial infarction were performed by right and/or left heart catheterization. 115 patients were subdivided in six groups by the pulmonary artery mean pressure (PMP)-left ventricular stroke work index (LVSWI) relationship: 1) normal LVSWI in relation to PMP (14.8% of all cases); 2) increased LVSWI in relation to PMP (0.9%); 3) moderately reduced LVSWI with increased PMP (severe heart failure-cardiogenic shock) (7.0%); 5) reduced LVSWI with low or normal PMP (22.6%); 6) normal LVSWI with elevated PMP (reduced left ventricular compliance or high pulmonary vascular resistance) (15.7%). 28 cases were studied by right and left heart catheterization; in 10 cases only left heart catheterization was performed. Discriminant analysis on the values measured at the first stage of hemodynamic monitoring was conducted: this type of mathematical analysis seemed to provide a more useful prognostic index.

[Left ventricular microcatheterization during acute myocardial infarction (author's transl)]. / Il microcateterismo del ventricolo sinistro in corso di infarto miocardico in fase acuta

Left ventricular microcatheterization at the bedside was accomplished in 20 acutely ill patients with myocardial infarction. Direct measure of the left ventricular end-diastolic pressure shows that its values can substantially differ from those of the pulmonary artery end-diastolic pressure. The authors observed that left ventricular microcatheterization is indicated, in the course of acute myocardial infarction, in the following circumstances: --when either the pulmonary artery end-diastolic or the pulmonary capillary pressure is beyond normal limits; --in the presence of tachyarrhythmias which, for alteration of the dynamics of atrial contraction, increase the difference between the left ventricular and pulmonary artery end-diastolic pressures; --when a mitralic defect is associated with the acute myocardial infarction.