The BrAID study protocol: integration of machine learning and transcriptomics for brugada syndrome recognition.

BACKGROUND: Type 1 Brugada syndrome (BrS) is a hereditary arrhythmogenic disease showing peculiar electrocardiographic (ECG) patterns, characterized by ST-segment elevation in the right precordial leads, and risk of Sudden Cardiac Death (SCD). Furthermore, although various ECG patterns are described in the literature, different individual ECG may show high-grade variability, making the diagnosis problematic. The study aims to develop an innovative system for an accurate diagnosis of Type 1 BrS based on ECG pattern recognition by Machine Learning (ML) models and blood markers analysis trough transcriptomic techniques. METHODS: The study is structured in 3 parts: (a) a retrospective study, with the first cohort of 300 anonymized ECG obtained in already diagnosed Type 1 BrS (75 spontaneous, 150 suspected) and 75 from control patients, which will be processed by ML analysis for pattern recognition; (b) a prospective study, with a cohort of 11 patients with spontaneous Type 1 BrS, 11 with drug-induced Type 1 BrS, 11 suspected BrS but negative to Na + channel blockers administration, and 11 controls, enrolled for ECG ML analysis and blood collection for transcriptomics and microvesicles analysis; (c) a validation study, with the third cohort of 100 patients (35 spontaneous and 35 drug-induced BrS, 30 controls) for ML algorithm and biomarkers testing. DISCUSSION: The BrAID system will help clinicians improve the diagnosis of Type 1 BrS by using multiple information, reducing the time between ECG recording and final diagnosis, integrating clinical, biochemical and ECG information thus favoring a more effective use of available resources. Trial registration Clinical Trial.gov, NCT04641585. Registered 17 November 2020, https://clinicaltrials.gov/ct2/show/NCT04641585.

Role of dipyridamole-echocardiography test in the evaluation of coronary reserve after coronary artery bypass grafting.

The object of this study was to assess the usefulness of the dipyridamole-echocardiography test in the early evaluation of coronary artery bypass grafting, when the use of an exercise stress test is precluded. We studied 39 consecutive patients (37 men and two women, mean age 57.3 years) referred to our institute for elective coronary artery bypass. Five patients had single, 12 patients double, 20 patients triple vessel disease, and two had left main stem disease. Nineteen left internal mammary artery grafts, 20 sequential grafts, and 39 single vein grafts were performed. All the patients were subjected to the test before (time range 1 to 3 days) and after (time range 6 to 10 days) the operation in the absence of therapy. Dipyridamole was administered intravenously 0.56 mg/kg over 4 minutes (low dose); if no effect was apparent, an additional 0.28 mg/kg over 2 minutes (high dose) was given. During the test, blood pressure and a twelve-lead electrocardiogram were monitored. An arbitrary wall motion score was derived by dividing the left ventricle into six regions and grading from 0 to 3-normokinetic, hypokinetic, akinetic, and dyskinetic zones. Preoperatively the test was positive in 38 patients as evidenced by wall motion abnormalities (36 patients had electrocardiographic changes) and in one patient by electrocardiographic changes and chest pain; 22 tests were positive after the low dose and 17 after the high dose. Angina was present in 33 patients. Mean wall motion score was 1.64 per patient in the basal condition and 4.03 per patient after the test (p less than 0.001). After coronary bypass in three patients the test was positive at the same dosage that was used preoperatively, as shown by wall motion abnormalities (in two patients by electrocardiographic changes, as well). Four patients had symptoms. Furthermore, at 6 months' follow-up, a treadmill stress test performed in these three patients was positive for ischemia and angina. The wall motion score was 1.25 per patient in the basal condition and 1.53 per patient after the test (no significant difference). When the preoperative wall motion score obtained after dipyridamole echocardiography was compared with the postoperative score, a statistically significant difference was seen: 4.03 per patient versus 1.53 per patient (p less than 001). In eight patients we observed an improvement of basal myocardial contractility after the operation, which indicates the reversibility of wall motion abnormalities observed before coronary bypass. In conclusion our data show that the dipyridamole-echocardiography test is a suitable method for the early assessment of bypass grafting when other methods, exercise dependent, are not indicated.(ABSTRACT TRUNCATED AT 400 WORDS)

Characterization of myocardial tissue in patients undergoing maintenance hemodialysis by quantitative echocardiography.

The uremic state affects myocardial structure, bringing about, among other things, interstitial calcium deposition. Abnormalities of myocardial structure can be assessed quantitatively and noninvasively during life by the analysis of the gray-level distribution of conventional two-dimensional echocardiograms. The aim of this study was to evaluate the role of quantitative echocardiography in providing information on myocardial structure in patients under maintenance hemodialysis and to relate the ultrasonic findings with abnormalities in calcium-phosphate metabolism. Forty patients undergoing dialysis without abnormalities in left ventricular regional and global function and 17 hypertensive patients with comparable left ventricular hypertrophy were studied. The distribution of the gray levels within a region of interest in the interventricular septum was analyzed off-line by an array processor-based computer. Compared with hypertensive patients, patients undergoing dialysis showed a greater myocardial echogenicity (mean 92 +/- 20 versus 72 +/- 15; p = 0.004) and a reduced homogeneity of distribution of gray levels (entropy 4.5 +/- 0.2 versus 4.2 +/- 0.2, p < 0.01; uniformity 0.010 +/- 0.003 versus 0.020 +/- 0.004, p < 0.005). In the same patients, a significant negative linear relation was found between entropy and calcium-phosphate product (r = -0.66; p = 0.001). Quantitative analysis of conventional two-dimensional echocardiograms allows the detection of a pathologic myocardial structure in patients under maintenance hemodialysis with normal left ventricular function. These abnormalities are related to disorders of calcium-phosphate metabolism and bear no relationship to the degree of left ventricular hypertrophy.

Prognostic value of ventricular arrhythmias and transient ST-T changes after myocardial infarction: a two-year follow-up with ambulatory ECG recording.

The aim of this study is to evaluate the frequency and prognostic significance of ventricular arrhythmias (VA) and of ST-T changes found during 24-h ECG recording in patients who survived an acute myocardial infarction. Eighty-nine patients (2 females and 87 males) discharged from hospital after acute myocardial infarction were studied. Mean age was 52.2 years (SD +/- 10) with a range of 26-68. Serial observations were carried out at 1, 2, 3, 6, and 12 months after the acute event. Eight patients died during the first two years of follow-up, of these, 2 deaths were of noncardiac origin: one was due to gastric carcinoma and the other to pulmonary neoplasm. Of the 6 cardiac deaths, 4 were sudden and unexpected and 2 were due to reinfarction. Statistical analysis of the results obtained in the first three months of follow-up has not shown any significant correlation between pathologic patterns and cardiac death. In the second period we found a statistically significant relationship between cardiac death and multiform VPBs (p less than 0.05), CVA (p less than 0.05), and ST-T changes (p less than 0.05). More significant was the correlation between cardiac death and the presence at the same time of ST-T changes and multiform VPBs (p less than 0.01).

Histologic evidence of myocardial damage in apparently healthy subjects with ventricular arrhythmias and myocardial dysfunction.

The association of ventricular arrhythmias and myocardial dysfunction could be considered an early step toward cardiomyopathy; therefore, we studied 28 patients in NYHA class I and II, characterized by complex ventricular arrhythmias (VA) on 24-h Holter monitoring and volumetric and/or contractile abnormalities on a standard two-dimensional echocardiogram (2-D echo). All patients underwent radioisotopic angiography, 20 patients complete hemodynamic study, and 15 patients endomyocardial biopsy. Ambulatory ECG monitoring showed the presence of frequent premature ventricular contractions in 14 patients (50%) and episodes of ventricular tachycardia in 16 patients (57%). 2-D echo showed mono- or biventricular enlargement and dyssynergies in 25 patients (89%) (left ventricle in 6, right ventricle in 11, both in 8). Two patients showed only left ventricle enlargement and one patient isolated left ventricular dyssynergies. Radioisotopic angiography showed mono- or biventricular ejection fraction reduction in 24 patients (85%) and regional dyssynergies in 24 patients (85%) in accordance with 2-D echo. Hemodynamic study showed in all patients normal coronary arteries, and right and left angiography confirmed enlargement and/or regional dyssynergies. Endomyocardial biopsy was abnormal in 11 of 15 patients: various degrees of hypertrophy, parcellar fibrosis, and adipogenic infiltration were found. Our preliminary data suggest that the simultaneous occurrence of ventricular arrhythmias and ventricular dyssynergies and/or enlargement in patients without apparent clinical heart disease may represent an early stage of dilated cardiomyopathy.

Suitability of Doppler echocardiography for the assessment of right heart hemodynamics after De Vega tricuspid annuloplasty.

Cardiac Doppler Echocardiography is a suitable method for to evaluating right heart hemodynamics. However, the surgical correction of tricuspid valve annuloplasty changes valve geometry and might possibly lead to a technical obstacle to this estimation. The accuracy of Doppler echocardiography in the assessment of tricuspid regurgitation and systolic pulmonary pressure in patients who had undergone De Vega annuloplasty was evaluated in this study. Ten patients (9 females and 1 male), mean age 55.7 +/- 7.8 years, who had a previous De Vega annuloplasty for the treatment of tricuspid regurgitation due to a severe mitral stenosis, underwent a Doppler echocardiography study and, within two hours, right heart catheterization for a direct comparison of parameters calculated by different methods. Right ventricular-atrial maximal pressure gradient was found to be 32.6 +/- 11.07 mmHg by Doppler and 31.4 +/- 11.07 mmHg by catheterization. Pulmonary systolic pressure was 42.6 +/- 9.1 mmHg at Doppler and 39.1 +/- 11.3 mmHg at catheterization, with a highly significant correlation between the 2 techniques (r = 0.98%, p < 0.01). With semiquantitative Doppler evaluation 10 patients showed tricuspid insufficiency, which was mild in 8 and medium in 2. At catheterization all patients were found to have mild tricuspid insufficiency. Cardiac Doppler seems a reliable method in the evaluation of tricuspid regurgitation and of pulmonary systolic pressure even in patients who underwent De Vega annuloplasty.

Non-invasive monitoring of hemodynamic parameters during hemodialysis.

We studied in 13 hemodialysis patients intradialytic variations of blood volume (BV) and cardiac output, by means of non-invasive methods. We found a weak correlation, r 0.2 or less, between BV variations and intradialysis blood pressure variations. The sensitivity of the former in describing the variations of the latter was only 32%. During the 30 min preceeding the hypothensive crisis the percent BV variations did not show any predictive trend. On the contrary, refilling increased as blood pressure dropped and a weak inverse relation (r -0.35) was found between these two parameters. Unstable patients had predialytic blood volume values significantly lower than stable ones and comparable to healthy subjects. On the contrary, the correlation between percent variations of cardiac output index and MAP was 0.68 with a sensitivity and specificity of 90% and 59%, respectively. Unfortunately these promising results were obtained only with an estimate of cardiac output obtained by echocardiography and not by transthoracic impedance cardiography, which is much more feasible than the former as on-line monitoring of cardiac output. On-line monitoring of hemodynamic parameters is an appealing but still unsolved task.

Thermal balance and dialysis hypotension.

Many studies have confirmed our original observation that dialysate T set at about 35 degrees C affords a better hemodynamic protection than the standard dialysate T of 37-38 degrees C. In this review we present some new data on the hemodynamic mechanism of the protective effect of cold dialysis on blood pressure. The study was based on serial assessment of the percent changes occurring during dialysis treatment in estimated stroke volume (aortic blood flow determined by Doppler echocardiography), blood volume (hemoglobinometry), arterial pressure (Dynamap), and heart rate (ECG), from which cardiac output (CO) indexes and total peripheral vascular resistances (TPVR) were derived. Of the 14 pts studied, 7 showed a drop in mean arterial pressure (MAP) of 25% or greater during standard dialysis (unstable patients). Compared with the 7 patients having more stable intradialysis MAP, unstable pts showed greater reduction in CO which was disproportionately greater than the reduction in blood volume, and a paradoxical decrease in TPVR, the difference being highly significant (p < 0.01 for both changes). When crossed-over to cold dialysis, along with a significantly lower reduction in MAP (p < 0.01) the unstable pts showed a lower decrease in CO which paralleled the reduction in blood volume, and an increase in TPVR. These changes were highly significant (p < 0.01). Data suggest that dialysis hypotension is characterized by an impaired venous return, probably due to the peripheral blood pooling (increased ratio between the 'unstressed' and 'stressed' blood volume) associated with the decrease in TPVR. Exposure of extracorporeal blood to cold dialysate favours the venous return to the heart by increasing TPVR and the 'stressed' blood volume.

Age dependency of myocardial structure: a quantitative two-dimensional echocardiographic study in a normal population.

Histological changes of the myocardium occur with aging due to an increase in collagen content, hypertrophy of fibers, and patchy fibrosis. Quantitative analysis of conventional echocardiographic images provides an in vivo assessment of myocardial structure by the evaluation of the gray level distribution; with this technique, a relation between myocardial fibrosis and pathological ultrasonic response has been documented. The aim of this study was to evaluate the relation between ultrasonically assessed myocardial structure and age in a normal population. Seventy-eight subjects (47 men; mean age, 51 years; age range, 23-87 years) without apparent cardiovascular and systemic disease underwent conventional two-dimensional echocardiographic examinations. Still frames at end-diastole from apical four-chamber view were digitized and converted in matrices of 256 x 256 pixels. First-order statistical analysis was performed to describe a region of interest in the interventricular septum. The following parameters were studied: mean (gray level amplitude), standard deviation (overall contrast), uniformity (tonal organization), and entropy (tendency of gray levels to be spread). Myocardial structure was assessed in 75 of 78 subjects, divided into three groups: I, age 23-40 years; II, age 41-65 years; and III, > 65 years. Significant differences for all the parameters were found between the age groups. Age correlated directly with mean and entropy (r = 0.77 and 0.69, respectively) and inversely with uniformity (r = 0.70). Our results suggest that quantitative echocardiography can reveal age-related changes in myocardial structure that are characterized by a greater echogenicity and loss in tonal organization, possibly due to increased collagen content within the fibers.

Ambulatory follow-up of aortic dissection: comparison between computed tomography and biplane transesophageal echocardiography.

UNLABELLED: Aim of the study was to assess the relative usefulness of transesophageal echocardiography (TEE) and X-ray computed tomography (CT) in the follow-up of patients who survived an aortic dissection. MATERIALS AND METHODS: We evaluated 44 patients (age = 57 +/- 12 years) with treated aortic dissection: 14 had a De Bakey type I, 20 a type II and 1 patient a type III dissection treated surgically: 1 patient had a type I, 1 a type II and 7 a type III dissection treated medically. All entered an outpatient follow-up program with serial evaluations at 1, 6 and 12 months after initial diagnosis by dual noninvasive imaging protocol. A contrast-enhanced CT scan and a TEE with biplane probe were performed on the same day and in random order. RESULTS: A total of 252 evaluations with both CT and TEE were considered. A completely normal study was found in 45 TEE and 48 CT evaluations. The following abnormal findings could be documented by one or both techniques: thrombus in the false lumen (TEE: n = 48; CT: n = 45 evaluations); intimal flap (TEE and CT: n = 68); aortic dilatation (TEE and CT: n = 15); pericardial effusion (TEE and CT: n = 3); aortic pseudoaneurysm (TEE: n = 2; CT: n = 3); isthmic coarctation (TEE and CT: n = 1). Regarding the presence or absence of these abnormalities, which are within the diagnostic domain of both imaging techniques, the results were fully concordant in 245 studies, and discordant in 7, with an overall agreement of 97%. In addition, some abnormal findings could be detected by TEE only: aortic insufficiency (n = 36); intimal tear (n = 25); spontaneous echocontrast effect in the false lumen (n = 39 evaluations). Other abnormal findings could be detected by CT only: a pleural effusion in 4, a truncus anonymous dissection in 1, a pseudoaneurysm due to suture dehiscence of the distal anastomosis of the ascending aorta in 1 evaluation (which yielded ambiguous results by TEE, with turbulent flow departing from the graft). CONCLUSION: Both CT and TEE are atraumatic, safe and accurate techniques for serial follow-up imaging of patients treated for aortic dissection. Information provided by CT is largely redundant, rather than additive, to that provided by TEE. The latter should be probably preferred for shorter imaging time, accuracy and convenience, although CT might still play a role in selected cases of ambiguous TEE results.

Prognostic value of the dipyridamole echocardiography test performed early after aortocoronary bypass surgery.

It has been demonstrated that high dose (up to 0.84 mg/kg over 10 min) dipyridamole echocardiography stress testing is feasible even in the first few hours after coronary artery bypass graft surgery and can be used to assess the beneficial physiological effects of coronary revascularization as well as graft patency. The aim of this study was to assess the role of dipyridamole echocardiography testing performed shortly after myocardial revascularization in the stratification of prognosis during follow-up. We studied 49 consecutive patients (45 males and 4 females; mean age 56 +/- 8 years) referred to our institute for elective myocardial revascularization. Six patients had single, 14 double, and 29 triple vessel disease. Forty-two left internal mammary artery grafts, 16 sequential venous grafts, and 45 single venous grafts were performed. All patients were submitted to dipyridamole echocardiography testing before (range 1-3 days) and shortly after (range 5-7 days) myocardial revascularization, always with the patients off antianginal medication. An arbitrary wall-motion score grading from 0 to 3 (normal, hypokinesia, akinesia, and dyskinesia) was applied to the seven regions into which the left ventricle was divided. Before surgery 48 patients showed wall-motion abnormalities during the test (47 patients also presented ECG changes). Angina occurred in 48 patients. One patient had ischemic ECG changes and angina. The mean wall-motion score was 3.11 per patient before and 6.5 per patient after the test (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Ambulatory electrocardiography in the screening of patients with palpitations]. / L'elettrocardiografia dinamica nello screening del paziente con palpitazioni.

The role of 24 hour Holter monitoring in the screening of patients complaining of palpitations is reviewed. The term "palpitations", although not always unequivocally used, implies the presence of an arrhythmia. The clinical-instrumental correlation of an intermittent symptom is made possible by continuous electrocardiographic monitoring. Answers to be expected from a 24 hour Holter monitoring in order to achieve an early characterization of the arrhythmia are related to: site of origin, incidence, circadian distribution, prognostic stratification, events aggregation, presence of other asymptomatic abnormalities (rhythm, ST-T).

Impaired sympathetic response before intradialytic hypotension: a study based on spectral analysis of heart rate and pressure variability.

The purpose of this study was to evaluate the autonomic response to standard haemodialysis and the changes associated with the onset of intradialytic hypotension in 12 normotensive patients with uraemia. Power spectra of R-R interval and of blood pressure fluctuations were obtained during a standard dialysis session and estimated in the low-frequency (LF, 30-150 mHz) and high-frequency (HF, 150-400 mHz) range. The absolute power of the LF component of blood pressure variations and the LF/HF ratio of R-R interval were assumed as indexes of sympathetic activity. Standard haemodialysis induced hypotension in six patients (unstable) while a minor pressure decline was present in the other six (stable). Normalized blood volume before dialysis and percentage volume reduction were similar in the two groups. Tachycardia in response to pressure and volume decrease was more pronounced in stable than in unstable patients, as evidenced by a higher slope of the relation between R-R interval and systolic blood pressure (7.9 versus 0.9 ms/mmHg, P<0.01). Sympathetic tone was enhanced during early dialysis in all patients (+2+/-1 for R-R LF/HF ratio, +2.4+/-0.6 mmHg2 and +7.2+/-2 mmHg2 for absolute LF power of diastolic and of systolic blood pressure respectively, P<0.05), compared with baseline predialysis values. During late dialysis, unstable patients showed an impairment of sympathetic activation which preceded hypotension and was maximal during the crisis (-2.9+/-1.4 for R-R LF/HF ratio, -2.7+/-1.4 mmHg2 and -8.6+/-4.0 mmHg2 for absolute LF power of diastolic and of systolic blood pressure respectively, P<0.05). On the contrary, stable patients showed constantly elevated indexes (+3.7+/-1.4 for R-R LF/HF ratio, +5.9+/-2.7 mmHg2 and +13.3+/-6.2 mmHg2 for LF of diastolic and of systolic blood pressure, P<0.05). Values returned to predialysis levels after the end of the dialysis session in all patients. We conclude that standard haemodialysis activates a marked and reversible sympathetic response in both stable and unstable uraemic patients. However, in unstable patients, such activation is impaired in late dialysis, therefore contributing to the onset of the hypotensive crisis.

Signal-averaged ECG abnormalities in haemodialysis patients. Role of dialysis.

BACKGROUND: Late potentials (LP) on the signal-averaged electrocardiogram (SAECG) are predictive of malignant ventricular arrhythmias and sudden cardiac death in patients with ischaemic and non-ischaemic cardiomyopathy. Cardiac dysfunction, both regional and global, as well as supraventricular and ventricular arrhythmias are reported in a high percentage of patients with end-stage renal failure (ESRF). The aim of the study was to assess the prevalence of LP and the effects of haemodialysis on the SAECG of ESRF patients. METHODS: SAECG was recorded immediately before and within 30 min after the end of dialysis in 48 patients in sinus rhythm, free of conduction disturbances on ECG and of signs of congestive heart failure. Serum electrolytes were sampled together with the SAECG recordings. An echo-Doppler exam was performed within 2 weeks of the study. SAECGs were adequate for analysis in 45/48 patients. LP were present when at least two of the following criteria were fulfilled: QRS duration < or = 115 ms, LAS40 < or = 38 ms, RMS40 > or = 38 microV at 40 Hz high pass bidirectional filter, and noise <0.7 microV. RESULTS: LP were detected in 12/45 patients (25%) on the SAECG before dialysis; of these 12 patients, seven had a history of a previous myocardial infarction and two had documented coronary artery disease (CAD). A significant greater wall motion score index--calculated on a 16 segment model--was reported in patients with LP (1.20+/-0.20 vs 1.01+/-0.03, P<0.01), while left ventricular mass was comparable in the two groups of patients. At the end of dialysis, a significant prolongation of fQRS duration was found both at 25 and 40 Hz filters (from 98+/-11 to 106+/-16 ms and from 97+/-12 s to 102+/-13 ms, respectively, P<0.001). A significant inverse relationship was seen between the percentage of dialysis-induced serum potassium reduction and fQRS changes at 40 Hz (r=-0.68, P<0.001). CONCLUSIONS: LP were detected in a significant proportion of dialysis patients, probably related to underlying CAD with left ventricular dysfunction. Prolongation of fQRS after dialysis could be explained by the acute reduction in serum potassium levels.

Early assessment of coronary reserve after bypass surgery by dipyridamole transesophageal echocardiographic stress test.

The evaluation of coronary reserve within a few hours of aortocoronary bypass surgery could be of extreme utility for the follow-up or therapeutical management of these patients. In 11 men patients who underwent aortocoronary bypass surgery, a dipyridamole echocardiography stress test was carried out before (1 to 3 days), early after (68 to 130 minutes), and 1 week after surgery. The first and third tests were performed using a standard transthoracic approach, while the second was performed by a transesophageal approach. Dipyridamole was administered intravenously at a dose of 0.56 mg/kg body weight (low dose) and eventually adding 0.28 mg/kg body weight (high dose), always in the absence of antiischemic therapy. An arbitrary wall motion score (0 = eukinesia; 1 = hypokinesia; 2 = akinesia; 3 = dyskinesia) was assigned to the seven different myocardial regions in which the left ventricle was divided in order to have a semiquantitative score. Under basal conditions wall motion score per patient in the three series of tests did not change significantly (1.6, 1.4, and 1.5, respectively), while the mean score during dipyridamole administration showed significant differences (3.6, 1.9, and 1.9, respectively), indicative of the results obtained by surgical repair. The test, positive in all patients before surgery, showed wall motion abnormalities and ischemic ECG changes in two patients immediately after surgery by the transesophageal approach. One patient who had a normal basal contraction pattern and an abnormal response after the test developed in the following days a perioperative myocardial infarction, while a second patient in the follow-up period developed low-level effort angina.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrafiltration: a rational treatment for heart failure.

Patients with late-stage congestive heart failure with significant fluid overload respond well to ultrafiltration. The response is relatively long-standing and includes enhanced responsiveness to diuretics. Ultrafiltration is simple and highly cost effective. Furthermore, it possesses many advantages over massive or drastic pharmacological therapy. In the following paper, we report our own experience and review the world literature.