Exercise Training in Post-COVID-19 Patients: The Need for a Multifactorial Protocol for a Multifactorial Pathophysiology.

The battle against COVID-19 has entered a new phase with Rehabilitation Centres being among the major players, because the medical outcome of COVID-19 patients does not end with the control of pulmonary inflammation marked by a negative virology test, as many patients continue to suffer from long-COVID-19 syndrome. Exercise training is known to be highly valuable in patients with cardiac or lung disease, and it exerts beneficial effects on the immune system and inflammation. We therefore reviewed past and recent papers about exercise training, considering the multifactorial features characterizing post-COVID-19 patients' clinical conditions. Consequently, we conceived a proposal for a post-COVID-19 patient exercise protocol as a combination of multiple recommended exercise training regimens. Specifically, we built pre-evaluation and exercise training for post-COVID-19 patients taking advantage of the various programs of exercise already validated for diseases that may share pathophysiological and clinical characteristics with long-COVID-19.

Prognostic value of global left atrial peak strain in patients with acute ischemic stroke and no evidence of atrial fibrillation.

Prognostic stratification of acute ischemic stroke (AIS) patients without atrial fibrillation (AF) remains a challenge. Two-dimensional speckle tracking echocardiography (2D-STE) has recently been introduced for dynamic evaluation of left atrial function. However only few data are actually available regarding the application of 2D-STE in AIS patients. The aim of our study was to assess the prognostic role of global left atrial peak strain (GLAPS), measured by 2D-STE, in AIS patients without AF history. Eighty-five AIS patients (mean age 74.1 ± 12.1 years, 49 males) with normal sinus rhythm on ECG and without AF history were enrolled in the prospective study. All patients underwent a complete echocardiographic study with 2D-STE. At 1 year follow-up, we evaluated the occurrence of a composite endpoint of all-cause mortality plus cardiovascular re-hospitalizations. GLAPS was markedly reduced in AIS patients (15.71 ± 4.70%), without any statistically significant difference between the stroke subtypes. At 1-year follow-up, 14 deaths and 17 hospital readmissions were detected in AIS subjects. On a multivariate Cox model, variables independently associated with the occurrence of the composite endpoint were the "Rankin in" Scale (HR 1.69, p = 0.001), GFR (HR 0.98, p = 0.03) and the GLAPS value (HR 0.78, p < 0.0001). A GLAPS value ≤ 15.5% predicted the composite endpoint with sensitivity of 100% and specificity of 80%. A GLAPS value ≤ 15.5% reflects a more advanced atrial cardiomyopathy and might provide a reliable and useful prognostic risk stratification of AIS patients without AF history.

AnatoMy and physIopathoLogy of the heArt in a ceNtenarian cOhort (MILANO study).

Background: Centenarians are increasingly being encountered in clinical practice. The aim of the study was to characterize centenarians' clinical features and cardiovascular system. Methods: A prospective, observational, cross-sectional, case-control study included 118 hospitalized >100-year-old patients compared to 50 octogenarians, selected in Milan (Italy) from December 2010 to December 2017, to assess their clinical and echocardiographic characteristics. Results: Centenarians were mostly women with small body surface area; long history of hypertension; chronic renal failure; and low incidence of smoking, diabetes, dyslipidemia, hyperuricemia, coronary artery disease, atrial fibrillation, and cerebrovascular disease. They showed high prevalence of severe cognitive impairment and disability. Almost half of patients (46%) were hospitalized for congestive heart failure (HF), mostly diastolic (80% of cases). Centenarians' hearts had reduced left ventricular end-diastolic dimensions (25.3 ± 3.8 mm/m^2), increased septal thickness (13.3 ± 1.9 mm), and higher relative wall thickness (0.58 ± 0.1). The ejection fraction was usually normal and rarely depressed (57.1% ± 11.7%), whereas the E/e' ratio was considerably increased (17.0 ± 6.0). Noninvasive evaluation of ventricular-arterial coupling parameters revealed significantly higher values of LV end-diastolic elastance in all centenarians versus octogenarians (0.4 ± 01 mm Hg/mL/m^2 vs 0.18 ± 0.2 mm Hg/mL/m^2, P < .0001) and in centenarians with HF versus those without HF (0.5 ± 0.1 mm Hg/mL/m^2 vs 0.34 ± 0.1 mm Hg/mL/m^2, P < .0001). Conclusions: The centenarians' cardiovascular system manifested a significant increase in LV diastolic stiffness with consequent susceptibility to diastolic HF. A progressive afterload increase and a passive load independent mechanism could have contributed to such changes.

A New modified anthropometric haller index obtained without radiological exposure.

To validate a new modified method for measuring the anthropometric Haller index (HI), obtained without radiological exposure. This new method was based on the use of a rigid ruler and of a 2.5 MHz ultrasound transducer for the assessment of latero-lateral and antero-posterior chest diameters, respectively. We enrolled 100 consecutive patients (mean age 67.9 ± 14.5 years, 55% males), who underwent a two-plane CXR, for any clinical indication, over a four-month period. In all patients, the same radiologist calculated the conventional radiological HI (mean value 1.93 ± 0.35) and the same cardiologist used the above described new technique to measure the modified HI (mean value 1.99 ± 0.26). The Bland-Altman analysis showed tight limits of agreement (+ 0.37; - 0.51) between the two measurement methods, with a mild systematic overestimation of the new method as compared to the standard radiological HI. The Pearson's correlation analysis highlighted a strong correlation between the two methods (r = 0.81, p < 0.0001), while the Student's t test demonstrated a not statistically difference between the means (p = 0.12). The modified HI might allow a quick description of the chest conformation without radiological exposure and a more immediate comprehension of its possible influence on the cardiac kinetics and function, as assessed by echocardiography or other imaging modalities.

Hemodynamic Mechanisms of Exercise-Induced Pulmonary Hypertension in Patients with Lymphangioleiomyomatosis: The Role of Exercise Stress Echocardiography.

BACKGROUND: The pathogenesis of pulmonary hypertension (PH) in lymphangioleiomyomatosis (LAM) has not yet been completely clarified. The aim of this study was to conduct a noninvasive evaluation of the main hemodynamic mechanisms of exercise-induced PH in patients with LAM, assessed using exercise stress echocardiography. METHODS: Fifteen patients with LAM (mean age, 47 ± 13 years; all women) without resting PH were enrolled in a prospective single-center study and compared with 15 healthy female control subjects (mean age, 45.2 ± 8 years; P = .65). A complete echocardiographic study with Doppler tissue imaging was performed at baseline and during semisupine symptom-limited exercise testing to evaluate (1) left ventricular systolic and diastolic function, (2) right ventricular contractile function, (3) estimated pulmonary capillary wedge pressure, (4) estimated systolic and mean pulmonary artery pressure, and (5) estimated pulmonary vascular resistance. RESULTS: Compared with healthy control subjects, patients with LAM during exercise showed echocardiographic signs of right ventricular overload and right ventricular systolic dysfunction and significant increases in mean pulmonary artery pressure (14.4 ± 6.5 vs 4.2 ± 3.1 mm Hg, P < .0001), pulmonary vascular resistance (+68.3 ± 42.1 vs -0.1 ± 18.3 dyne-sec/cm5, P < .0001), and, unexpectedly, pulmonary capillary wedge pressure (+8.3 ± 5.3 vs -0.5 ± 1.3 mm Hg, P < .0001). CONCLUSIONS: Exercise-induced PH in patients with LAM could be related not only to hypoxic pulmonary vascular vasoconstriction during exercise (precapillary PH) but also to a significant exercise-induced increase in estimated pulmonary capillary wedge pressure, probably secondary to diastolic dysfunction (postcapillary PH).

Ventricular-arterial coupling in centenarians without cardiovascular diseases.

BACKGROUND: Ventricular-arterial (VA) coupling is a central determinant of cardiovascular system performance and cardiac energetics. This index is expressed by the Ea/Ees ratio, where the effective arterial elastance (Ea) indicates the net arterial load exerted on the left ventricle and the left ventricular end-systolic elastance (Ees) is a load-independent measure of left ventricular chamber performance. METHODS: Thirty-three centenarians (100.6 ± 1.2 years, range 99-105 years, 10 M) without cardiovascular diseases underwent a complete echocardiographic evaluation and an instantaneous arterial blood pressure measurement, to characterize the Ea/Ees ratio and its two determinants indexed to body surface area. RESULTS: VA coupling was markedly reduced (Ea/Ees ratio 0.40 ± 0.1), reflecting a disproportionate increase in Ees index (8.5 ± 2.2 mmHg/ml/m2) compared with Ea index (3.2 ± 0.8 mmHg/ml/m2). Notably, the coupling ratio was significantly lower in women (0.37 ± 0.1) than in men (0.45 ± 0.1, p = 0.0003), due to an increase in Ees index significantly greater in women (9.4 ± 1.9 mmHg/ml/m2) than in men (6.5 ± 1.5 mmHg/ml/m2, p = 0.0002). Using multivariate regression analysis, only female gender (ß coefficient -0.04, p = 0.01) and relative wall thickness (ß coefficient -0.49, p < 0.0001) showed a significant inverse correlation to VA coupling. CONCLUSIONS: Our analysis in a population of centenarians without overt cardiovascular disease revealed very low values of VA coupling, especially in women. Both a LV structural remodeling as well as a high aortic elastance might have contributed to a secondary disproportionate increase in myocardial stiffness.

Exercise stress echocardiography with tissue Doppler imaging in risk stratification of mild to moderate aortic stenosis.

BACKGROUND: Patients with mild to moderate aortic stenosis (AS) seem to have a worse outcome than commonly expected. Early identification of subjects who may develop a rapid disease progression or cardiovascular events is critical in order to apply adequate risk management. STUDY DESIGN: Observational prospective single-centre study. OBJECTIVE: To determine the prognostic role of exercise stress echocardiography (ESE) in patients with mild and moderate asymptomatic AS. PATIENTS: Ninety consecutive patients (mean age 74 ± 12 years) with isolated mild and moderate AS were enrolled into the study protocol over a 20 months period. Follow-up time was 12 months. METHODS: A complete echocardiographic study with tissue Doppler imaging (TDI) was performed at baseline and during semi-supine symptom-limited exercise test to evaluate: (1) the occurrence of symptoms, (2) ST segment changes, (3) transaortic pressure gradient, (4) the E/A ratio, (5) the E/e' ratio and (6) the systolic pulmonary artery pressure. MAIN OUTCOME MEASURES: During the 1 year follow-up time, we evaluated the occurrence of adverse cardiac events, defined as any of the following: (1) cardio-vascular hospitalization; (2) requirement for aortic valve replacement; (3) cardiac death. RESULTS: During follow-up, three patients died, 11 underwent aortic valve replacement and 26 had cardiovascular hospitalizations. On univariate analysis, patients who exhibited symptoms during exercise (HR 2.93, p = 0.003); the occurrence of a ≥ 2 mm exercise-induced ST segment depression (HR 3.12, p = 0.001); a ≥ 15 mmHg increase in mean transaortic pressure gradient during exercise (HR 2.77, p = 0.001); a ≥ 50 mmHg exercise-induced increase in systolic pulmonary artery pressure (HR 2.90, p = 0.009); an exercise-induced pseudo-normalization of the E/A ratio (E/A ≥ 1) (HR 7.50, p = 0.0001) and, particularly, a ≥ 15 exercise-induced increase in the E/e' ratio (HR 7.69, p = 0.0001) had a significantly higher risk of cardiac events during the follow-up time. On multivariate analysis, only the latter covariate (HR 6.04, p = 0.009) was independently associated with adverse cardiac events. CONCLUSIONS: A ≥ 15 stress-induced increase in E/e' ratio is highly predictive of cardiac events in patients with mild to moderate AS. Assessment of diastolic function using TDI during ESE provides additional prognostic information in such patients.

[Giant left atrium in a patient with decompensated heart failure]. / Atrio sinistro gigante in una paziente con scompenso cardiaco riacutizzato.

A 71-year-old woman was admitted to our institution with symptoms and signs of acute congestive heart failure. The patient had a long history of rheumatic heart disease and, in 1974, she had undergone mitral valve replacement with a single tilting-disk mechanical valve. Transthoracic echocardiography showed a giant left atrium, measuring 18.5 cm longitudinally and 17 cm transversely from the apical four-chamber view with a volume of 1706 ml/m2 body surface area, associated with intense spontaneous echocontrast. Massive tricuspid regurgitation and severe pulmonary hypertension were diagnosed. It could be hypothesized that the giant left atrium may have contributed to the development of acute decompensated heart failure resulting in a significant reduction of left ventricular preload.

[Major epidemiological changes and clinical variables in patients undergoing a program of heart rehabilitation after cardiac surgery - MEPHISTOPHELES]. / Major epidemiological changes and clinical variables in patients undergoing a program of heart rehabilitation after cardiac surgery - MEPHISTOPHELES.

BACKGROUND: Recent observational studies show an increase of more complex and critically ill patients referred to Italian cardiac rehabilitation (CR) departments; the exact mechanisms underlying this phenomenon, however, have not been clearly identified. The aim of our study was to evaluate the epidemiological and clinical changes that occurred over the last decade in patients hospitalized in CR departments with high admittance rates. METHODS: We have retrospectively evaluated all patients admitted between 2002 and 2009 to our division of CR (n = 3340, 1155 female, mean age 66.4 ± 11 years) after recent cardiac surgery. The study population was divided into two homogeneous groups: the four-year period 2002-2005, group A (n = 1614, 540 female, mean age 66.1 ± 10 years) and the four-year period 2006-2009, group B (n = 1726, 615 female, mean age 67.4 ± 11 years). Data were compared using specific indicators of clinical complexity. RESULTS: Patients aged >75 years were more in group B compared to A (26.3 vs 19.8%, p<0.0001), as well as patients with recent complex surgical interventions, such as combined coronary artery bypass grafting and heart valve surgery (16.4 vs 10.2%, p<0.0001). An increased incidence of cardiovascular death (1.4 vs 0.6%, p=0.02), acute coronary syndrome (1.5 vs 0.7%, p=0.02) and persistent atrial fibrillation/flutter (13.5 vs 7.1%, p<0.0001) was observed in group B, as well as an increased prevalence of systolic heart failure (18.3 vs 9.0%, p<0.0001). Similarly, the incidence of acute respiratory failure episodes (1.0 vs 0.4%, p=0.05), the prevalence of patients admitted with a tracheostomy tube (2.6 vs 0.2%, p<0.0001) and the incidence of acute renal failure (1.1 vs 0.5%, p=0.05) were significantly increased in group B. Postoperative infections and surgical wound complications were 4-fold higher in group B (13.9 vs 3.1%, p<0.0001, and 12.8 vs 2.3%, p<0.0001, respectively). Compared to group A, patients of group B showed a significantly lower physical performance, as expressed by the Rivermead motility index (3.8 ± 1.1 vs 5.2 ± 0.8, p<0.001); moreover, the number of subjects able to perform an incremental training program was significantly lower in group B than group A (14.8 vs 60.6%, p<0.0001). Mean hospital stay was longer in group B than group A (25.4 ± 13 vs 22.1 ± 9 days, p<0.001). CONCLUSIONS: Our study, by collecting data from a CR division in northern Italy with high admittance rates, demonstrates a dramatic increase in clinical complexity over the last few years. This points to the need for new expertise and major resources to be allocated to CR departments.

Cardio-oncology in targeting the HER receptor family: the puzzle of different cardiotoxicities of HER2 inhibitors.

The HER family of tyrosine kinase receptors includes several members that are clinically important targets in cancer therapies, in particular HER1 (the EGF receptor) and HER2, other members include HER3 and HER4. Trastuzumab, a humanized monoclonal antibody and lapatinib, a tyrosine kinase inhibitor, are drugs that target HER2, which is highly expressed in 20-30% of breast cancers. Trastuzumab is recommended as an adjuvant therapy for lymph node positive, HER2-positive breast cancers, or node-negative cancer with high-risk of recurrence, as well as in stage IV cancers. One serious side effect of trastuzumab is cardiomyocyte dysfunction, resulting in reduced heart contractile efficiency. The incidence of collateral effects on the heart with trastuzumab therapy increases in people with cardiovascular risk factors, heart disease and when combined with other chemotherapeutics. When cardiotoxicity was observed with trastuzumab, several studies have addressed potential cardiac damage of trastuzumab itself and lapatinib. The differences in cardiovascular effects of these two compounds are somewhat unexpected and suggest distinct mechanisms of action, which have clear implications in clinical application and prevention of cardiotoxicity in cardio-oncological approaches.

Low-risk profile for malignant ventricular arrhythmias and sudden cardiac death after surgical ventricular reconstruction.

BACKGROUND: Although it has been recently demonstrated that there was no significant difference in total survival and clinical outcomes between patients who underwent coronary artery bypass grafting (CABG) with or without surgical ventricular reconstruction (SVR), the question of whether or not SVR decreases the arrhythmic risk profile in this population has not been clarified yet. OBJECTIVE: To determine the real incidence of sudden cardiac death (SCD) and sustained ventricular tachycardia/ventricular fibrillation (sustained VT/VF) in patients following CABG added to SVR and to define their clinical and echocardiographic parameters predicting in-hospital and long-term arrhythmic events (SCD + sustained VT/VF). METHODS: Pre- and postoperative clinical and echocardiographic values as well as postoperative electrocardiogram Holter data of 65 patients (21 female, 63 ± 11 years) who underwent SVR + CABG were retrospectively evaluated. RESULTS: Mean follow-up was 1,105 ± 940 days. At 3 years, the SCD-free rate was 98% and the rate free from arrhythmic events was 88%. Multivariate logistic analysis identified a preoperative left ventricular end-systolic volume index (LVESVI) > 102 mL/m(2) (odds ratio [OR] 1.4, confidence interval [CI] 1.073-1.864, P = 0.02; sensitivity 100%, specificity 94%) and a postoperative pulmonary artery systolic pressure (PASP) > 27 mmHg (OR 2.3, CI 1.887-4.487, P = 0.01; sensitivity 100%, specificity 71%) as independent predictors of arrhythmic events. CONCLUSIONS: Our and previous studies report a low incidence of arrhythmic events in patients following SVR added to CABG, considering the high-risk profile of the study population. A preoperative LVESVI > 102 mL/m(2) and a postoperative PASP > 27 mmHg had a good sensitivity and specificity in predicting arrhythmic events.

Tako-tsubo cardiomyopathy complicated by ventricular septal perforation and septal dissection.

Tako-tsubo cardiomyopathy is a form of reversible left ventricular dysfunction, with a clinical and electrocardiographic picture of acute myocardial infarction in the absence of significant coronary disease. The precise clinical features and etiologic basis of this syndrome remain unclear, although an association with emotional or stressful triggers has been recognized. We describe the first case of this syndrome complicated with a ventricular septal perforation and dissection.

[Diagnosis and management of dysphagia in patients with tracheostomy tube after cardiac surgery: an early screening protocol]. / Come riconoscere e gestire la disfagia nel cardioperato tracheostomizzato: proposta di un protocollo di screening.

SCOPE: Patients with tracheostomy tube after major cardiac surgery undergoing Cardiac Rehabilitation Program often present swallowing disorders that need a specific evaluation. This study aimed at validating the usefulness of a swallowing screen protocol in order to obtain an early assessment of dysphagia and to prevent aspiration, malnutrition and dehydration risks. MATERIALS AND METHODS: The protocol has been applied to 38 consecutive patients with tracheostomy tube after cardiac surgery between September 2007 and December 2009. The average age of patients was 73 +/- 6 years; the average value of left ventricular ejection fraction was 41 +/- 4%. The protocol included a water swallowing test and a specific swallowing test with blue dye. During tests, the presence of signs of swallowing dysfunction was evaluated and oxygen saturation levels were monitored. RESULTS: Out of 38 patients, 2 did not show any swallowing deficits; 18 showed deficits in the water swallowing test even though they presented a preserved swallowing function during specific swallowing test. All these 20 patients (53%), before discharge, restarted an oral feeding and obtained an adequate body mass index and effective coughing, so they were soon decannulated. Twelve patients (31%) showed deficits during the water swallowing test, confirmed by the specific swallowing test with blue dye: the tracheostomy tube was not removed and a specific program of swallowing rehabilitation was performed. Before discharge all patients restarted an oral feeding, recovered an effective coughing and were decannulated. Six patients (16%), because of persistent dysphagia, underwent percutaneous endoscopic gastrostomy. None of these 38 patients developed ab ingestis pneumonia, dehydration or malnutrition. CONCLUSIONS: An early assessment of swallowing in patients with tracheostomy tube after cardiac surgery allows the selection of patients with higher aspiration risk, preventing possible severe complications.

Ejection fraction/velocity ratio identifies prosthesis-patient mismatches in patients with aortic bioprosthetic valves and left ventricular dysfunction.

OBJECTIVES: Recently, a new echocardiographic nonflow corrected index (ejection fraction/velocity ratio [EFVR] = percent left ventricular ejection fraction [EF]/maximum aortic gradient) has been introduced and has shown excellent accuracy in quantifying the effective orifice area (EOA) in native aortic valves and bio-prostheses. The objective of this study was to assess the utility of the EFVR to quantify the indexed EOA in patients with an aortic bioprosthesis and left ventricular dysfunction considering an indexed EOA value of 0.85 cm(2)/m(2) or less to be indicative of a prosthesis-patient mismatch (PPM), defined as an EOA of the inserted prosthetic valve of less than that of the normal human valve. METHODS: We studied 100 patients (62 men and 38 women; mean age +/- SD, 71 +/- 8.6 years) with an aortic bioprosthesis and left ventricular dysfunction (EF < or =49%), and we evaluated the indexed EOA by both the continuity equation (CE) and EFVR. RESULTS: We found a significant linear correlation between the CE and EFVR (r = 0.85; P < .0001) and good agreement between the two methods in identifying patients with an indexed EOA of 0.85 cm(2)/m(2) or less; the correlation began to become nonlinear for patients with an indexed EOA of greater than 1.2 cm(2)/m(2), which was not clinically relevant. Notably, all 11 patients with a discrepancy between the indexed EOA and EFVR (ie, EFVR < or =1.0 and indexed EOA >0.85 cm(2)/m(2)) also showed an indexed EOA of greater than 0.85 but less than or equal to 1.0 cm(2)/m(2) (meaning the presence of a mild PPM). CONCLUSIONS: The EFVR can be considered a reliable echocardiographic alternative to the CE, especially in conditions in which that is technically difficult, allowing identification of a PPM (indexed EOA < or =0.85 cm(2)/m(2)) with excellent sensitivity and specificity.

The embolic storm: dramatic peripheral complications of left ventricular thrombosis after myocardial infarction.

Left ventricular thrombus is a common complication after acute myocardial infarction. Although anticoagulant treatment has an established role in reducing the rate of thrombus formation and embolic phenomena during acute myocardial infarction, prior studies showed that left ventricular thrombus and systemic embolization may develop irrespective of adequate anticoagulant therapy. We present a descriptive case of a patient with left ventricular thrombus who experienced dramatic peripheral embolic events soon after the onset of anterior myocardial infarction despite full anticoagulation, and we discuss possible pathogenesis.