Cardiac rehabilitation and acute aortic dissection: understanding and addressing the evidence GAP a systematic review.

Despite guideline recommendations, strategies for implementing cardiac rehabilitation (CR) in patients with acute aortic dissection (AAD) are not well established with little evidence to risk stratify prudent and effective guidelines for the many required variables. We conducted a systematic review of studies (2004-2023) reporting CR following type A (TA) and type B (TB) AAD. Our review is limited to open surgical repair for TA and medical treatment for TB. A total of 5 studies were included (4 TA-AAD and 1 TB-AAD) in the qualitative analysis. In general, observational data included 311 patients who had an overall favorable effect of CR in AAD consisting of a modestly improved exercise capacity and work load during cycle cardiopulmonary exercise test (TB-AAD), and improved quality of life (QoL). No adverse events were reported during symptom limited pre-CR treadmill or cycle exercise VO2 max or CR. Given the overall potential in this high risk population without adequate evidence for important variables such as safe time from post-op to CR, intensity of training, duration and frequency of sessions and followup it is time for a moderate sized well designed safe trial for patients' post-op surgery for TA-AAD and medically treated TB-AAD who are treated with standardized evidence based medical therapy and physical therapy from discharge randomized to CR versus usual care. PROSPERO registry ID: CRD42023392896.

Health-related quality of life in patients with aortic dissection: An unmet need.

Knowledge about the Health-related Quality of Life (HR-QoL) after Type A (TA-AAD) and Type B acute aortic dissection (TB-AAD) is still insufficient. Through this systematic review, including 22 studies (16 for TA-AAD and 6 TB-AAD -1998-2023), the entire literature on HR-QoL after surgical and/or endovascular and/or medical interventions has been investigated. In TA-AAD patients, despite overall SF-36 score was similar to the standard population, with > 80 years patients displaying a better emotional domain, the SF-12 was significant lower to controls in physical and mental well-being domains. Exercise-based cardiac rehabilitation improved HR-QoL. In TB-AAD, vitality and mental health SF-36 scores improved after thoracic endovascular aortic repair (TEVAR); long-term QoL was similar in the open surgery group compared to TEVAR. Overall, HR-QoL after AAD seems adequate irrespective of age or sex, except for some specific domains. Physical exercise and cardiac rehabilitation may improve HR-QoL in these patients. PROSPERO registry ID: CRD42023421130.

Exercise Stress Echocardiography of the Right Ventricle and Pulmonary Circulation.

BACKGROUND: Exercise echocardiography is used for assessment of pulmonary circulation and right ventricular function, but limits of normal and disease-specific changes remain insufficiently established. OBJECTIVES: The objective of this study was to explore the physiological vs pathologic response of the right ventricle and pulmonary circulation to exercise. METHODS: A total of 2,228 subjects were enrolled: 375 healthy controls, 40 athletes, 516 patients with cardiovascular risk factors, 17 with pulmonary arterial hypertension, 872 with connective tissue diseases without overt pulmonary hypertension, 113 with left-sided heart disease, 30 with lung disease, and 265 with chronic exposure to high altitude. All subjects underwent resting and exercise echocardiography on a semirecumbent cycle ergometer. All-cause mortality was recorded at follow-up. RESULTS: The 5th and 95th percentile of the mean pulmonary artery pressure-cardiac output relationships were 0.2 to 3.5 mm Hg.min/L in healthy subjects without cardiovascular risk factors, and were increased in all patient categories and in high altitude residents. The 5th and 95th percentile of the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio at rest were 0.7 to 2.0 mm/mm Hg at rest and 0.5 to 1.5 mm/mm Hg at peak exercise, and were decreased at rest and exercise in all disease categories and in high-altitude residents. An increased all-cause mortality was predicted by a resting tricuspid annular plane systolic excursion to systolic pulmonary artery pressure <0.7 mm/mm Hg and mean pulmonary artery pressure-cardiac output >5 mm Hg.min/L. CONCLUSIONS: Exercise echocardiography of the pulmonary circulation and the right ventricle discloses prognostically relevant differences between healthy subjects, athletes, high-altitude residents, and patients with various cardio-respiratory conditions. (Right Heart International NETwork During Exercise in Different Clinical Conditions; NCT03041337).

Mapping acute neuroinflammation in vivo with diffusion-MRI in rats given a systemic lipopolysaccharide challenge.

It is becoming increasingly apparent that neuroinflammation plays a critical role in an array of neurological and psychiatric disorders. Recent studies have demonstrated the potential of diffusion MRI (dMRI) to characterize changes in microglial density and morphology associated with neuroinflammation, but these were conducted mostly ex vivo and/or in extreme, non-physiological animal models. Here, we build upon these studies by investigating the utility of well-established dMRI methods to detect neuroinflammation in vivo in a more clinically relevant animal model of sickness behavior. We show that diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) indicate widespread increases in diffusivity in the brains of rats given a systemic lipopolysaccharide challenge (n = 20) vs. vehicle-treated controls (n = 12). These diffusivity changes correlated with histologically measured changes in microglial morphology, confirming the sensitivity of dMRI to neuroinflammatory processes. This study marks a further step towards establishing a noninvasive indicator of neuroinflammation, which would greatly facilitate early diagnosis and treatment monitoring in various neurological and psychiatric diseases.

Multimodality imaging of a cardiac paraganglioma: A case report.

Cardiac paragangliomas (PGLs) are rare extra-adrenal tumors that arise from chromaffin cells of the sympathetic ganglia. PGLs are often diagnosed incidentally, in the absence of symptoms, or with symptoms related to cardiovascular dysfunction. Cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) can be used to accurately determine the lesion morphology and position as well as providing detailed tissue characterization. A multimodal imaging approach, not yet standardized, could be useful either in diagnosis and monitoring or in treatment planning. In the case reported here, CCT and CMR were performed to define lesion anatomy, and a reconstruction was generated using cinematic rendering (CR) to characterize the PGL angioarchitecture.

4D-Flow Cardiovascular Magnetic Resonance Sequence for Aortic Assessment: Multi-Vendor and Multi-Magnetic Field Reproducibility in Healthy Volunteers.

OBJECTIVES: Four-dimensional (4D) flow cardiac magnetic resonance (CMR) represents an emerging technique for non-invasive evaluation of the aortic flow. The aim of this study was to investigate a 4D-flow CMR sequence for the assessment of thoracic aorta comparing different vendors and different magnetic fields of MR scanner in fifteen healthy volunteers. METHODS: CMR was performed on three different MRI scanners: one at 1.5 T and two at 3 T. Flow parameters and planar wall shear stress (WSS) were extracted from six transversal planes along the full thoracic aorta by three operators. Inter-vendor comparability as well as scan-rescan, intra- and interobserver reproducibility were examined. RESULTS: A high heterogeneity was found in the comparisons for each operator and for each scanner in the six transversal planes analysis (Friedman rank-sum test; p-value ≤ 0.05). Among all, the most reproducible measures were extracted for the sinotubular junction plane and for the flow parameters. CONCLUSIONS: Our results suggest that standardized procedures have to be defined to make more comparable and reproducible 4D-flow parameters and mainly, clinical impactfulness. Further studies on sequences development are needed to validate 4D-flow MRI assessment across vendors and magnetic fields also compared to a missing gold standard.

Cardiovascular Side Effects of Anthracyclines and HER2 Inhibitors among Patients with Breast Cancer: A Multidisciplinary Stepwise Approach for Prevention, Early Detection, and Treatment.

Cardiovascular (CV) diseases (CVD) are a major cause of long-term morbidity and mortality affecting life expectancy amongst cancer survivors. In recent years, because of the possibility of early diagnosis and the increased efficacy of neo-adjuvant and adjuvant systemic treatments (targeting specific molecular pathways), the high percentage of survival from breast cancer led CVD to become the first cause of death among survivors. Therefore, it is mandatory to adopt cardioprotective strategies to minimize CV side effects and CVD in general in breast cancer patients. Cancer therapeutics-related cardiac dysfunction (CTRCD) is a common group of side effects of chemotherapeutics widely employed in breast cancer (e.g., anthracycline and human epidermal growth factor receptor 2 inhibitors). The aim of the present manuscript is to propose a pragmatic multidisciplinary stepwise approach for prevention, early detection, and treatment of cardiotoxicity in patients with breast cancer.

Acute Heart Failure: Diagnostic-Therapeutic Pathways and Preventive Strategies-A Real-World Clinician's Guide.

Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical heterogeneity of the syndrome. Regardless of the underlying mechanism, peripheral and/or pulmonary congestion is present in the vast majority of cases. Furthermore, a marked reduction in cardiac output with peripheral hypoperfusion may occur in most severe cases. Diagnosis is made on the basis of signs and symptoms, laboratory, and non-invasive tests. After exclusion of reversible causes, AHF therapeutic interventions mainly consist of intravenous (IV) diuretics and/or vasodilators, tailored according to the initial hemodynamic status with the addition of inotropes/vasopressors and mechanical circulatory support if needed. The aim of this review is to discuss current concepts on the diagnosis and management of AHF in order to guide daily clinical practice and to underline the unmet needs. Preventive strategies are also discussed.

Exploring the Cardiotoxicity Spectrum of Anti-Cancer Treatments: Definition, Classification, and Diagnostic Pathways.

Early detection and treatment of cancer have led to a noticeable reduction in both mortality and morbidity. However, chemotherapy and radiotherapy could exert cardiovascular (CV) side effects, impacting survival and quality of life, independent of the oncologic prognosis. In this regard, a high clinical index of suspicion is required by the multidisciplinary care team in order to trigger specific laboratory tests (namely natriuretic peptides and high-sensitivity cardiac troponin) and appropriate imaging techniques (transthoracic echocardiography along with cardiac magnetic resonance, cardiac computed tomography, and nuclear testing (if clinically indicated)), leading to timely diagnosis. In the near future, we do expect a more tailored approach to patient care within the respective community along with the widespread implementation of digital health tools.

Sex differences in type A acute aortic dissection: a systematic review and meta-analysis.

BACKGROUND: In acute aortic dissection (AAD) sex heterogeneity reports are not exhaustive and in part even conflicting. AIMS: To explore sex differences in clinical features, management, and outcomes among patients with type A AAD. METHODS AND RESULTS: A systematic review and meta-analysis of the literature were conducted for studies (2004-2022) reporting type A AAD sex differences. Among the 1938 studies retrieved, 16 (16 069 patients, 7142 women, and 8927 men) fulfilled all eligibility criteria. Data were aggregated used the random-effects model as pooled risk ratio and mean difference. Due to information reported by considered manuscripts, analysis were performed only among surgically treated type A AAD patients. At the time of hospital presentation type A AAD women were older than men but had lower body mass index (BMI), body surface area (BSA), and creatinine plasma levels. Active smoking, bicuspid aortic valve, and previous cardiac surgery were less common in women while diabetes mellitus was more frequent. Furthermore, women experienced more frequently pericardial effusion/cardiac tamponade than men. Interestingly, in-hospital surgical mortality did not differ between sexes [risk ratio (RR), 1.02; 95% confidence interval (CI), 0.53-1.99; P = 0.95], whereas 5 (RR 0.94; 95% CI: 0.92-0.97; P < 0.001) and 10-year survival (RR 0.82; 95% CI: 0.74-0.92; P = 0.004) was higher among men. A descriptive analysis of in-hospital outcomes among medically treated type A AAD patients confirmed prohibitive high mortality for both sexes (men 58.6% vs. women 53.8%, P = 0.59). CONCLUSIONS: A female sex phenotype appears to be evident in type A AAD implying the need for a personalized management patient approach along with tailored preventive strategies. PROSPERO REGISTRY ID: CRD42022359072.

Reports regarding sex heterogenicity in acute aortic dissection (AAD) are not exhaustive and in part even conflicting. Sex differences in clinical features, management, and outcomes were investigated among patients with type A AAD through a systematic review and meta-analysis of literature. A female sex phenotype appears to be evident in type A AAD implying the need for a personalized management patient approach along with tailored preventive strategies. Interestingly, while in-hospital surgical mortality did not differ between sexes, 5- and 10-year survival was higher among men. In the near future, definitive sex-specific data from international clinical registries and trials are expected.

How to Treat Right Heart Failure. Tips for Clinicians in Everyday Practice.

In recent years, several observations reported that intolerance of physical exertion and other cardinal symptoms in heart failure (HF) are closely related to the functionality of the right ventricular (RV), regardless of left heart. It has been demonstrated that the RV dysfunction complicates the course, aggravates the quality of life, and increases the mortality of HF patients. The present review is aimed to report tips physicians about the current therapeutic management of right HF during acute stage and chronic phase, shedding light on the RV and its failure and providing physicians with essential information for everyday clinical practice.

Severe Stenosis of Mitral Bioprosthetic Valve Thrombosis in a Patient with HCV-Related Cirrhosis and Duodenal Variceal Bleeding: The Deadly Triad.

Bioprosthetic valve thrombosis (BPVT) is considered a relatively rare but life-threatening clinical entity. Thus, there is the need of high clinical suspicion in order to make a timely diagnosis and related appropriate therapeutic interventions. In this regard, the management of BPVT is high risk, whatever the option taken (surgery and/or systemic fibrinolysis). The presence of severe comorbidities-as decompensated cirrhosis-further complicates the clinical decision-making process, calling for a patient-tailored integrated multidisciplinary approach. We report a challenging case of a 45-year-old patient with mitral bioprosthetic valve thrombosis and hepatitis C virus (HCV)-related cirrhosis complicated by active duodenal variceal bleeding.

Effects of Exercise on Heart Failure with Preserved Ejection Fraction: An Updated Review of Literature.

Heart failure with preserved ejection fraction (HFpEF) represents the most common HF phenotype of patients aged > 65 years, with an incidence and a prevalence that are constantly growing. The HFpEF cardinal symptom is exercise intolerance (EI), defined as the impaired ability to perform physical activity and to reach the predicted age-related level of exercise duration in the absence of symptoms­such as fatigue or dyspnea­and is associated with a poor quality of life, a higher number of hospitalizations, and poor outcomes. The evidence of the protective effect between exercise and adverse cardiovascular outcomes is numerous and long-established. Regular exercise is known to reduce cardiovascular events and overall mortality both in apparently healthy individuals and in patients with established cardiovascular disease, representing a cornerstone in the prevention and treatment of many cardio-metabolic conditions. Several studies have investigated the role of exercise in HFpEF patients. The present review aims to dwell upon the effects of exercise on HFpEF. For this purpose, the relevant data from a literature search (PubMed, EMBASE, and Medline) were reviewed. The analysis of these studies underlines the fact that exercise training programs improve the cardiorespiratory performance of HFpEF patients in terms of the increase in peak oxygen uptake, the 6 min walk test distance, and the ventilatory threshold; on the other hand, diastolic or systolic functions are generally unchanged or only partially modified by exercise, suggesting that multiple mechanisms contribute to the improvement of exercise tolerance in HFpEF patients. In conclusion, considering that exercise training programs are able to improve the cardiorespiratory performance of HFpEF patients, the prescription of exercise training programs should be encouraged in stable HFpEF patients, and further research is needed to better elucidate the pathophysiological mechanisms underpinning the beneficial effects described.

Physiologic Range of Myocardial Mechano-Energetic Efficiency among Healthy Subjects: Impact of Gender and Age.

BACKGROUND: Myocardial mechano-energetic efficiency (MEE) is the capability of the left ventricle (LV) to convert the chemical energy obtained from the cardiac oxidative metabolism into mechanical work. The aim of present study was to establish normal non-invasive MEE and MEEi reference values. METHODS: In total, 1168 healthy subjects underwent physical examinations, clinical assessment, and standardized transthoracic echocardiographic (TTE) examination. MEE was obtained by TTE as the ratio between stroke volume (SV) and heart rate (HR): MEE = SV/HR [HR expressed in seconds (HR/60)]. Because MEE is highly related to left ventricular mass (LVM), MEE was then divided by LVM with the purpose of obtaining an estimate of energetic expenditure per unit of myocardial mass (i.e., indexed MEE, MEEi, mL/s/g). RESULTS: The mean values of MEE and MEEi in the overall population were 61.09 ± 18.19 mL/s; 0.45 ± 0.14, respectively. In a multivariable analysis, gender, body surface area (BSA), diastolic blood pressure, left atrial volume indexed to BSA, E/e' and tricuspid annular plane systolic excursion (TAPSE) were the independent variables associated with MEE, while age, gender, BSA and TAPSE were the independent variables associated with MEEi. CONCLUSIONS: The knowledge of age- and gender-based MEE and MEEi normal values may improve the global assessment of LV cardiac mechanics and serve as a reference to identify phenotypes at high risk of cardiovascular events.

Idiopathic pulmonary fibrosis telemedicine management during COVID-19 outbreak.

The present report investigates the impact of a Telemedicine Service (TMS) on the management of Idiopathic Pulmonary Fibrosis (IPF) during coronavirus disease of 2019 (COVID-19) outbreak in Italy. The TMS comprised 3 phone numbers, active 12 h per day, and an email address, monitored every 4 h by trained physicians; chat- and videoconference-services were also offered. At the end of the study period, our staff contacted all patients, to get information about the final outcome (i.e. composite hospitalisations/all causes of death). Outcomes were compared with a cohort of patients who attended our unit in the same period of the previous year (when no TMS was available). 189 patients participated in the present study. From 11th March to 4th May 2020, 61% of patients made at least one TMS access, mostly by emails (53%), followed by phone calls (33%). With regard to the primary outcome, TMS patients experienced a significant lower rate of events of the 182 patients of the no-TMS cohort (p < 0.001). Specifically, a significant difference was observed for IPF hospitalisation (p < 0.001) whereas no differences were observed with regard to deaths (p = 0.64). TMS permits patients to be followed up even during COVID-19 lockdown, with an encouraging impact on outcomes.

Right Heart Pulmonary Circulation Unit Response to Exercise in Patients with Controlled Systemic Arterial Hypertension: Insights from the RIGHT Heart International NETwork (RIGHT-NET).

BACKGROUND: Systemic arterial hypertension (HTN) is the main risk factor for the development of heart failure with preserved ejection fraction (HFpEF). The aim of the study was was to assess the trends in PASP, E/E' and TAPSE during exercise Doppler echocardiography (EDE) in hypertensive (HTN) patients vs. healthy subjects stratified by age. METHODS: EDE was performed in 155 hypertensive patients and in 145 healthy subjects (mean age 62 ± 12.0 vs. 54 ± 14.9 years respectively, p < 0.0001). EDE was undertaken on a semi-recumbent cycle ergometer with load increasing by 25 watts every 2 min. Left ventricular (LV) and right ventricular (RV) dimensions, function and hemodynamics were evaluated. RESULTS: Echo-Doppler parameters of LV and RV function were lower, both at rest and at peak exercise in hypertensives, while pulmonary hemodynamics were higher as compared to healthy subjects. The entire cohort was then divided into tertiles of age: at rest, no significant differences were recorded for each age group between hypertensives and normotensives except for E/E' that was higher in hypertensives. At peak exercise, hypertensives had higher pulmonary artery systolic pressure (PASP) and E/E' but lower tricuspid annular plane systolic excursion (TAPSE) as age increased, compared to normotensives. Differences in E/E' and TAPSE between the 2 groups at peak exercise were explained by the interaction between HTN and age even after adjustment for baseline values (p < 0.001 for E/E', p = 0.011 for TAPSE). At peak exercise, the oldest group of hypertensive patients had a mean E/E' of 13.0, suggesting a significant increase in LV diastolic pressure combined with increased PASP. CONCLUSION: Age and HTN have a synergic negative effect on E/E' and TAPSE at peak exercise in hypertensive subjects.

Reference Ranges of Left Ventricular Hemodynamic Forces in Healthy Adults: A Speckle-Tracking Echocardiographic Study.

BACKGROUND: The normal limits of left ventricular (LV) hemodynamic forces (HDFs) are not exactly known. The aim of this study was to explore the full spectrum of HDF parameters in healthy subjects and determine their physiologic correlates. METHODS: 269 healthy subjects were enrolled (mean age: 43 ± 14 years; 123 (45.7%) men). All participants underwent an echo-Doppler examination. Tri-plane tissue tracking from apical views was used to measure 2D global endocardial longitudinal strain (GLS), circumferential strain (GCS), and LV HDFs. HDFs were normalized with LV volume and divided by specific weight. RESULTS: LV systolic longitudinal HDFs (%) were higher in men (20.8 ± 6.5 vs. 18.9 ± 5.6, p = 0.009; 22.0 ± 6.7 vs. 19.8 ± 5.6, p = 0.004, respectively). There was a significant correlation between GCS (increased) (r = -0.240, p < 0.001) and LV longitudinal HDFs (reduced) (r = -0.155, p = 0.01) with age. In a multivariable analysis age, BSA, pulse pressure, heart rate and GCS were the only independent variables associated with LV HDFs (ß coefficient = -0.232, p < 0.001; 0.149, p = 0.003; 0.186, p < 0.001; 0.396, p < 0.001; -0.328, p < 0.001; respectively). CONCLUSION: We report on the physiologic range of LV HDFs. Knowledge of reference values of HDFs may prompt their implementation into clinical routine and allow a more comprehensive assessment of the LV function.

A New Era of Diagnosis and Therapy in Acute Aortic Syndromes: The Mainz-Essen Experience (Part II)-Management and Outcomes.

Over the years, the cardiovascular department of Johannes Gutenberg University in Mainz-West-German Heart Centre in Essen (Germany) designed and implemented the hybrid operating room (2003) along with advanced endovascular and surgical procedures, including the frozen elephant trunk technique. For the study purpose, the Mainz-Essen experience on acute aortic syndromes was summarized by considering original articles from single-center or multicenter studies performed at West German Heart Centre, Essen, Germany, or at the cardiovascular department of Johannes Gutenberg University, Mainz, Germany. We present the 35-year-long Mainz-Essen research, education, and patient management journey in creating an integrated multidisciplinary "Aortic Center" in the heart of Europe.