Treatment of severe symptomatic aortic valve stenosis using non-invasive ultrasound therapy: a cohort study.

BACKGROUND: Calcific aortic stenosis is commonly treated using surgical or transcatheter aortic valve replacement; however, many patients are not considered suitable candidates for these interventions due to severe comorbidities and limited life expectancy. As such, non-invasive therapies might offer alternative therapeutic possibilities in these patients. This study aimed to assess the safety of non-invasive ultrasound therapy and its ability to improve valvular function by softening calcified valve tissue. METHODS: This prospective, multicentre, single-arm series enrolled 40 adult patients with severe symptomatic aortic valve stenosis at three hospitals in France, the Netherlands, and Serbia between March 13, 2019, and May 8, 2022. Patients were treated with transthoracically delivered non-invasive ultrasound therapy. Follow-ups were scheduled at 1, 3, 6, 12, and 24 months. The primary endpoints were procedure-related deaths within 30 days and improved valve function. We report the 6-month data. This study is registered at ClinicalTrials.gov, NCT03779620 and NCT04665596. FINDINGS: 40 high-risk patients with a mean Society of Thoracic Surgeons score of 5·6% (SD 4·4) and multiple severe comorbidities were included. The primary endpoint, procedure-related mortality, did not occur; furthermore, no life-threatening or cerebrovascular events were reported. Improved valve function was confirmed up to 6 months, reflected by a 10% increase in mean aortic valve area from 0·58 cm2 (SD 0·19) at baseline to 0·64 cm2 (0·21) at follow-up (p=0·0088), and a 7% decrease in mean pressure gradient from 41·9 mm Hg (20·1) to 38·8 mm Hg (17·8; p=0·024). At 6 months, the New York Heart Association score had improved or stabilised in 24 (96%) of 25 patients, and the mean Kansas City Cardiomyopathy Questionnaire score had improved by 33%, from 48·5 (SD 22·6) to 64·5 (21·0). One serious procedure-related adverse event occurred in a patient who presented with a transient decrease in peripheral oxygen saturation. Non-serious adverse events included pain, discomfort during treatment, and transient arrhythmias. INTERPRETATION: This novel, non-invasive ultrasound therapy for calcified aortic stenosis proved to be safe and feasible. FUNDING: Cardiawave.

Perivascular adipose tissue as a source of therapeutic targets and clinical biomarkers.

Obesity is a modifiable cardiovascular risk factor, but adipose tissue (AT) depots in humans are anatomically, histologically, and functionally heterogeneous. For example, visceral AT is a pro-atherogenic secretory AT depot, while subcutaneous AT represents a more classical energy storage depot. Perivascular adipose tissue (PVAT) regulates vascular biology via paracrine cross-talk signals. In this position paper, the state-of-the-art knowledge of various AT depots is reviewed providing a consensus definition of PVAT around the coronary arteries, as the AT surrounding the artery up to a distance from its outer wall equal to the luminal diameter of the artery. Special focus is given to the interactions between PVAT and the vascular wall that render PVAT a potential therapeutic target in cardiovascular diseases. This Clinical Consensus Statement also discusses the role of PVAT as a clinically relevant source of diagnostic and prognostic biomarkers of vascular function, which may guide precision medicine in atherosclerosis, hypertension, heart failure, and other cardiovascular diseases. In this article, its role as a 'biosensor' of vascular inflammation is highlighted with description of recent imaging technologies that visualize PVAT in clinical practice, allowing non-invasive quantification of coronary inflammation and the related residual cardiovascular inflammatory risk, guiding deployment of therapeutic interventions. Finally, the current and future clinical applicability of artificial intelligence and machine learning technologies is reviewed that integrate PVAT information into prognostic models to provide clinically meaningful information in primary and secondary prevention.

Prognostic Value of Mitral Regurgitation in Patients with Primary Hypertrophic Cardiomyopathy.

Background and Objectives: Mitral valve pathology and mitral regurgitation (MR) are very common in patients with hypertrophic cardiomyopathy (HCM), and the evaluation of mitral valve anatomy and degree of MR is important in patients with HCM. The aim of our study was to examine the potential influence of moderate or moderately severe MR on the prognosis, clinical presentation, and structural characteristics of HCM patients. Materials and Methods: A prospective study examined 176 patients diagnosed with primary asymmetric HCM. According to the severity of the MR, the patients were divided into two groups: Group 1 (n = 116) with no/trace or mild MR and Group 2 (n = 60) with moderate or moderately severe MR. All patients had clinical and echocardiographic examinations, as well as a 24 h Holter ECG. Results: Group 2 had significantly more often the presence of the obstructive type of HCM (p < 0.001), syncope (p = 0.030), NYHA II class (p < 0.001), and atrial fibrillation (p = 0.023). Also, Group 2 had an enlarged left atrial dimension (p < 0.001), left atrial volume index (p < 0.001), and indirectly measured systolic pressure in the right ventricle (p < 0.001). Patients with a higher grade of MR had a significantly higher E/e' (p < 0.001) and, as a result, higher values of Nt pro BNP values (p < 0.001) compared to Group 1. Kaplan-Meier analysis demonstrated that the event-free survival rate during a median follow-up of 88 (IQR 40-112) months was significantly higher in Group 1 compared to Group 2 (84% vs. 45% at 8 years; log-rank 20.4, p < 0.001). After adjustment for relevant confounders, the presence of moderate or moderately severe MR remained as an independent predictor of adverse outcomes (HR 2.788; 95% CI 1.221-6.364, p = 0.015). Conclusions: The presence of moderate or moderately severe MR was associated with unfavorable long-term outcomes in HCM patients.

The basic heart anatomy and physiology from the cardiologist's perspective: Toward a better understanding of left ventricular mechanics, systolic, and diastolic function.

A comprehensive understanding of the cardiac structure-function relationship is essential for proper clinical cardiac imaging. This review summarizes the basic heart anatomy and physiology from the perspective of a heart imager focused on myocardial mechanics. The main issues analyzed are the left ventricular (LV) architecture, the LV myocardial deformation through the cardiac cycle, the LV diastolic function basic parameters and the basic parameters of the LV deformation used in clinical practice for the LV function assessment.

Multimodality imaging for the management of patients with primary mitral regurgitation.

Advanced cardiac imaging (ACI), including myocardial deformation imaging, 3D echocardiography and cardiac magnetic resonance, overcomes the limitations of conventional echocardiography in the assessment of patients with primary mitral regurgitation (MR). They enable a more precise MR quantification and reveal early changes before advanced and irreversible remodeling with depressed heart function occurs. ACI permits a thorough analysis of mitral valvular anatomy and MR mechanisms (important for planning and guiding percutaneous and surgical procedures) and helps to identify structural and functional changes coupled with a high arrhythmogenic potential, especially the occurrence of atrial fibrillation and heart failure development. The key question is how the data provided by ACI can improve the current management of primary MR.

Role of different echocardiographic modalities in the assessment of microvascular function in women with ischemia and no obstructive coronary arteries.

This review summarizes current knowledge about echocardiographic modalities used to assess microvascular function and left ventricular (LV) systolic function in women with ischemia and no obstructive coronary arteries (INOCA). Although the entire pathophysiological background of this clinical entity still remains elusive, it is primarily linked to microvascular dysfunction which can be assessed by coronary flow velocity reserve. Subtle impairments of LV systolic function in women with INOCA are difficult to assess by interpretation of wall motion abnormalities. LV longitudinal function impairment is considered to be an early marker of subclinical systolic dysfunction and can be assessed by global longitudinal strain quantification.

Does Atrial Fibrillation at Diagnosis Change Prognosis in Patients with Aortic Stenosis?

Background: Aortic stenosis (AS) is a common valve disease and atrial fibrillation (AF) is the most common cardiac arrhythmia, frequently associated with AS. This study aimed to evaluate the impact of AF on mortality in patients with moderate and severe AS. Methods: We retrospectively analyzed 1070 consecutive moderate and severe AS patients (57% were male, age was 69 ± 10, severe AS 22.5%), who underwent transthoracic echocardiography from March 2018 to November 2021. AS severity was defined by specific threshold values with severe AS being defined by a peak velocity > 4 m/s, an MPG > 40 mmHg, and an AVA < 1 cm2 and moderated by a peak velocity of 3-4 m/s, an MPG 20-40 mmHg and an AVA 1-1.5 cm. Patients with AF were defined as those having a history of AF when AS was found on the index echocardiography. The follow-up assessment in December 2023 ascertained vital status and data on aortic valve replacement (AVR). Results: 790 (73.8%) patients were with sinus rhythm (SR) and 280 (26.2%) patients with AF. Mortality was higher in patients with AF than in those with SR (46% vs. 36.2% HR 1.424, 95% CI 1.121-1.809, p = 0.004). After adjusting for clinical confounders, mortality risk in AF relative to SR remained significant (HR 1.284, 95% CI 1.03-1.643, p = 0.047). Patients with AF demonstrated high mortality risk in the moderate aortic stenosis stratum (HR 1.376, 95% CI 1.059-1.788, p = 0.017), with even greater risk in the severe AS stratum (HR 1.644, 95% CI 1.038-2.603, p = 0.034) with significant interaction (p = 0.007). In patients with AF AVR demonstrated a protective effect on survival (HR 0.365, 95% CI 0.202-0.627, p < 0.001), but to a lesser degree than in patients with sinus rhythm (HR 0.376, 95% CI 0.250-0.561, p < 0.001) without significant interaction (p = 0.278). In patients with AF mortality risk was high in the conservative treatment stratum (HR 1.361, 95% CI 1.066-1.739, p = 0.014), in the AVR stratum mortality risk was higher but did not reach statistical significance (HR 1.823, 95% CI 0.973-3.414, p = 0.061). However, when corrected for echocardiographic variables strongly correlated with AF, AF was no longer independently associated with all-cause mortality. (HR 0.97 95% CI 0.709-1.323, p = 0.84). Conclusions: Patients with moderate and severe AS and AF have worse prognosis than patients with SR which can be explained by cardiac damage. AVR improves survival in patients with AF and with SR.

Non-Invasive Ultrasound Therapy for Severe Aortic Stenosis: Early Effects on the Valve, Ventricle, and Cardiac Biomarkers (A Case Series).

Background: Transcatheter aortic valve replacement (TAVR) was developed for inoperable patients with severe aortic stenosis. However, despite TAVR advancements, some patients remain untreated due to complex comorbidities, necessitating less-invasive approaches. Non-invasive ultrasound therapy (NIUT), a new treatment modality, has the potential to address this treatment gap, delivering short ultrasound pulses that create cavitation bubble clouds, aimed at softening embedded calcification in stiffened valve tissue. Methods: In the prospective Valvosoft® Serbian first-in-human study, we assessed the safety and efficacy of NIUT and its impact on aortic valve hemodynamics, on the left ventricle, and on systemic inflammation in patients with severe symptomatic aortic stenosis not eligible for TAVR or surgery. Results: Ten patients were included. Significant improvements were observed in hemodynamic parameters from baseline to one month, including a 39% increase in the aortic valve area (from 0.5 cm2 to 0.7 cm2, p = 0.001) and a 23% decrease in the mean transvalvular gradient (from 54 mmHg to 38 mmHg, p = 0.01). Additionally, left ventricular global longitudinal strain significantly rose, while global wasted work significantly declined at one month. A dose-response relationship was observed between treatment parameters (peak acoustic power, intensity spatial-peak pulse-average, and mean acoustic energy) and hemodynamic outcomes. NIUT was safely applied, with no clinically relevant changes in high-sensitivity troponin T or C-reactive protein and with a numerical, but not statistically significant, reduction in brain natriuretic peptide (from 471 pg/mL at baseline to 251 pg/mL at one month). Conclusions: This first-in-human study demonstrates that NIUT is safe and confers statistically significant hemodynamic benefits both on the valve and ventricle.

Correlation of Non-Invasive Transthoracic Doppler Echocardiography with Invasive Doppler Wire-Derived Coronary Flow Reserve and Their Impact on Infarct Size in Patients with ST-Segment Elevation Myocardial Infarction Treated with Primary Percutaneous Coronary Intervention.

Background: Coronary microvascular dysfunction is associated with adverse prognosis after ST-segment elevation myocardial infarction (STEMI). We aimed to compare the invasive, Doppler wire-based coronary flow reserve (CFR) with the non-invasive transthoracic Doppler echocardiography (TTDE)-derived CFR, and their ability to predict infarct size. Methods: We included 36 patients with invasive Doppler wire assessment on days 3-7 after STEMI treated with primary percutaneous coronary intervention (PCI), of which TTDE-derived CFR was measured in 47 vessels (29 patients) within 6 h of the invasive Doppler. Infarct size was assessed by cardiac magnetic resonance at a median of 8 months. Results: The correlation between invasive and non-invasive CFR was modest in the overall cohort (rho 0.400, p = 0.005). It improved when only measurements in the LAD artery were considered (rho 0.554, p = 0.002), with no significant correlation in the RCA artery (rho -0.190, p = 0.435). Both invasive (AUC 0.888) and non-invasive (AUC 0.868) CFR, measured in the recanalized culprit artery, showed a good ability to predict infarct sizes ≥18% of the left ventricular mass, with the optimal cut off values of 1.85 and 1.80, respectively. Conclusions: In patients with STEMI, TTDE- and Doppler wire-derived CFR exhibit significant correlation, when measured in the LAD artery, and both have a similarly strong association with the final infarct size.

Case report: Acute toxic myocardial damage caused by 5-fluorouracil-from enigma to success.

Considering the pandemic of both cardiovascular diseases and oncological diseases, there is an increasing need for the use of chemotherapy, which through various pathophysiological mechanisms leads to damage to heart function. Cardio toxicity of chemotherapy drugs can manifest itself in a variety of clinical manifestations, which is why establishing a valid diagnosis is a real mystery for clinicians. Acute systolic heart failure (AHF) due to the use of 5-fluorouracil (5-FU) is a rare occurrence if it is not associated with myocardial infarction, myocarditis or Takotsubo cardiomyopathy. Therefore, we decided to present a case of an 52-year-old male who was diagnosed with stage IV RAS wild-type adenocarcinoma of the rectum and in whom the direct toxic effect 5-FU is the main reason for the appearance of toxic cardiomyopathy.

Cardiovascular disease and COVID-19: a consensus paper from the ESC Working Group on Coronary Pathophysiology & Microcirculation, ESC Working Group on Thrombosis and the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Heart Rhythm Association (EHRA).

The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as 'post-acute COVID-19' may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance.

[Pulsed Doppler tissue imaging in the early diagnosis of coronary artery disease].

INTRODUCTION: Cardiovascular diseases are the leading cause of death in the majority of well-developed countries. IMPORTANCE OF EARLY DIAGNOSIS: Early diagnosis of coronary artery disease is difficult due to blood vessels remodeling, late manifestations of reduced maximal and normal coronary blood flow, and negative correlation between stenosis and plaque burden. PULSED DOPPLER TISSUE IMAGING: Pulsed Doppler tissue imaging is used for assessment of myocardial velocity, whereas classical Doppler imaging is used for measurement of blood flow velocity. Systolic myocardial velocity profile During the systolic phase only a single myocardial motion is registered--S wave. DIASTOLIC MYOCARDIAL VELOCITY PROFILE: There are early and late myocardial relaxation velocities. Impact of coronary artery disease on myocardial velocities Early to late myocardial relaxation velocity ratio is influenced by coronary artery disease. This paper provides practical guidelines for using pulsed doppler tissue imaging. CONCLUSION: Pulsed Doppler tissue imaging is an excellent procedure for early diagnosis of coronary artery disease.