The Role of Cardiopulmonary Exercise Testing in Hypertrophic Cardiomyopathy.

This review emphasizes the importance of cardiopulmonary exercise testing (CPET) in patients diagnosed with hypertrophic cardiomyopathy (HCM). In contrast to standard exercise testing and stress echoes, which are limited due to the ECG changes and wall motion abnormalities that characterize this condition, CPET allows for the assessment of the complex pathophysiology and severity of the disease, its mechanisms of functional limitation, and its risk stratification. It is useful tool to evaluate the risk for sudden cardiac death and select patients for cardiac resynchronization therapy (CRT), cardiac transplantation, or mechanical circulatory support, especially when symptomatology and functional status are uncertain. It may help in differentiating HCM from other forms of cardiac hypertrophy, such as athletes' heart. Finally, it is used to guide and monitor therapy as well as for exercise prescription. It may be considered every 2 years in clinically stable patients or every year in patients with worsening symptoms. Although performed only in specialized centers, CPET combined with echocardiography (i.e., CPET imaging) and invasive CPET are more informative and provide a better assessment of cardiac functional status, left ventricular outflow tract obstruction, and diastolic dysfunction during exercise in patients with HCM.

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.

Physiological behavior during stress anticipation across different chronic stress exposure adaptive models.

Anticipation of stress induces physiological, behavioral and cognitive adjustments that are required for an appropriate response to the upcoming situation. Additional research examining the response of cardiopulmonary parameters and stress hormones during anticipation of stress in different chronic stress adaptive models is needed. As an addition to our previous research, a total of 57 subjects (16 elite male wrestlers, 21 water polo player and 20 sedentary subjects matched for age) were analyzed. Cardiopulmonary exercise testing (CPET) on a treadmill was used as the laboratory stress model; peak oxygen consumption (VO2) was obtained during CPET. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol, alpha-melanocyte stimulating hormone (alpha-MSH) and N-terminal-pro-B type natriuretic peptide (NT-pro-BNP) were measured by radioimmunometric, radioimmunoassay and immunoassay sandwich technique, respectively, together with cardiopulmonary measurements, 10 minutes pre-CPET and at the initiation of CPET. The response of diastolic blood pressure and heart rate was different between groups during stress anticipation (p = 0.019, 0.049, respectively), while systolic blood pressure, peak VO2 and carbon-dioxide production responses were similar. ACTH and cortisol increased during the experimental condition, NT-pro-BNP decreased and alpha-MSH remained unchanged. All groups had similar hormonal responses during stress anticipation with the exception of the ACTH/cortisol ratio. In all three groups, ΔNT-pro-BNP during stress anticipation was the best independent predictor of peak VO2 (B = 36.01, r = 0.37, p = 0.001). In conclusion, the type of chronic stress exposure influences the hemodynamic response during anticipation of physical stress and the path of hormonal stress axis activation. Stress hormones released during stress anticipation may hold predictive value for overall cardiopulmonary performance during the stress condition.

LAY SUMMARYThe study revealed differences in hormonal and hemodynamic responses during anticipation of stress between athletes and sedentary participants. Stress hormones released during stress anticipation may hold predictive value for overall cardiopulmonary performance during the stress condition.

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.

Systemic and Ophthalmic Manifestations in Different Types of Refractive Errors in Patients with Down Syndrome.

Background and Objective: This study aims to investigate the prevalence of systemic and ophthalmic manifestations in different refractive groups in children and young adults with Down syndrome (DS). Materials and Methods: The study was a population-based, cross-sectional study that included 141 Caucasian children and young adults with DS. They were classified into the following three groups: myopia DS group (37 subjects, mean age 15.8 years), emmetropia DS group (41 subjects, mean age 11.7 years) and hyperopia DS group (63 subjects, mean age 10.9 years). The participants underwent inspection, slit-lamp examination, cycloplegic refraction, ocular alignment and ocular motility examination. Ten systemic manifestations were analyzed. Results: There was no difference in the prevalence of any systemic manifestations between the groups. Considering the ophthalmic manifestations, there was statistical difference in the distribution of proportions among the three groups for nystagmus (p = 0.011), iris-stromal atrophy (p = 0.048) and strabismus (p = 0.031). The prevalence of strabismus in our DS myopia group was 35.1%, and in DS hyperopia group 38.1%. Conclusions: The results of our study suggest that DS children and young adults with any refractive error do not have a higher chance of additional systemic manifestations. Myopia in DS was associated with a higher prevalence of nystagmus and iris stromal atrophy, whereas astigmatism was found to be more frequent in hyperopia.

Randomized Controlled Comparison of Optimal Medical Therapy with Percutaneous Recanalization of Chronic Total Occlusion (COMET-CTO).

The aim of this randomized prospective study was to evaluate the quality of life (QoL) using the "Seattle Angina Questionnaire" (SAQ) in patients with chronic total occlusion (CTO) in coronary arteries treated with either percutaneous coronary intervention (PCI) or optimal medical therapy (OMT), or only with OMT.The potential benefits of recanalization of CTO by PCI have been controversial because of the scarcity of randomized controlled trials.A total of 100 patients with CTO were randomized (1:1) prospectively into the PCI CTO or the OMT group (50 patients in each group). There were no baseline differences in the SAQ scores between the groups, except for physical limitation scores (P = 0.03). During the mean follow-up (FUP) of 275 ± 88 days, patients in the PCI group reported less physical activity limitations (72.7 ± 21.3 versus 60.5 ± 27, P = 0.014), less frequent angina episodes (89.8 ± 17.6 versus 76.8 ± 27.1, P = 0.006), better QoL (79.9 ± 22.7 versus 62.5 ± 25.5, P = 0.001), greater treatment satisfaction (91.2 ± 13.6 versus 81.4 ± 18.4, P = 0.003), and borderline differences in angina stability (61.2 ± 26.5 versus 51.0 ± 23.7, P = 0.046) compared to patients in the OMT group. There were no significant differences in SAQ scores in the OMT group at baseline and during the FUP. There was a statistically significant increase in all five domains in the PCI group.Symptoms and QoL measured by the SAQ were significantly improved after CTO PCI compared to OMT alone.

Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and ß-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations. METHODS: As a part of the international multidisciplinary SILICOFCM project ( www.silicofcm.eu ) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography. RESULTS: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p = 0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p = 0.085). Laboratory analyses revealed normal levels of creatinine (85.5 ± 18.3 vs. 81.3 ± 16.4 µmol/l; p = 0.487) and blood urea nitrogen (10.2 ± 15.6 vs. 6.9 ± 3.9 mmol/l; p = 0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p = 0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p = 0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p = 0.001). The difference in diastolic function, i.e. E/e' ratio between the two groups was also noted (MYBPC3 8.8 ± 3.3, MYH7 13.9 ± 6.9, p = 0.079). CONCLUSIONS: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

Prompt and consistent improvement of coronary flow velocity reserve following successful recanalization of the coronary chronic total occlusion in patients with viable myocardium.

BACKGROUND: Coronary chronic total occlusion (CTO) is characterized by the presence of collateral blood vessels which can provide additional blood supply to CTO-artery dependent myocardium. Successful CTO recanalization is followed by significant decrease in collateral donor artery blood flow and collateral derecruitment, but data on coronary hemodynamic changes in relation to myocardial function are limited. We assessed changes in coronary flow velocity reserve (CFVR) by echocardiography in collateral donor and recanalized artery following successful opening of coronary CTO. METHODS: Our study enrolled 31 patients (60 ± 9 years; 22 male) with CTO and viable myocardium by SPECT scheduled for percutaneous coronary intervention (PCI). Non-invasive CFVR was measured in collateral donor artery before PCI, 24 h and 6 months post-PCI, and 24 h and 6 months in recanalized artery following successful PCI of CTO. RESULTS: Collateral donor artery showed significant increase in CFVR 24 h after CTO recanalization compared to pre-PCI values (2.30 ± 0.49 vs. 2.71 ± 0.45, p = 0.005), which remained unchanged after 6-months (2.68 ± 0.24). Baseline blood flow velocity of the collateral donor artery significantly decreased 24 h post-PCI compared to pre-PCI (0.28 ± 0.06 vs. 0.24 ± 0.04 m/s), and remained similar after 6 months, with no significant difference in maximum hyperemic blood flow velocity pre-PCI, 24 h and 6 months post-PCI. CFVR of the recanalized coronary artery 24 h post-PCI was 2.55 ± 0.35, and remained similar 6 months later (2.62 ± 0.26, p = NS). CONCLUSIONS: In patients with viable myocardium, prompt and significant CFVR increase in both recanalized and collateral donor artery, was observed within 24 h after successful recanalization of CTO artery, which maintained constant during the 6 months. TRIAL REGISTRATION: ClinicalTrials.gov (Number NCT04060615 ).

Improved Propensity-Score Matched Long-Term Clinical Outcomes in Patients with Successful Percutaneous Coronary Interventions of Coronary Chronic Total Occlusion.

The objective of the study was to evaluate major adverse cardiovascular events (MACE) after successful versus failed percutaneous coronary intervention for chronic total occlusion (PCI-CTO).Limited data are available on long-term clinical follow-up in the treatment of chronic total occlusion (CTO).Between January 2009 and December 2010 PCI-CTO was attempted in 283 consecutive patients with 289 CTO lesions. Procedural success was 62.3% and clinical follow-up covered 83% (235/283) of the study population with a median follow-up of 66 months (range, 59-74).The total incidence of MACE was 57/235 (24.3%), and was significantly higher in the procedural failure group than in the procedural success group (33/87 (37.9%) versus 24/148 (16.2%), P < 0.001). All-cause mortality was significantly lower in patients with successful PCI-CTO compared to failed PCI-CTO (10.8% versus 20.7%, P < 0.05). Also, the rate of cardiovascular death in the procedural failure group (14.9%) was slightly higher than that in the procedural success group (7.4%, P = 0.066). The rate of TVR was statistically higher in the procedural failure group (P < 0.009). Propensity score-adjusted Cox regression showed that procedural success remained a significant predictor of MACE (adjusted HR 0.402; 95% CI 0.196-0.824; P = 0.013).Our study emphasizes the importance of CTO recanalization in improving long-term outcome including all-cause mortality with a borderline effect on cardiovascular mortality.

Prognostic value of calcium score and coronary flow velocity reserve in asymptomatic diabetic patients.

BACKGROUND: The risk stratification of patients with diabetes mellitus (DM) is a major objective for the clinicians, and it can be achieved by coronary flow velocity reserve (CFVR) or with coronary artery calcium score (CS). CS evaluates underlying coronary atherosclerotic plaque burden and CFVR estimates both presence of coronary artery stenosis and microvascular function. Consequently, CFVR may provide unique risk information beyond the extent of coronary atherosclerosis. AIM: Our aim is to assess joint prognostic value of CFVR and CS in asymptomatic DM patients. MATERIALS AND METHODS: We prospectively included 200 asymptomatic patients (45,5 % male, mean age 57,35 ± 11,25), out of which, there were 101 asymptomatic patients with DM and 99 asymptomatic patients without DM, but with one or more conventionally risk factors for coronary artery disease. We analyzed clinical, biochemical, metabolic, inflammatory parameters, CS by Agatston method, transthoracic Doppler echocardiography CFVR of left anterior descending artery and echocardiographic parameters. RESULTS: Total CS and CS LAD were significantly higher, while mean CFVR was lower in diabetics compared to the nondiabetics. During 1 year follow-up, 24 patients experienced cardio-vascular events (one cardiovascular death, two strokes, three myocardial infarctions, nine new onsets of unstable angina and nine myocardial revascularizations): 19 patients with DM and five non DM patients, (p = 0,003). Overall event free survival was significantly higher in non DM group, compared to the DM group (94,9 % vs. 81,2 %, p = 0,002 respectively), while the patients with CS ≥200 and CFVR <2 had the worst outcome during 1 year follow up in the whole study population as well as in the DM group. At multivariable analysis CFVR on LAD (HR 12.918, 95 % CI 3.865-43.177, p < 0.001) and total CS (HR 13.393, 95 % CI 1.675-107.119, p = 0.014) were independent prognostic predictors of adverse events in DM group of patients. CONCLUSION: Both CS and CFVR provide independent and complementary prognostic information in asymptomatic DM patients. When two parameters are analyzed together, the risk stratification ability improves, even when DM patients are analyzed together with non DM patients. As a result, DM patients with CS ≥200 and CFVR <2 had the worst outcome. Consequently, the use of two tests identified subset of patients who can derive the most benefit from the intensive prevention measures.

The effects of nicorandil on microvascular function in patients with ST segment elevation myocardial infarction undergoing primary PCI.

BACKGROUND: Nicorandil, as a selective potassium channel opener, has dual action including coronary and peripheral vasodilatation and cardioprotective effect through ischemic preconditioning. Considering those characteristics, nicorandil was suggested to reduce the degree of microvascular dysfunction. METHODS: Thirty-two patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI) were included in the study. Index of microvascular resistance (IMR) was measured in all patients immediatelly after pPCI before the after administration of Nicorandil. ST segment resolution was monitored before intervention and 60 min after terminating the procedure. Echocardiographic evaluation of myocardial function and transthoracic Doppler derived Coronary flow reserve (CFR) of infarct related artery (IRA) was performed during hospitalization and 3 months later. RESULTS: IMR was significantly lower after administration of Nicorandil (9.9 ± 3.7 vs. 14.1 ± 5.1, p < 0.001). There was significant difference in ST segment elevation before and after primary PCI with administration of Nicorandil (6.9 ± 3.7 mm vs. 1.6 ± 1.6 mm, p < 0.001). Transthoracic Doppler CFR measurement improved after 3 months (2.69 ± 0.38 vs. 2.92 ± 0.54, p = 0.021), as well as WMSI (1.14 ± 0.17 vs. 1.07 ± 0.09, p = 0.004). CONCLUSION: Intracoronary Nicorandil administration after primary PCI significantly decreases IMR, resulting in improved CFR and ventricular function in patients with STEMI undergoing primary PCI.

Acute insulin resistance in ST-segment elevation myocardial infarction in non-diabetic patients is associated with incomplete myocardial reperfusion and impaired coronary microcirculatory function.

BACKGROUND: Insulin resistance (IR) assessed by the Homeostatic Model Assessment (HOMA) index in the acute phase of myocardial infarction in non-diabetic patients was recently established as an independent predictor of intrahospital mortality. In this study we postulated that acute IR is a dynamic phenomenon associated with the development of myocardial and microvascular injury and larger final infarct size in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI). METHODS: In 104 consecutive patients with the first anterior STEMI without diabetes, the HOMA index was determined on the 2nd and 7th day after pPCI. Worst-lead residual ST-segment elevation (ST-E) on postprocedural ECG, coronary flow reserve (CFR) determined by transthoracic Doppler echocardiography on the 2nd day after pPCI and fixed perfusion defect on single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) determined six weeks after pPCI were analyzed according to HOMA indices. RESULTS: IR was present in 55 % and 58 % of patients on day 2 and day 7, respectively. Incomplete post-procedural ST-E resolution was more frequent in patients with IR compared to patients without IR, both on day 2 (p = 0.001) and day 7 (p < 0.001). The HOMA index on day 7 correlated with SPECT-MPI perfusion defect (r = 0.331), whereas both HOMA indices correlated well with CFR (r = -0.331 to -0.386) (p < 0.01 for all). In multivariable backward logistic regression analysis adjusted for significant univariate predictors and potential confounding variables, IR on day 2 was an independent predictor of residual ST-E ≥ 2 mm (OR 11.70, 95% CI 2.46-55.51, p = 0.002) and CFR < 2 (OR = 5.98, 95% CI 1.88-19.03, p = 0.002), whereas IR on day 7 was an independent predictor of SPECT-MPI perfusion defect > 20% (OR 11.37, 95% CI 1.34-96.21, p = 0.026). CONCLUSION: IR assessed by the HOMA index during the acute phase of the first anterior STEMI in patients without diabetes treated by pPCI is independently associated with poorer myocardial reperfusion, impaired coronary microcirculatory function and potentially with larger final infarct size.

The randomized physiologic assessment of thrombus aspiration in patients with acute ST-segment elevation myocardial infarction trial (PATA STEMI): study rationale and design.

INTRODUCTION: Routine thrombus aspiration is proposed to be superior to conventional primary percutaneous coronary intervention (PCI) in terms of improved myocardial perfusion, in patients with ST-segment elevation acute myocardial infarction (STEMI). However, myocardial perfusion after thrombus aspiration has not been evaluated by a quantitative, invasive method. We intend to determine whether manual thrombus aspiration in the infarct-related coronary artery increases myocardial perfusion assessed by index of microcirculatory resistance (IMR) compared with conventional primary PCI. STUDY DESIGN: PATA STEMI is a single-center, prospective, randomized trial with a planned inclusion of 128 patients with the first STEMI. Prior to coronary angiography, patients are randomly assigned to thrombus aspiration using the Eliminate aspiration catheter (Terumo Medical Supply, Japan) or to conventional primary PCI. After completion of primary PCI, IMR is determined both in infarct-related artery and in noninfarct-related arteries without critical stenoses. The primary end-point is a group mean value of IMR after thrombus aspiration compared with conventional primary PCI. Secondary end-points are myocardial perfusion grade, resolution of ST-segment elevation, enzymatic estimation of infarct size, left ventricular remodeling assessed by echocardiographic indices, and major adverse cardiac events rate at 1, 6, and 12 months. CONCLUSION: If manual thrombus aspiration significantly reduces microcirculatory resistance, thereby improving myocardial perfusion, it may become the routine strategy in primary PCI.

The role of glycemia in acute heart failure patients.

Acute heart failure (AHF) is one of the most important cardiovascular syndromes associated with high cardiovascular morbidity, and is the major cause of admission in emergency departments worldwide. The clinical complexity of AHF has significantly increased, mostly due to the comorbidities: diabetes, arterial hypertension, dyslipidemia, obesity, peripheral vascular disease, renal insufficiency and anemia. Numerous clinical trials have demonstrated a frequent association of AHF and diabetes. Since AHF is a very heterogeneous condition, it is important to identify clinical and laboratory parameters useful for risk stratification of these populations. Hyperglycemia may be one of the most convenient, since it is widely measured, easily interpreted, and inexpensive. Acute coronary syndrome (ACS), arrhythmias and poor compliance to chronic medications are considered to be the most frequent precipitating factors of AHF in diabetics. Several studies identified diabetes as the most prominent independent predictor of morbidity and mortality in both acute and chronic heart failure (HF) patients. The following parameters were identified as the independent predictors of in-hospital mortality in patients with AHF and diabetes: older age, systolic blood pressure <100 mmHg, ACS, non-compliance, history of hypertension, left ventricular ejection fraction (LVEF) <50%, serum creatinine >1.5 mg/dL, marked elevation of natriuretic peptides, hyponatremia, treatment at admission without ACE inhibitors/ARBs/ß-blockers, and no percutaneous coronary intervention (PCI) as a treatment modality. The most frequent cause of AHF is ACS, both with ST segment elevation (STEMI) or without (NSTEMI). Hyperglycemia is very common in these patients and although frequently unrecognized and untreated, has a large in-hospital and mortality significance.

Structural myocardial alterations in diabetes and hypertension: the role of galectin-3.

BACKGROUND: Galectin-3 is a protein widely distributed in the heart, brain and blood vessels, and has a regulatory role in inflammation, immunology and cancer. Many studies demonstrated that the increased level of galectin-3 is associated with progressive fibrosis and stiffening of the myocardium. The aim of this study was to investigate the role of galectin-3 in patients with type 2 diabetes (T2D) and/or arterial hypertension (HT). METHODS: Study population included 189 patients, with no coronary artery disease, divided into three groups: group 1 (T2D), group 2 (T2D+HT), and group 3 (HT). All subjects underwent routine laboratory tests, as well as specific biomarkers assessment [galectin-3, glycosylated hemoglobin (HbA1c), N- terminal fragment B-type natriuretic peptide (NT-proBNP)]. Cardiological evaluation included physical examination, transthoracic tissue Doppler echocardiography and stress echocardiography. RESULTS: The results of this study demonstrated significantly increased levels of galectin-3, blood glucose, and HbA1c in group 2. Also, echocardiographicaly, left ventricular (LV) diameters and IVS thickness were increased in this group of patients. Furthermore, in the same cohort a positive correlation between galectin-3 and NT-pro BNP, and galectin-3 and LV mass were demonstrated. In addition, a negative correlation between galectin-3 and LV end-diastolic diameter was revealed. CONCLUSIONS: This study revealed that levels of galectin-3 were higher in patients with both T2D and HT, and correlated with LV mass, indicating the potential role of this biomarker for early detection of myocardial structural and functional alterations.

Noninvasive evaluation of dynamic microvascular dysfunction in ischemia and no obstructive coronary artery disease patients with suspected vasospasm.

INTRODUCTION: In patients with ischemia and no obstructive coronary artery disease (INOCA), a dynamic coronary microvascular dysfunction (CMD) is frequent but difficult to capture by noninvasive means.The aim of our study was to assess dynamic CMD in INOCA patients with stress echocardiography after vasoconstrictive and vasodilator stimuli. METHODS: In this prospective single-center study, we have enrolled 40 INOCA patients (age 56.3 ±â€Š13 years, 32 women). All participants underwent stress echocardiography with hyperventilation (HYP), followed by supine bicycle exercise (HYP+EXE) and adenosine (ADO). Stress echocardiography included an assessment of regional wall motion abnormality (RWMA) and coronary flow velocity (CFV) in the distal left anterior descending (LAD) coronary artery. RESULTS: HYP induced a 30% increase in rate pressure product (rest = 10 244 ±â€Š2353 vs. HYP = 13 214 ±â€Š3266 mmHg x bpm, P  < 0.001) accompanied by a paradoxical reduction in CFV (HYP< rest) in 21 patients (52%). HYP alone was less effective than HYP+EXE in inducing anginal pain (6/40, 15% vs. 10/40, 25%, P  = 0.046), ST segment changes (6/40, 15% vs. 24/40, 60%, P  < 0.001), and RWMA (6/40, 15% vs. 13/40, 32.5%, P  = 0.008). ADO-induced vasodilation was preserved (≥2.0) in all patients. CONCLUSION: In patients with INOCA, a coronary vasoconstriction after HYP is common, in absence of structural CMD detectable with ADO. HYP+EXE test represents a more powerful ischemia inducer than HYP alone. Stress echocardiography with LAD-CFV may allow the noninvasive assessment of dynamic and structural coronary microcirculation during stress.

Sacubitril/valsartan for the treatment of non-obstructive hypertrophic cardiomyopathy: An open label randomized controlled trial (SILICOFCM).

AIM: Sacubitril/valsartan treatment reduces mortality and hospitalizations in heart failure with reduced ejection fraction but has limited application in hypertrophic cardiomyopathy (HCM). The aim of this study was to evaluate the effect of sacubitril/valsartan on peak oxygen consumption (VO2) in patients with non-obstructive HCM. METHODS AND RESULTS: This is a phase II, randomized, open-label multicentre study that enrolled adult patients with symptomatic non-obstructive HCM (New York Heart Association class I-III) who were randomly assigned (2:1) to receive sacubitril/valsartan (target dose 97/103 mg) or control for 16 weeks. The primary endpoint was a change in peak VO2. Secondary endpoints included echocardiographic measures of cardiac structure and function, natriuretic peptides and other cardiac biomarkers, and Minnesota Living with Heart Failure quality of life. Between May 2018 and October 2021, 354 patients were screened for eligibility, 115 patients (mean age 58 years, 37% female) met the study inclusion criteria and were randomly assigned to sacubitril/valsartan (n = 79) or control (n = 36). At 16 weeks, there was no significant change in peak VO2 from baseline in the sacubitril/valsartan (15.3 [4.3] vs. 15.9 [4.3] ml/kg/min, p = 0.13) or control group (p = 0.47). No clinically significant changes were found in blood pressure, cardiac structure and function, plasma biomarkers, or quality of life. CONCLUSION: In patients with HCM, a 16-week treatment with sacubitril/valsartan was well tolerated but had no effect on exercise capacity, cardiac structure, or function.