Coronary microvascular dysfunction affects left ventricular global longitudinal strain response to dipyridamole stress echocardiography: a pilot study.

The aim is to investigate, by means of speckle tracking echocardiography, left ventricular (LV) contractile function at rest and during dipyridamole stress in patients with coronary microvascular dysfunction (CMD). 59 patients (39% women, mean age 65.6 ± 6.1 years) with history of chest pain and without obstructive coronary artery disease (CAD) underwent dipyridamole stress echocardiography. Coronary flow was assessed in the left anterior descending coronary artery. Coronary flow reserve (CFR) was determined as the ratio of hyperaemic to baseline diastolic coronary flow velocity. CMD was defined as CFR < 2. Global longitudinal strain (GLS) was measured at rest and at peak dose. Nineteen patients (32%) among the overall population showed CMD. Baseline GLS was significantly lower in patients with CMD (- 16.8 ± 2.7 vs. - 19.1 ± 3.1, p < 0.01). A different contractile response to dipyridamole infusion was observed between the two groups: GLS significantly increased up to peak dose in patients without CMD (from - 19.1 ± 3.1 to - 20.2 ± 3.1, p < 0.01), and significantly decreased in patients with CMD (from - 16.8 ± 2.7 to - 15.8 ± 2.7, p < 0.01). There was a significant inverse correlation between CFR and ∆GLS (r = - 0.82, p < 0.01). Rest GLS and GLS response to dipyridamole stress are markedly impaired among patients with chest pain syndrome, non-obstructive CAD and CMD, reflecting subclinical LV systolic dysfunction and lack of LV contractile reserve due to underlying myocardial ischemia.

Acute myocarditis: prognostic role of speckle tracking echocardiography and comparison with cardiac magnetic resonance features.

To evaluate longitudinal systolic function in patients with myocarditis, its correlation with cardiac magnetic resonance (CMR) features, and its predictive value in functional recovery and arrhythmias onset during follow-up (FU) on optimized medical therapy (OMT). Patients with acute myocarditis, confirmed through CMR criteria, and age- and sex-matched healthy controls were enrolled. Two-dimensional (2D) transthoracic echocardiography, including speckle tracking analysis, was performed at admission and after 6 months of FU. Patients of myocarditis group also underwent 24 h ECG Holter monitoring during FU. 115 patients with myocarditis (mean age 41 ± 17, 70% males) and 70 healthy subjects were enrolled. Global longitudinal strain (GLS) and sub-epicardial strain were markedly lower in the myocarditis group than in controls (mean GLS%: - 14.1 ± 5.1 vs - 23.1 ± 3.6, p < 0.001). A strong positive correlation between total scar burden (TSB) on CMR and baseline LV GLS was found (r = 0.67, p < 0.0001). GLS improved after 6 months of FU in myocarditis on OMT (mean GLS%: - 14.1 ± 5.1 vs - 16.5 ± 4.8, p < 0.01). By bivariate correlation analysis, baseline LVEF, GLS, and TSB were all associated with LVEF at 6 months of FU. Moreover, by multivariable linear regression analysis, these parameters confirmed to be independent predictors of functional recovery at 6 months (LVEF ß 0.38, p < 0.01; GLS ß - 0.35, p < 0.01; total scar burden ß - 0.52, p < 0.0001). Segmental peak systolic strain was significantly different between segments with and without late gadolinium enhancement on CMR (- 13.2 ± 3.1% vs - 18.1 ± 3.5%, p < 0.001). A segmental strain of - 12% identified scar with a sensitivity of 79% and a specificity of 84% (AUC = 0.91; 95% CI 0.73-0.97; p < 0.001). In addition, baseline LV GLS in myocarditis resulted predictive of non-sustained ventricular tachycardias (cut-off value > - 12%; sensitivity84%; specificity74.4%; AUC = 0.75). Parameters of myocardial longitudinal deformation are importantly associated with the presence of a scar on CMR and are predictors of functional outcome and ventricular arrhythmias in patients with acute myocarditis. Their assessment during ultrasound examination should be considered to get more information about the prognosis and risk stratification of this subset of patients.

Echocardiographic assessment of coronary microvascular dysfunction: Basic concepts, technical aspects, and clinical settings.

Coronary flow reserve is the capacity of the coronary circulation to augment the blood flow in response an increase in myocardial metabolic demands and has a powerful prognostic significance in different clinical situations. It might assess with invasive and noninvasive technique. Transthoracic echocardiography Doppler is an emerging diagnostic technique, noninvasive, highly feasible, safe for patient and physician, without radiation, and able to detect macrovascular and microvascular anomalies in the coronary circulation. This review aims to describe the benefit and limits of echocardiographic assessment of coronary flow reserve.

Effects of ranolazine on noninvasive coronary flow reserve in patients with myocardial ischemia but without obstructive coronary artery disease.

INTRODUCTION: Ranolazine reduces the Na-dependent calcium overload via inhibition of the late sodium current, improving diastolic tone and oxygen handling during myocardial ischemia. In patients with angina, evidence of myocardial ischemia, but no obstructive coronary artery disease (CAD), abnormal coronary autoregulation plays a key role. Transthoracic Doppler-derived coronary flow reserve (CFR) is an index of coronary arterial reactivity and decreases in both microvascular dysfunction and coronary artery stenosis. The aim of this study was to assess the effect of ranolazine on CFR in this group of patient. METHODS: Fifty-eight (39M, 19F) patients with angina and evidence of myocardial ischemia, but no obstructive CAD, were enrolled in a double-blind, placebo-controlled trial. Participants were assigned to ranolazine (29) or placebo (29) for 8 weeks (up to 500 mg twice a day). CFR was determined as the ratio of hyperemic, induced by intravenous dypiridamole administration, to baseline diastolic coronary flow velocity. CFR was assessed before and after 8-week therapy. RESULTS: CFR was successfully performed in all patients. There were no significant differences in baseline characteristics and CFR between ranolazine and placebo group. After 8 weeks CFR significantly increased in ranolazine group (2.54 ± 0.44 vs. 1.91 ± 0.31; P = 0.005) but not in placebo group (1.99 ± 0.32 vs. 1.94 ± 0.29; P = ns). No patient dropped out during 8 weeks therapy. Side effects were similar in both groups. CONCLUSIONS: Ranolazine is able to improve CFR in these patients. This is probably due to improvement in abnormal coronary autoregulation, both reducing baseline diastolic coronary flow velocity and increasing hyperemic diastolic coronary flow velocity.

The Incremental Role of Multiorgan Point-of-Care Ultrasounds in the Emergency Setting.

Point-of-care ultrasonography (POCUS) represents a goal-directed ultrasound examination performed by clinicians directly involved in patient healthcare. POCUS has been widely used in emergency departments, where US exams allow physicians to make quick diagnoses and to recognize early life-threatening conditions which require prompt interventions. Although initially meant for the real-time evaluation of cardiovascular and respiratory pathologies, its use has been extended to a wide range of clinical applications, such as screening for deep-vein thrombosis and trauma, abdominal ultrasonography of the right upper quadrant and appendix, and guidance for invasive procedures. Moreover, recently, bedside ultrasounds have been used to evaluate the fluid balance and to guide decongestive therapy in acutely decompensated heart failure. The aim of the present review was to discuss the most common applications of POCUS in the emergency setting.

Potential Role of Global Longitudinal Strain in Cardiac and Oncological Patients Undergoing Cardio-Oncology Rehabilitation (CORE).

Although shown to be effective in improving survival and quality of life in patients with cancer, some treatments are well-known causes of cardiotoxicity, such as anthracyclines, monoclonal antibodies against human epidermal growth factor receptor 2 (HER2) and radiotherapy. To prevent cardiovascular disease (CVD) in patients living with cancer, cardiologists and oncologists promoted the development of cardio-oncology, an interdisciplinary field which aims to further improving life expectancy in these patients. Cardio-oncology rehabilitation (CORE), through correction of risk factors, prescription of drug therapies and structured exercise programs, tries to improve symptoms, quality of life, cardiorespiratory fitness (CRF) and survival in patients with cancer. Different imaging modalities can be used to evaluate the real effectiveness of exercise training on cardiac function. Among these, the global longitudinal strain (GLS) has recently aroused interest, thanks to its high sensitivity and specificity for cardiac dysfunction detection due to advanced ultrasound programs. This review summarizes the evidence on the usefulness of GLS in patients with cancer undergoing cardiac rehabilitation programs.

Secondary prevention and follow-up of patients with ACS and not-at-target LDL: An Italian real-world retro-prospective analysis by the inertia group.

Background: In patients with recent ACS, the latest ESC/EAS guidelines for management of dyslipidaemia recommend intensification of LDL-C-lowering therapy. Objective: Report a real-world picture of lipid-lowering therapy prescribed and cholesterol targets achieved in post-ACS patients before and after a specific educational program. Methods: Retrospective data collection prior to the educational course and prospective data collection after the course of consecutive very high-risk patients with ACS admitted in 2020 in 13 Italian cardiology departments, and with a non-target LDL-C level at discharge. Results: Data from 336 patients were included, 229 in the retrospective phase and 107 in the post-course prospective phase. At discharge, statins were prescribed in 98.1% of patients, alone in 62.3% of patients (65% of which at high doses) and in combination with ezetimibe in 35.8% of cases (52% at high doses). A significant reduction was obtained in total and LDL cholesterol (LDL-C) from discharge to the first control visit. Thirty-five percent of patients achieved a target LDL-C <55 mg/dL according to ESC 2019 guidelines. Fifty percent of patients achieved the <55 mg/dL target for LDL-C after a mean of 120 days from the ACS event. Conclusions: Our analysis, though numerically and methodologically limited, suggests that management of cholesterolaemia and achievement of LDL-C targets are largely suboptimal and need significant improvement to comply with the lipid-lowering guidelines for very high CV risk patients. Earlier high intensity statin combination therapy should be encouraged in patients with high residual risk.

Monday preference in onset of takotsubo cardiomyopathy.

OBJECTIVE: Acute cardiovascular events show definite temporal patterns of occurrence. Takotsubo cardiomyopathy (TTC) has been recently shown to exhibit a seasonal (summer) and circadian (morning) temporal distribution. The aim of this study, based on the database of a multicenter Italian network, was to investigate the possible existence of a weekly pattern of onset of TTC. METHODS: The study included all cases of TTC admitted to the coronary care unit of 8 referral cardiac centers in Italy (five in Southern Italy and three in Northern Italy, respectively), belonging to the Takotsubo Italian Network (January 2002-December 2008). Day of admission was categorized into seven 1-day intervals according by week, and chronobiological analysis was performed by partial Fourier series. RESULTS: The database included 112 patients with TTC (92.9% females). The weekly distribution identified the highest number of cases on Monday and the lowest on Saturday. Chronobiologic analysis yielded a rhythmic pattern with a significant peak on Monday (P = .036). CONCLUSIONS: This study confirms a Monday preference for TTC occurrence on Monday, similar to that reported for acute myocardial infarction. Stress of starting weekly day life activities, could play a triggering role.

Multimodality imaging in COVID-19 patients: A key role from diagnosis to prognosis.

The integrated clinical, laboratory and ultrasound approach is essential for the diagnosis, evaluation and monitoring of the patient's therapy in coronavirus disease 2019 pneumonia. The ideal imaging approach in this context is not yet well defined. Chest X-ray is characterized by low sensitivity in identifying earlier lung changes. The "bedside" pulmonary ultrasound has an undeniable series of advantages in the patient at high infectious risk and can provide incremental data in the respiratory intensive care for the serial control of the individual patient as well as for the home delivery of the stabilized subjects. Pulmonary computed tomography shows high sensitivity but should not be routinely performed in all patients, because in the first 48 h it can be absolutely negative and in the late phase the imaging findings may not change the therapeutic approach. Echocardiography should be limited to patients with hemodynamic instability to assess ventricular function and pulmonary pressures.

Echocardiography in Athletes in Primary Prevention of Sudden Death.

Echocardiography is a noninvasive imaging technique useful to provide clinical data regarding physiological adaptations of athlete's heart. Echocardiographic characteristics may be helpful for the clinicians to identify structural cardiac disease, responsible of sudden death during sport activities. The application of echocardiography in preparticipation screening might be essential: it shows high sensitivity and specificity for identification of structural cardiac disease and it is the first-line imagining technique for primary prevention of SCD in athletes. Moreover, new echocardiographic techniques distinguish extreme sport cardiac remodeling from beginning state of cardiomyopathy, as hypertrophic or dilated cardiomyopathy and arrhythmogenic right ventricle dysplasia. The aim of this paper is to review the scientific literature and the clinical knowledge about athlete's heart and main structural heart disease and to describe the rule of echocardiography in primary prevention of SCD in athletes.

Ivabradine in chronic stable angina: Effects by and beyond heart rate reduction.

Heart rate plays a major role in myocardial ischemia. A high heart rate increases myocardial performance and oxygen demand and reduces diastolic time. Ivabradine reduces heart rate by inhibiting the If current of sinoatrial-node cells. In contrast to beta-blockers, ivabradine has no negative inotropic and lusitropic effect for a comparable heart rate reduction. Consequently, diastolic duration is increased with ivabradine compared to beta-blockers. This has potential consequences on coronary blood flow since compression of the vasculature by the surrounding myocardium during systole impedes flow and coronary blood flow is mainly diastolic. Moreover, ivabradine does not unmask alpha-adrenergic vasoconstriction and, unlike beta-blockers, maintains coronary dilation during exercise. In comparison with beta-blockers, ivabradine increases coronary flow reserve and collateral perfusion promoting the development of coronary collaterals. Ivabradine attenuates myocardial ischemia and its consequences even in the absence of heart rate reduction, possibly through reduced formation of reactive oxygen species. In conclusion, ivabradine differs from other anti-anginal agents by improving coronary blood flow and by additional pleiotropic effects. These properties make ivabradine an effective anti-anginal and anti-ischemic agent for the treatment of patients with coronary artery disease.

Ivabradine and Bisoprolol on Doppler-derived Coronary Flow Velocity Reserve in Patients with Stable Coronary Artery Disease: Beyond the Heart Rate.

INTRODUCTION: Coronary flow velocity reserve (CFVR) is an important prognostic marker in patients with stable coronary artery disease (CAD). Beta-blockers and ivabradine have been shown to improve CFVR in patients with stable CAD, but their effects were never compared. The aim of the current study was to compare the effects of bisoprolol and ivabradine on CFVR in patients with stable CAD. METHODS: Patients in sinus rhythm with stable CAD were enrolled in this prospective, randomized, double-blind trial. Patients had to be in a stable condition for at least 15 days before enrollment, on their usual therapy. Patients who were receiving beta-blockers or ivabradine entered a 2-week washout period from these drugs before randomization. Transthoracic Doppler-derived CFVR was assessed in left anterior descending coronary artery, and was calculated as the ratio of hyperemic to baseline diastolic coronary flow velocity (CFV). Hyperemic CFV was obtained using dipyridamole administration using standard protocols. After CFVR assessment, patients were randomized to ivabradine or bisoprolol and entered an up-titration phase, and CFVR was assessed again 1 month after the end of the up-titration phase. RESULTS: Fifty-nine patients (38 male, 21 female; mean age 69 ± 9 years) were enrolled. Transthoracic Doppler-derived assessment of CFV and CFVR was successfully performed in all patients. Baseline characteristics were similar between the bisoprolol and ivabradine groups. No patient dropped out during the study. At baseline, rest and hyperemic peak CFV as well as CFVR was not significantly different in the ivabradine and bisoprolol groups. After the therapy, resting peak CFV significantly decreased in both the ivabradine and bisoprolol groups, but there was no significant difference between the groups (ivabradine group 20.7 ± 4.6 vs. 22.8 ± 5.2, P < 0.001; bisoprolol group 20.1 ± 4.1 vs. 22.1 ± 4.3, P < 0.001). However, hyperemic peak CFV significantly increased in both groups, but to a greater extent in patients treated with ivabradine (ivabradine: 70.7 ± 9.4 vs. 58.8 ± 9.2, P < 0.001; bisoprolol: 65 ± 8.3 vs. 58.7 ± 8.2, P < 0.001). Accordingly, CFVR significantly increased in both groups (ivabradine 3.52 ± 0.64 vs. 2.67 ± 0.55, P < 0.001; bisoprolol 3.35 ± 0.70 vs. 2.72 ± 0.55, P < 0.001), but it was significantly higher in ivabradine group, despite a similar decrease in heart rate (63 ± 7 vs. 61 ± 6; P not significant). CONCLUSION: Ivabradine improves hyperemic peak CFV and CFVR to a greater extent than bisoprolol in patients with stable CAD, despite a similar decrease in heart rate. These data demonstrate that the benefits from ivabradine therapy go beyond the heart rate. This could be due to a different mechanism such as diastolic perfusion time, isovolumic ventricular relaxation, end-diastolic pressure, and collaterals. FUNDING: Servier.

Effect of weight loss on coronary circulation and adiponectin levels in obese women.

BACKGROUND: Obesity is independently associated with coronary endothelial dysfunction. Adiponectin, a protein whose circulating levels are decreased in obesity, has direct effects on vascular function. The aim of this study was to investigate in obese women the effect of sustained weight loss on coronary circulation and circulating adiponectin levels. METHODS: Coronary flow velocity reserve (CFVR), assessed by transthoracic Doppler echocardiography (TTDE), blood pressure, lipid, glucose and insulin, HOMA scores, CRP-protein (CRP), and adiponectin parameters were investigated in forty obese pre-menopausal women and 40 healthy matched normal weight women at baseline and after sustained weight loss. RESULTS: At baseline, the obese group had significantly higher fasting glucose (P<0.05), insulin concentrations (P<0.01), HOMA scores (P<0.001), C-reactive protein (CRP) levels (P<0.001) and lower plasma adiponectin levels (P<0.001) than the controls. CFVR was significantly lower in obese group than in the normal weight group (P<0.05). After 12 months of a multidisciplinary program of weight reduction, obese women lost at least 10% of their original weight. Fasting glucose (<0.001) and insulin concentrations (P<0.001), HOMA scores (P<0.001), CRP levels (P<0.01) were significant reduced, whereas adiponectin levels (P<0.001) and HDL cholesterol (P<0.05) showed a significant increment. CFVR value significantly improved in obese subjects (P<0.001). There was a significant correlation between changes in CFVR and changes in adiponectin levels (r=0.47, P<0.05). Multivariate analysis showed that adiponectin was the only independent predictor of change in CFVR (r=0.38, P<0.05). CONCLUSIONS: In obese women the weight loss improves coronary circulation and increases adiponectin levels. The improvement in coronary circulation is associated with adiponectin levels.