Efficacy of mitral annular velocity as an alternative marker of left ventricular global longitudinal strain to detect the risk of cancer therapy-related cardiac disorders.

PURPOSE: Left ventricular longitudinal function can be rapidly evaluated by measuring S' and mitral annular plane systolic excursion (MAPSE) using tissue Doppler imaging. Even when the image quality is poor and the left ventricular endocardium is not visible, S' and MAPSE can be measured if the mitral annulus is visible. However, the utility of S' and MAPSE in diagnosing cancer therapy-related cardiac dysfunction (CTRCD) remains unclear. This study aimed to examine the diagnostic performance of S' and MAPSE and determine appropriate cutoff values. METHODS: We retrospectively enrolled 279 breast cancer patients who underwent pre- or postoperative chemotherapy with anthracyclines and trastuzumab from April 2020 to November 2022. We compared echocardiographic data before chemotherapy, 6 months after chemotherapy initiation, and 1 year later. CTRCD was defined as a decrease in left ventricular ejection fraction below 50%, with a decrease of ≥10% from baseline or a relative decrease in left ventricular global longitudinal strain (LVGLS) of ≥15%. RESULTS: A total of 256 participants were included in this study, with a mean age of 50.2 ± 11 years. Fifty-six individuals (22%) developed CTRCD within 1 year after starting chemotherapy. The cutoff value for septal S' was 6.85 cm/s (AUC = .81, p < .001; sensitivity 74%; specificity 73%), and for MAPSE was 11.7 mm (AUC = .65, p = .02; sensitivity 79%; specificity 45%). None of the cases with septal S' exceeding 6.85 cm/s had an LVGLS of ≤15%. CONCLUSIONS: Septal S' is a useful indicator for diagnosing CTRCD. HIGHLIGHTS: Septal S' decreased at the same time or earlier than the decrease in LVGLS. The septal S' demonstrated higher diagnostic ability for CTRCD compared to LVGLS.

External Validation of the HELT-E2S2 Score in Japanese Patients With Nonvalvular Atrial Fibrillation　- A Pooled Analysis of the RAFFINE and SAKURA Registries.

BACKGROUND: The HELT-E2S2score, which assigns 1 point to Hypertension, Elderly aged 75-84 years, Low body mass index <18.5 kg/m2, and Type of atrial fibrillation (AF: persistent/permanent), and 2 points to Extreme Elderly aged ≥85 years and previous Stroke, has been proposed as a new risk stratification for strokes in Japanese AF patients, but has not yet undergone external validation.Methods and Results: We evaluated the prognostic performance of the HELT-E2S2score for stroke risk stratification using 2 large-scale registries in Japanese AF patients (n=7,020). During 23,241 person-years of follow-up (mean follow-up 1,208±450 days), 287 ischemic stroke events occurred. The C-statistic using the HELT-E2S2score was 0.661 (95% confidence interval [CI], 0.629-0.692), which was numerically higher than with the CHADS2score (0.644, 95% CI 0.613-0.675; P=0.15 vs. HELT-E2S2) or CHA2DS2-VASc score (0.650, 95% CI, 0.619-0.680; P=0.37 vs. HELT-E2S2). In the SAKURA AF Registry, the C-statistic of the HELT-E2S2score was consistently higher than the CHADS2and CHA2DS2-VASc scores across all 3 types of facilities comprising university hospitals, general hospitals, and clinics. However, in the RAFFINE Study, its superiority was only observed in general hospitals. CONCLUSIONS: The HELT-E2S2score demonstrated potential value for risk stratification, particularly in a super-aged society such as Japan. However, its superiority over the CHADS2or CHA2DS2-VASc scores may vary across different hospital settings.

Associations among preoperative transthoracic echocardiography variables and cerebral near-infrared spectroscopy values at baseline before anesthesia in patients undergoing cardiac surgery: a retrospective observational study.

Cerebral tissue oximetry with near-infrared spectroscopy (NIRS) is used to monitor cerebral oxygenation during cardiac surgery. To date, reduced baseline cerebral NIRS values have been attributed to reduced cerebral blood flow primarily based on a significant positive correlation between left ventricular ejection fraction (LVEF) and baseline rSO2 measured with the INVOS 5100C oximeter. Reportedly, however, rSO2, but not StO2 measured with the FORESIGHT Elite oximeter, correlated with LVEF. We, thus, investigated associations among baseline NIRS values measured with three different oximeters before anesthesia for cardiac surgery and preoperative transthoracic echocardiography (TTE) variables, including LVEF, to examine whether there are inter-device differences in associations among baseline NIRS values and TTE variables. Using Spearman's correlation coefficient, we retrospectively investigated associations among 15 preoperative TTE variables, including LVEF, and baseline NIRS values, including rSO2, StO2, and TOI with the NIRO-200NX oximeter in 1346, 515, and 301 patients, respectively. Only rSO2 (p < 0.00001), but not TOI or StO2 (p > 0.05), positively correlated with LVEF. On the other hand, baseline rSO2, TOI, and StO2 consistently, negatively correlated with the left atrial diameter index (LADI), early diastolic transmitral flow velocity (E), E-to-early diastolic mitral annular velocity ratio (E/e'), estimated right ventricular systolic pressure (eRVP), and inferior vena cava diameter index (IVCDI) (p < 0.0005 to p < 0.00001). Because all of these five TTE variables could be positively associated with right as well as left ventricular filling pressure, our results indicated that reduced baseline NIRS values were consistently associated not with reduced LVEF but with TTE findings indicative of elevated biventricular filling pressure. Our data suggest that regional venous congestion greatly contributes to reduced baseline NIRS values in patients undergoing cardiac surgery.

Rationale and Design of the Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT): A Pilot Study.

BACKGROUND: Cancer therapeutics-related cardiac dysfunction (CTRCD) is a well-recognised complication of cancer treatment. Treatment of CTRCD involves cardioprotective therapy (CPT) which can lead to a recovery of CTRCD with normalisation of the left ventricular ejection fraction (LVEF). As a result, there are potentially millions of cancer survivors with recovered CTRCD on CPT. Cardioprotective therapy can be associated with an undesirable long-term pill burden, financial costs, and side effects. Cancer survivorship is anticipated to increase significantly by the end of this decade. To date, there is no evidence of the safety of stopping CPT in this setting. This study seeks to evaluate the hypothesis that ceasing cardioprotective medication is a feasible and safe option without significant impact on LVEF in low-risk patients who have recovered from CTRCD. METHODS AND ANALYSIS: We will perform a multicentre prospective open-label randomised controlled trial with blinded endpoint (PROBE) of supervised CPT cessation compared to continuing CPT (control). The primary study end point is the change in LVEF by cardiac magnetic resonance imaging at 6 months of enrolment between the two groups. Secondary end points include changes in quality-of-life questionnaires, other cardiac imaging parameters, and recurrence of heart failure. CONCLUSION: Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT) is one of the first studies currently underway to evaluate the safety of ceasing CPT in recovered CTRCD. The results will inform clinical practice in this evidence-free zone.

Involvement of kallikrein-PAR2-proinflammatory pathway in severe trastuzumab-induced cardiotoxicity.

Trastuzumab-induced cardiotoxicity interferes with continued treatment in approximately 10% of patients with ErbB2-positive breast cancer, but its mechanism has not been fully elucidated. In this study, we recruited trastuzumab-treated patients with ≥30% reduction in left ventricular ejection fraction (SP) and noncardiotoxic patients (NP). From each of these patients, we established three cases of induced pluripotent stem cell-derived cardiomyocytes (pt-iPSC-CMs). Reduced contraction and relaxation velocities following trastuzumab treatment were more evident in SP pt-iPSC-CMs than NP pt-iPSC-CMs, indicating the cardiotoxicity phenotype could be replicated. Differences in ATP production, reactive oxygen species, and autophagy activity were observed between the two groups. Analysis of transcripts revealed enhanced kallikrein5 expression and pro-inflammatory signaling pathways, such as interleukin-1ß, in SP pt-iPSC-CMs after trastuzumab treatment. The kallilkrein5-protease-activated receptor 2 (PAR2)-MAPK signaling pathway was more activated in SP pt-iPSC-CMs, and treatment with a PAR2-antagonist suppressed interleukin-1ß expression. Our data indicate enhanced pro-inflammatory responses through kallikrein5-PAR2 signaling and vulnerability to external stresses appear to be the cause of trastuzumab-induced cardiotoxicity in SP.

Comparison of primary and secondary stroke prevention in patients with nonvalvular atrial fibrillation: Results from the RAFFINE registry.

OBJECTIVES: Clinical outcome data of primary and secondary prevention in patients with nonvalvular atrial fibrillation (NVAF) after the introduction of direct oral anticoagulant (DOAC) therapy are limited. MATERIALS AND METHODS: A subgroup analysis of the RAFFINE registry, an observational, multicenter, prospective registry of Japanese patients with AF, was performed. Incidence rates of stroke or systemic embolism, all-cause death, major bleeding, and intracranial hemorrhage were compared between patients with and without a history of stroke or transient ischemic attack (TIA). RESULTS: Of 3,706 NVAF patients at baseline, 557 (15.0%) had a history of ischemic stroke or TIA (secondary prevention group), and 3,149 (85.0%) had no history of ischemic stroke or TIA (primary prevention group). The proportion of patients receiving oral anticoagulants was 87.2% (42.5% warfarin, 44.7% DOACs). The secondary prevention group had higher rates of stroke or systemic embolism (2.6% vs 1.0%/year, p<0.001), all-cause death (3.6% vs 2.4%/year, p<0.01), and major bleeding (2.0% vs 1.3%/year, p<0.01), and similar rates of intracranial hemorrhage (0.6% vs 0.5%/year, p=0.66) compared with the primary prevention group. A Cox proportional hazards model showed that a history of ischemic stroke or TIA was independently associated with an increased risk of stroke or systemic embolism (adjusted hazard ratio, 2.22; 95% confidence interval, 1.57 - 3.15; p<0.001). CONCLUSIONS: In a contemporary cohort of NVAF patients, a history of ischemic stroke or TIA was still an independent predictor of stroke or systemic embolism, despite advances in anticoagulation therapy.

[Tyrosine kinase inhibitor-associated cardiovascular adverse events in chronic myeloid leukemia].

BCR-ABL tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML). Currently, five BCR-ABL TKIs are approved for use in patients with CML, but the long-term use of these TKIs is associated with various cardiovascular events. Typical cardiovascular adverse events include pulmonary hypertension caused by dasatinib and arterial occlusive diseases caused by nilotinib and ponatinib. Although mechanisms of cardiovascular adverse events of BCR-ABL TKIs in the treatment of CML have not been clarified, differences in their inhibitory activities on off-target kinases, including those involved in vascular function, may be related to individual safety profiles. Arterial occlusive diseases are common in patients with a history of cardiovascular disease and risk of atherosclerosis. Arterial occlusive diseases, such as ischemic heart disease, ischemic cerebral disease, and peripheral arterial occlusive disease, worsen the prognosis and quality of life of patients with CML. Therefore, appropriate management strategies are required. This paper outlines cardiovascular adverse events associated with TKI treatment, including arterial obstructive diseases, pulmonary arterial hypertension, and QT interval prolongation.

Comparison Between Healthcare-Associated and Community-Acquired Infective Endocarditis at Tertiary Care Hospitals in Japan.

BACKGROUND: Healthcare-associated infective endocarditis (HAIE) has become increasingly recognized worldwide because the underlying patient conditions are completely different from those of community-acquired infective endocarditis (CIE). However, data on HAIE in the Japanese population is lacking. We sought to clarify the patient characteristics and prognosis of HAIE in a Japanese population.Methods and Results:A retrospective study was conducted in 158 patients who were diagnosed with infective endocarditis, 53 of whom (33.5%) were classified as HAIE. Compared with patients with CIE, those with HAIE were older (median age 72 vs. 61 years; P=0.0002) and received surgical treatment less frequently (41.5% vs. 62.9%; P=0.01). Regarding causative microorganisms, staphylococci,including methicillin-resistant pathogens, were more common in patients with HAIE (32.1% vs. 14.3%; P=0.01). Patients with HAIE had higher in-hospital mortality (32.1% vs. 4.8%; P<0.0001) and Kaplan-Meier analysis showed worse prognosis for patients with HAIE than CIE (P<0.0001, log-rank test). On multivariate Cox analysis, HAIE (hazard ratio 3.26; 95% confidence interval 1.49-7.14), age ≥60 years, surgical treatment, stroke, and heart failure were independently associated with mortality. CONCLUSIONS: HAIE has different clinical characteristics and causative microorganisms, as well as worse prognosis, than CIE. Preventive strategies, and the prompt and appropriate identification of HAIE may improve the outcome of infective endocarditis.

Echocardiography and Cardio-Oncology.

Owing to the ongoing increase in cancer survivors because of the remarkable and continuous progress in cancer management, a paradigm shift is occurring from cancer as a 'terminal illness' to a 'chronic condition' with cardiovascular risks. This also affects cardiology practice with increased cardiovascular morbidity and mortality rates among patients with cancer due to direct and/or indirect side effects of anticancer treatment. Thus, cardio-oncology has emerged as a new cardiology subspecialty, which focusses on risk stratification, prevention, diagnosis, treatment, and follow-up of cardiovascular disease related to cancer treatment. This review summarises echocardiographic evaluation of cardiac dysfunction and heart failure as they are the most concerning cardiovascular complications of cancer therapy and worsen its morbidity and mortality. This review covers cardiac function assessment and proposed cut-off values before/during/after cancer chemotherapy. The goal of this review is to aid clinicians to manage the patients with cancer sufficiently by connecting the existing knowledge in clinical cardiology with novel information from current advances in cardio-oncology.

Significance of Coronary Artery Disease and Left Ventricular Afterload in Unoperated Asymptomatic Aortic Stenosis.

BACKGROUND: Because the covariates of cardiovascular events in unoperated patients with asymptomatic aortic stenosis (AS) have not been adequately evaluated, we aimed to identify them. METHODS AND RESULTS: A total of 230 patients with asymptomatic severe AS were retrospectively enrolled. The patients were divided into 2 groups based on aortic valve replacement (AVR) after enrollment: a non-AVR group (n=112), and an AVR group (n=118). The primary clinical endpoint was cardiovascular events, which were defined as cardiovascular death or hospitalization. Coronary artery disease [hazard ratio (HR): 3.62, 95% confidence interval (CI): 1.585-8.245, P<0.01] and high valvulo-arterial impedance (HR: 3.08, 95% CI: 1.261-7.532, P<0.05) were identified as independent covariates of cardiovascular events in the non-AVR group. The relative risk of cardiovascular events rose with an increase in the number of risk factors (P<0.0001). CONCLUSIONS: In unoperated patients with asymptomatic AS, the presence of coronary artery disease and increased global left ventricular afterload may be associated with a poor prognosis.

Coronary microvascular function is independently associated with left ventricular filling pressure in patients with type 2 diabetes mellitus.

BACKGROUND: Left ventricular (LV) diastolic dysfunction is known as an early marker of myocardial alterations in patients with diabetes. Because microvascular disease has been regarded as an important cause of heart failure or diastolic dysfunction in diabetic patients, we tested the hypothesis that coronary flow reserve (CFR), which reflects coronary microvascular function, is associated with LV diastolic dysfunction in patients with type 2 diabetes. METHODS: We studied asymptomatic patients with type 2 diabetes but without overt heart failure. Transthoracic Doppler echocardiography was performed that included pulsed tissue Doppler of the mitral annulus and CFR of the left anterior descending artery (induced by adenosine 0.14 mg/kg/min). The ratio of mitral velocity to early diastolic velocity of the mitral annulus (E/e') was used as a surrogate marker of diastolic function. We also evaluated renal function, lipid profile, parameters of glycemic control and other clinical characteristics to determine their association with E/e'. Patients with LV ejection fraction <50%, atrial fibrillation, valvular disease, regional wall motion abnormality, renal failure (serum creatinine >2.0 mg/dl) or type 1 diabetes were excluded. Patients with a CFR <2.0 were also excluded based on the suspicion of significant coronary artery stenosis. RESULTS: We included 67 asymptomatic patients with type 2 diabetes and 14 non-diabetic controls in the final study population. In univariate analysis, age, presence of hypertension, LV mass index, estimated glomerular filtration rate and CFR were significantly associated with E/e'. Multivariate analysis indicated that both LV mass index and CFR were independently associated with E/e'. In contrast, there were no significant associations between parameters of glycemic control and E/e'. CONCLUSIONS: CFR was associated with LV filling pressure in patients with type 2 diabetes. This result suggests a possible link between coronary microvascular disease and LV diastolic function in these subjects.

Comparison of 2-year outcomes between zotarolimus-eluting and everolimus-eluting new-generation cobalt-chromium alloy stents in real-world diabetic patients.

BACKGROUND: To date, it remains unknown whether different types of new-generation drug-eluting stents have a differential impact on long-term outcomes in diabetic patients. METHODS AND RESULTS: In this historical cohort study (two Italian centers), we analyzed 400 diabetic patients with 553 coronary lesions treated with new-generation CoCr zotarolimus-eluting stents (R-ZES: 136 patients, 196 lesions) or everolimus-eluting stents (EES: 264 patients, 357 lesions) between October 2006 and August 2012. Primary endpoint was the occurrence of major adverse cardiac events (MACE) over a 2-year follow-up period. MACE was defined as all-cause mortality, any myocardial infarction (MI) and/or target lesion revascularization (TLR). Multivessel revascularization, intervention for restenotic lesion and use of intravascular ultrasound were significantly higher in the R-ZES group, whereas small stent (≤2.5 mm) deployment was significantly higher in the EES group. At 2-year follow-up, there was no significant difference in occurrence of MACE (R-ZES vs EES: 22.8% vs 18.9%, P = 0.39). Similarly, no significant differences were observed in the composite endpoint of all-cause mortality/MI (10.0% vs 10.3%, P = 0.86) or TLR (12.4% vs 7.4%, P = 0.11). Adjustment for confounders and baseline propensity-score matching did not alter the aforementioned associations. CONCLUSION: After 2 years of follow up similar outcomes (MACE, all-cause mortality/MI, TLR) were observed in real-world diabetic patients, including those with complex lesions and patient characteristics, treated with R-ZES and EES.

Assessment of elevation of and rapid change in left ventricular filling pressure using a novel global strain imaging diastolic index.

BACKGROUND: The aim of this study was to determine whether global strain imaging diastolic index (SIDI) obtained using 2-D speckle tracking imaging (2DSI) could predict elevation in and rapid change of LV filling pressure. METHODS AND RESULTS: Patients (n=126) underwent echocardiography and 2DSI during simultaneous cardiac catheterization. There were 60 patients in whom the same measurements were repeated 5min after i.v. glyceryl trinitrate. LV pre-atrial contraction pressure (pre-A) was measured as a surrogate of LV filling pressure. SIDI was defined as the change of LV longitudinal strain measured using 2DSI during the first one-third of diastole. Then, longitudinal global SIDI (L-global SIDI) was calculated as the mean SIDI of 18 LV segments. Mitral inflow and tissue Doppler imaging were also assessed. Among 126 patients, 93 patients had LV pre-A ≥15mmHg. L-global SIDI had a better correlation with LV pre-A (P<0.001, r=-0.56) than E/e' (P<0.01, r=0.35). On receiver operating characteristic curve analysis, L-global SIDI <0.48 was the optimum cut-off to predict LV pre-A ≥15mmHg (sensitivity, 82%; specificity, 68%). In addition, the ratio of L-global SIDI (after nitrate/before nitrate) was correlated with the ratio of LV pre-A (after nitrate/before nitrate; P=0.02, r=-0.34). CONCLUSIONS: A novel L-global SIDI derived from 2DSI may reflect elevated LV filling pressure and its rapid change better than conventional diastolic parameters.

Early hemodynamic performance of the trifecta bioprosthetic valve in patients with aortic valve disease.

BACKGROUND: The Trifecta valve (St Jude Medical) is a novel supra-annular aortic bioprosthesis designed to improve hemodynamic performance. We hypothesized that the Trifecta may offer better hemodynamic performance in Japanese patients, in whom the annulus is smaller, compared with Western populations. We compared the early results of hemodynamic performance between the Trifecta and the Magna (Edwards Lifescience) valves at our institution. METHODS AND RESULTS: The Trifecta was implanted in 33 patients and the Magna was implanted in 41 patients who had aortic valve disease. Postoperative echocardiography was performed just before discharge, and the mean pressure gradient (MPG), effective orifice area (EOA) index and energy loss coefficient (ELCo) index were compared between the 2 groups. The average prosthesis size was similar between the 2 groups (21.1 vs. 21.3mm). The Trifecta group had a significantly lower MPG (P=0.001) and larger EOA index and ELCo index than the Magna group (P<0.001 for both). On multivariate linear regression analysis, use of the Trifecta was the strongest independent determinant of postoperative MPG, EOA and ELCo index. CONCLUSIONS: The Trifecta valve provides excellent early postoperative hemodynamic performance in Japanese patients. Patients with a small annulus size relative to body size may benefit more from the Trifecta in terms of postoperative hemodynamic performance.

Influencing factors on cardiac structure and function beyond glycemic control in patients with type 2 diabetes mellitus.

BACKGROUND: We hypothesized that clinical factors other than glycemic control may influence abnormal cardiac function in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the independent factors for abnormal cardiac function among clinical factors in T2DM. METHODS: We studied 148 asymptomatic patients with T2DM without overt heart disease. Echocardiographic findings were compared between diabetic patients and 68 age-matched healthy subjects. Early (E) and late (A) diastolic mitral flow velocity and early diastolic mitral annular velocity (e') were measured for assessing left ventricular (LV) diastolic function. We evaluated insulin resistance, non-esterified fatty acid, high-sensitive CRP, estimated glomerular filtration rate, waist/hip ratio, abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and other clinical characteristics in addition to glycemic control. VAT and SAT were quantified by computed tomography. RESULTS: In T2DM, E/A and e' were significantly lower, and E/e', left atrial volume and LV mass were significantly greater than in control subjects. In multivariate liner regression analysis, VAT was an independent determinant of left atrial volume (ß =0.203, p=0.011), E/A (ß =-0.208, p=0.002), e' (ß =-0.354, p<0.001) and E/e' (ß=0.220, p=0.003). Age was also an independent determinant, whereas fasting plasma glucose and hemoglobin A1c levels were not. In addition to systolic blood pressure, waist-hip ratio (ß=0.173, p=0.024) and VAT/SAT ratio (ß=0.162, p=0.049) were independent determinants of LV mass. CONCLUSION: Excessive visceral fat accompanied by adipocyte dysfunction may play a greater role than glycemic control in the development of diastolic dysfunction and LV hypertrophy in T2DM.

Prognostic value of coronary flow reserve assessed by transthoracic Doppler echocardiography on long-term outcome in asymptomatic patients with type 2 diabetes without overt coronary artery disease.

BACKGROUND: Cardiovascular risk stratification of asymptomatic diabetic patients is important and remains a difficult clinical problem. Our aim was to test the hypothesis that coronary flow reserve (CFR) assessed by noninvasive transthoracic Doppler echocardiography predicts prognosis in those patients. METHODS: From February 2002 to January 2005, we evaluated 135 consecutive asymptomatic patients (74 male; mean age, 63 ± 9 years) with type 2 diabetes without a history of coronary artery disease. Adenosine triphosphate (0.14 mg/kg/min) stress Doppler echocardiography was performed to evaluate CFR of the left anterior descending artery. Patients with a CFR < 2.0 were also excluded based on the suspicion of significant coronary artery stenosis in the left anterior descending artery. RESULTS: There were 111 patients (60 male; mean age, 64 ± 9 years) enrolled. During a median follow-up of 79 months, 20 events (5 deaths, 7 acute coronary syndromes, 8 coronary revascularizations) occurred. The optimal cut-off value of CFR to predict events was 2.5 (area under the receiver-operating characteristic curve = 0.65). Multivariate analysis showed that the independent prognostic indicators were male gender (p < 0.05) and a CFR < 2.5 (p < 0.01). Kaplan-Mayer analysis revealed that the event rate was significantly higher (log-lank, p < 0.01) in patients with CFR < 2.5 than in those with CFR ≥ 2.5. CONCLUSIONS: CFR obtained by transthoracic Doppler echocardiography provides independent prognostic information in asymptomatic patients with type 2 diabetes without overt coronary artery disease. Patients with CFR < 2.5 had a worse long-term outcome.

Clinical factors associated with classical symptoms of aortic valve stenosis.

BACKGROUND AND AIM OF THE STUDY: The recognition of clinical symptoms is critical to a therapeutic strategy for aortic valve stenosis (AS). It was hypothesized that AS symptoms might have multiple causes; hence, a study was conducted to investigate the factors that separately influence the classic symptoms of dyspnea, angina and syncope in AS. METHODS: The medical records of 170 consecutive patients with AS (> or = moderate grade) were reviewed. A multivariate logistic regression analysis was used to evaluate the hemodynamic and clinical factors that separately influence the development of three clinical symptoms: dyspnea (defined as NYHA class > or = 2), angina, and syncope. RESULTS: The most common symptom was dyspnea (47.1%), followed by angina (12.4%) and syncope (4.7%). The factors associated with dyspnea were a higher e' ratio (p = 0.04) and peak aortic valve velocity (p = 0.01). Only the severity of AS was associated with syncope. The presence of hypertension was associated with angina (p = 0.04). Moreover, coronary angiography was performed in 59 patients before aortic valve replacement and revealed coronary stenosis (> 50% diameter stenosis) in 11/16 patients (69%) that had angina. The presence of coronary stenosis was significantly associated with angina (p = 0.02). The development of dyspnea, angina or syncope was influenced by different factors in AS. CONCLUSION: Dyspnea and syncope were mainly associated with AS severity, and diastolic dysfunction also influenced dyspnea. In contrast, angina was mainly related to the presence of coronary stenosis rather than to AS severity. These factors should be considered when, selecting a therapeutic strategy for AS patients in the modern era.

Prediction of coronary artery stenosis at rest in patients with normal left ventricular wall motion. Segmental analyses using strain imaging diastolic index.

Noninvasive detection of coronary artery stenosis usually requires a stress test in patients without left ventricular (LV) regional wall motion abnormalities (RWMA). In contrast, abnormal regional LV relaxation caused by ischemia may persist beyond recovery from transient ischemia. The aim of the present study was to determine whether segmental analysis of abnormal regional LV relaxation using the strain imaging diastolic index (SI-DI) at rest could predict coronary artery stenosis in the three major vessels in patients without LV dysfunction or RWMA. We performed 2D speckle tracking echocardiography and coronary angiography in 85 patients without RWMA with suspected coronary artery disease. Patients with LV dysfunction or acute coronary syndrome were excluded. Echocardiographic images of the LV were obtained in the apical 2-, 3-, and 4-chamber views and divided into 6 segments. In each segment, SI-DI derived from transverse strain imaging was determined. Forty-eight patients had significant coronary artery stenosis (≥ 70%). The optimal cutoff values of SI-DI were 60.5% in the mid anteroseptal segment for detecting left anterior descending artery stenosis (sensitivity, 83.3%; specificity, 81.1%), 60.5% in the basal anterolateral segment for detecting left circumflex artery stenosis (sensitivity, 80.9%; specificity, 90.3%), and 61.5% in the basal inferior segment for detecting right coronary artery stenosis (sensitivity, 74.1%; specificity, 77.8%). A segmental analysis of SI-DI at rest predicted coronary artery stenosis in the three major vessels in patients without RWMA. This noninvasive method may be useful for detecting coronary artery stenosis without a stress test.

Endothelial function measured by peripheral arterial tonometry in patients with chronic myeloid leukemia on tyrosine kinase inhibitor therapy: a pilot study.

BACKGROUND: Arterial occlusive events are an emerging problem in patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor (TKI) therapy. Endothelial cell damage is thought to play an important role in the development of vascular events. Measurement of the peripheral vasodilator response by peripheral arterial tonometry (PAT) has reportedly been useful in the non-invasive assessment of endothelial dysfunction. To date, no studies have assessed endothelial function using PAT in patients with CML receiving TKIs. METHOD: We measured the reactive hyperemia index (RHI) using PAT in young patients with CML (men aged ≤ 55 years and women aged ≤ 65 years) receiving TKIs. RESULTS: Thirty patients with CML were examined (mean age, 43.5 ± 9.8 years; men, 57%). The median RHI was 1.81. Among these patients, 16.7% and 83.3% were taking imatinib and second- or third-generation TKIs, respectively. There were no differences in the baseline characteristics between the low RHI (< 1.67, n = 10), borderline RHI (≥ 1.67 and < 2.10, n = 14), and normal RHI (≥ 2.10, n = 6) groups. Serum uric acid (UA) levels and the RHI were significantly negatively correlated (r = -0.40, p = 0.029). CONCLUSION: One-third of young patients with CML receiving TKI therapy were classified as having a low RHI. The RHI was negatively correlated with serum UA level. Larger prospective studies are necessary to examine whether the RHI predicts cardiovascular events in such patients.

Predicting new-onset heart failure hospitalization of patients with atrial fibrillation: development and external validations of a risk score.

AIM: Atrial fibrillation (AF) is a well-known risk factor for heart failure (HF). We sought to develop and externally validate a risk model for new-onset HF admission in patients with AF and those without a history of HF. METHODS AND RESULTS: Using two multicentre, prospective, observational AF registries, RAFFINE (2857 patients, derivation cohort) and SAKURA (2516 patients without a history of HF, validation cohort), we developed a risk model by selecting variables with regularized regression and weighing coefficients by Cox regression with the derivation cohort. External validity testing was used for the validation cohort. Overall, 148 (5.2%) and 104 (4.1%) patients in the derivation and validation cohorts, respectively, developed HF during median follow-ups of 1396 (interquartile range [IQR]: 1078-1820) and 1168 (IQR: 844-1309) days, respectively. In the derivation cohort, age, haemoglobin, serum creatinine, and log-transformed brain natriuretic peptide were identified as potential risk factors for HF development. The risk model showed good discrimination and calibration in both derivations (area under the curve [AUC]: 0.80 [95% confidence interval (CI) 0.76-0.84]; Hosmer-Lemeshow, P = 0.257) and validation cohorts (AUC: 0.78 [95%CI 0.74-0.83]; Hosmer-Lemeshow, P = 0.475). CONCLUSION: The novel risk model with four readily available clinical characteristics and biomarkers performed well in predicting new-onset HF admission in patients with AF.