TWARMI pilot trial: The value and optimal criteria of microvolt T-wave alternans in the diagnosis of reversible myocardial ischemia in patients without structural cardiac disease.

AIMS: Microvolt T-wave alternans (MTWA) testing is a beat-to-beat fluctuation in the amplitude of T wave. We investigated whether: (a) MTWA can be new non-invasive tool for detection of reversible ischemia in patients with suspected CAD without structural heart disease, (b) MTWA can detect ischemia earlier and with greater test accuracy compared with exercise ECG ST-segment testing, and (c) threshold value of MTWA and heart rate at which the alternans is estimated can be different compared to standard values. METHODS: A total of 101 patients with suspected stable coronary disease, but without structural heart disease, were included. Echocardiography, exercise ECG test, MTWA with classical and modified threshold alternans values, and coronary angiography were performed. RESULTS: About 33.3% patients had a false-positive result on exercise ECG test. The sensitivity of exercise ECG ST-segment test in the detection of coronary artery disease was 97.8%, and the specificity was 42.5% (DOR 33.89). In a group of angiographically positive patients, standard MTWA accurately identified 60% of patients, while 40% had a false-negative result. About 91.8% patients with negative angiography result were accurately identified with 8.2% false positives. The sensitivity of MTWA was 59.61% and specificity 91.83%. Best ratio of sensitivity and specificity (86.53% and 95.91%, DOR 151.06) had modified criteria for positive MTWA (MTWA >1.5 µV at heart rate 115-125/min). CONCLUSIONS: This study showed that MTWA can be the new non-invasive tool for the detection of reversible ischemia in patients with suspected CAD without structural heart disease. Also, MTWA can detect ischemia earlier and with greater accuracy compared with exercise ECG testing.

Association between plasma ceramides and inducible myocardial ischemia in patients with established or suspected coronary artery disease undergoing myocardial perfusion scintigraphy.

BACKGROUND: Recent studies have suggested that specific plasma ceramides are independently associated with major adverse cardiovascular events in patients with coronary artery disease (CAD), but it is currently unknown whether plasma ceramide levels are associated with stress-induced reversible myocardial ischemia. METHODS: We measured six previously identified high-risk plasma ceramide molecules [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1)] in 167 consecutive patients with established or suspected CAD who underwent either exercise or dypiridamole myocardial perfusion scintigraphy (MPS) for various clinical indications. Plasma ceramide levels were measured by a targeted liquid chromatography-tandem mass spectrometry assay both at baseline and after MPS. RESULTS: Seventy-eight patients had inducible myocardial ischemia on stress MPS. Women had significantly higher circulating levels of basal and post-stress Cer(d18:1/16:0) and Cer(d18:1/18:0) compared to men, whereas all other plasma ceramides did not differ between the sexes. Of the six measured plasma ceramides, basal Cer(d18:1/24:1) showed the strongest association with the presence of stress-induced myocardial perfusion defects in univariate analysis (unadjusted-odds ratio 1.48 per 1-SD increment, 95% confidence interval 1.08-2.04). Notably, after adjustment for age, sex, smoking, dyslipidemia, hypertension, diabetes, prior history of CAD, left ventricular ejection fraction, and type of stress testing (exercise vs. dypiridamole), all measured ceramides, except for plasma Cer(d18:1/24:0), were independently associated with the presence of inducible myocardial ischemia. CONCLUSIONS: Distinct plasma ceramides are positive and independent predictors of stress-induced myocardial perfusion defects in patients with established or suspected CAD referred for clinically indicated MPS. Further research is needed to examine whether distinct plasma ceramides could be a useful therapeutic target for treatment and management of CAD.

Percutaneous Left Atrial Appendage Closure with WATCHMAN™ device: peri-procedural and mid-term outcomes from the TRAPS Registry.

PURPOSE: The WATCHMAN device for Left Atrial Appendage Occlusion (LAAO) has proven to be an effective alternative to oral anticoagulation (OAC) in patients with atrial fibrillation (AF), and has now been adopted in clinical practice. In the present study, we analyzed the safety and efficacy profile of the LAAO procedure at mid-term follow-up. METHODS: The TRAPS Registry is an observational, multicenter registry involving four Italian centers. Consecutive patients who had undergone LAAO with WATCHMAN device were enrolled. Clinical, demographic, and procedural data were collected at the time of implantation, and follow-up data were collected to assess the clinical outcome. RESULTS: A total of 151 patients were included in the Registry from May 2012 to October 2015. Implantation of the device was successful in 150/151 patients, with no or minimal (< 5 mm) leakage as assessed by peri-procedural transesophageal echo. In the remaining patient, early device embolization was reported, with no sequelae. Overall, intra-procedural events were reported in 5 (3.3%) patients. During a median follow-up of 16 months (25th and 75th percentile, 10-25), 5 patients died of any cause. The annual rate of all-cause stroke was 2.2% (95% CI, 0.7-5.1), the rate of transient ischemic attack was 1.3% (95% CI, 0.3-3.8), and that of major bleeding 0.4% (95% CI, 0.01-2.4). CONCLUSIONS: LAAO for stroke prevention was safely and effectively achieved by implantation of the WATCHMAN device in patients with non-valvular AF. Moreover, regardless of the risk profile of the population, we observed low rates of death and thromboembolic and bleeding events over a median follow-up of 16 months. These findings were obtained in an unselected group of consecutive patients who were variably eligible for chronic OAC therapy.

Early impairment in left ventricular longitudinal systolic function is associated with an increased risk of incident atrial fibrillation in patients with type 2 diabetes.

AIMS: It is known that type 2 diabetic patients are at high risk of atrial fibrillation (AF). However, the early echocardiographic determinants of AF vulnerability in this patient population remain poorly known. METHODS: We followed-up for 2years a sample of 180 consecutive outpatients with type 2 diabetes, who were free from AF and ischemic heart disease at baseline. All patients underwent a baseline echocardiographic-Doppler evaluation with tissue Doppler and 2-D strain analysis. Standard electrocardiograms were performed twice per year, and a diagnosis of incident AF was confirmed in affected patients by a single cardiologist. RESULTS: Over the 2-year follow-up period, 14 (7.8%) patients developed incident AF. In univariate analyses, echocardiographic predictors of new-onset AF were greater indexed cardiac mass, larger indexed left atrial volume (LAVI), lower global longitudinal strain (LSSYS), lower global diastolic strain rate during early phase of diastole (SRE), lower global diastolic strain rate during late phase of diastole (SRL), and higher E/SRE ratio. Multivariate logistic regression analysis showed that lower LSSYS remained the only significant predictor of new-onset AF (adjusted-odds ratio 1.63, 95%CI 1.17-2.27; p<0.005) after adjustment for age, sex, diabetes duration, indexed cardiac mass and LAVI. Results were unchanged even after adjustment for body mass index, hypertension and glycemic control. CONCLUSIONS: This is the first prospective study to show that early LSSYS impairment independently predicts the risk of new-onset AF in type 2 diabetic patients with preserved ejection fraction and without ischemic heart disease. Future larger prospective studies are needed to confirm these findings.

Relationship between increased left atrial volume and microvascular complications in patients with type 2 diabetes.

AIMS: We assessed whether left atrial volume index (LAVI) was associated with the presence of microvascular complications in patients with type 2 diabetes, and whether this association was independent of hemodynamic and non-hemodynamic factors. METHODS: We studied 157 consecutive outpatients with type 2 diabetes with no previous history of ischemic heart disease, chronic heart failure and valvular diseases. A transthoracic echocardiography and myocardial perfusion scintigraphy were performed in all participants. Presence of microvascular complications was also recorded. RESULTS: Overall, 51 patients had decreased estimated glomerular filtration rate and/or abnormal albuminuria, 24 had diabetic retinopathy, 22 had lower-extremity sensory neuropathy, and 67 (42.7%) patients had one or more of these microvascular complications (i.e., combined endpoint). After stratifying patients by LAVI, those with LAVI ≥32 ml/m(2) had a greater prevalence of microvascular complication, lower left ventricular (LV) ejection fraction, higher LV mass index and higher E/e' ratio than those with LAVI <32 ml/m(2). Logistic regression analyses revealed that microvascular complications (singly or in combination) were associated with increased LAVI, independently of age, sex, diabetes duration, hemoglobin A1c, hypertension, LV-ejection fraction, LV mass index and the E/e' ratio. CONCLUSIONS: These results indicate that microvascular diabetic complications are associated with increased LAVI in well-controlled type 2 diabetic patients with preserved systolic function and free from ischemic heart disease, independently of multiple potential confounders.

Nonalcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in patients with type 2 diabetes.

OBJECTIVE: Data on cardiac function in patients with nonalcoholic fatty liver disease (NAFLD) are limited and conflicting. We assessed whether NAFLD is associated with abnormalities in cardiac function in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 50 consecutive type 2 diabetic individuals without a history of ischemic heart disease, hepatic diseases, or excessive alcohol consumption, in whom NAFLD was diagnosed by ultrasonography. A tissue Doppler echocardiography with myocardial strain measurement was performed in all patients. RESULTS: Thirty-two patients (64%) had NAFLD, and when compared with the other 18 patients, age, sex, BMI, waist circumference, hypertension, smoking, diabetes duration, microvascular complication status, and medication use were not significantly different. In addition, the left ventricular (LV) mass and volumes, ejection fraction, systemic vascular resistance, arterial elasticity, and compliance were also not different. NAFLD patients had lower e' (8.2 ± 1.5 vs. 9.9 ± 1.9 cm/s, P < 0.005) tissue velocity, higher E-to-e' ratio (7.90 ± 1.3 vs. 5.59 ± 1.1, P < 0.0001), a higher time constant of isovolumic relaxation (43.1 ± 10.1 vs. 33.2 ± 12.9 ms, P < 0.01), higher LV-end diastolic pressure (EDP) (16.5 ± 1.1 vs. 15.1 ± 1.0 mmHg, P < 0.0001), and higher LV EDP/end diastolic volume (0.20 ± 0.03 vs. 0.18 ± 0.02 mmHg, P < 0.05) than those without steatosis. Among the measurements of LV global longitudinal strain and strain rate, those with NAFLD also had higher E/global longitudinal diastolic strain rate during the early phase of diastole (E/SR(E)). All of these differences remained significant after adjustment for hypertension and other cardiometabolic risk factors. CONCLUSIONS: Our data show that in patients with type 2 diabetes and NAFLD, even if the LV morphology and systolic function are preserved, early features of LV diastolic dysfunction may be detected.

[Coronary embolus and acute myocardial infarction in a patient with dilated cardiomyopathy and chronic atrial fibrillation]. / Infarto miocardico transmurale ad eziologia embolica in un paziente con cardiomiopatia dilatativa e fibrillazione atriale permanente.

We report the case of an acute myocardial infarction due to coronary embolism in a patient with dilated cardiomyopathy and permanent atrial fibrillation. The patient underwent thrombectomy and stenting. The authors discuss the acute treatment in this clinical situation and the problem of dual antiplatelet therapy in patients with an indication for long-term oral anticoagulation undergoing percutaneous coronary intervention and stenting.