Ertugliflozin for Functional Mitral Regurgitation Associated With Heart Failure: EFFORT Trial.

BACKGROUND: The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction. METHODS: The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS: The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12). CONCLUSIONS: Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.

Effects of intensive blood pressure control on left ventricular hypertrophy in aortic valve disease.

BACKGROUND: Hypertension adds to the pressure overload on the left ventricle (LV) in combination with aortic valve (AV) disease, but the optimal blood pressure (BP) targets for patients with AV disease remain unclear. We tried to investigate whether intensive BP control reduces LV hypertrophy in asymptomatic patients with aortic stenosis (AS) or aortic regurgitation (AR). METHODS: A total of 128 hypertensive patients with mild to moderate AS (n = 93) or AR (n = 35) were randomly assigned to intensive therapy, targeting a systolic BP <130 mm Hg, or standard therapy, targeting a systolic BP <140 mm Hg. The primary end point was the change in LV mass from baseline to the 24-month follow-up. Secondary end points included changes in severity of AV disease, LV volumes, ejection fraction and global longitudinal strain (GLS). RESULTS: The treatment groups were generally well balanced regarding the baseline characteristics. The mean (±SD) age of the patients was 68 ± 8 years and 48% were men. The mean BP was 145 ± 12/81 ± 10 mm Hg at baseline. Medication at baseline was similar between the 2 groups. The 2 treatment strategies resulted in a rapid and sustained difference in systolic BP (P < .05). At 24-month, the mean systolic BP was 129 ± 12 mm Hg in the intensive therapy group and 135 ± 14 mm Hg in the standard therapy group. No patient died or underwent AV surgery during follow-up in either of the groups. LV mass was changed from 189.5 ± 41.3 to 185.6 ± 41.5 g in the intensive therapy group (P = .19) and from 183.8 ± 38.3 to 194.0 ± 46.4 g in the standard therapy group (P < .01). The primary end point of change in LV mass was significantly different between the intensive therapy and the standard therapy group (-3.9 ± 20.2 g vs 10.3 ± 20.4 g; P = .0007). The increase in LV mass index was also significantly greater in the standard therapy group (P = .01). No significant differences in secondary end points (changes in severity of AV disease, LV volumes, ejection fraction and GLS) were observed between the treatment groups. CONCLUSIONS: Among hypertensive patients with AV disease, intensive hypertensive therapy resulted in a significant reduction in LV hypertrophy, although progression of AV disease was similar between the treatment groups. CLINICAL TRIAL REGISTRATION: http://ClinicalTrials.gov (Number NCT03666351).

Neutrophil-to-Lymphocyte Ratio at Emergency Room Predicts Mechanical Complications of ST-segment Elevation Myocardial Infarction.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been proven to be a reliable inflammatory marker. A recent study reported that elevated NLR is associated with adverse cardiovascular events in patients with ST-segment elevation myocardial infarction (STEMI). We investigated whether NLR at emergency room (ER) is associated with mechanical complications of STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS: A total of 744 patients with STEMI who underwent successful primary PCI from 2009 to 2018 were enrolled in this study. Total and differential leukocyte counts were measured at ER. The NLR was calculated as the ratio of neutrophil count to lymphocyte count. Patients were divided into tertiles according to NLR. Mechanical complications of STEMI were defined by STEMI combined with sudden cardiac arrest, stent thrombosis, pericardial effusion, post myocardial infarction (MI) pericarditis, and post MI ventricular septal rupture, free-wall rupture, left ventricular thrombus, and acute mitral regurgitation during hospitalization. RESULTS: Patients in the high NLR group (> 4.90) had higher risk of mechanical complications of STEMI (P = 0.001) compared with those in the low and intermediate groups (13% vs. 13% vs. 23%). On multivariable analysis, NLR remained an independent predictor for mechanical complications of STEMI (RR = 1.947, 95% CI = 1.136-3.339, P = 0.015) along with symptom-to balloon time (P = 0.002) and left ventricular dysfunction (P < 0.001). CONCLUSION: NLR at ER is an independent predictor of mechanical complications of STEMI undergoing primary PCI. STEMI patients with high NLR are at increased risk for complications during hospitalization, therefore, needs more intensive treatment after PCI.

Angiotensin Receptor Neprilysin Inhibitor for Functional Mitral Regurgitation.

BACKGROUND: The morbidity and mortality of patients with functional mitral regurgitation (MR) remain high, but no pharmacological therapy has been proven effective. The hypothesis of this study was that sacubitril/valsartan would be superior to valsartan alone in improving functional MR via dual inhibition of the renin-angiotensin system and neprilysin. METHODS: In this double-blind trial, we randomly assigned 118 patients with heart failure with chronic functional MR secondary to left ventricular (LV) dysfunction to receive either sacubitril/valsartan or valsartan, in addition to standard medical therapy for heart failure. The primary end point was the change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, LV end-systolic volume, LV end-diastolic volume, and incomplete mitral leaflet closure area. RESULTS: The decrease in effective regurgitant orifice area was significantly greater in the sacubitril/valsartan group than in the valsartan group (-0.058±0.095 versus -0.018±0.105 cm2; P=0.032) in an intention-to-treat analysis including 117 (99%) patients. Regurgitant volume was also significantly decreased in the sacubitril/valsartan group in comparison with the valsartan group (mean difference, -7.3 mL; 95% CI, -12.6 to -1.9; P=0.009). There were no significant between-group differences regarding the changes in incomplete mitral leaflet closure area and LV volumes, with the exception of LV end-diastolic volume index ( P=0.044). We noted no significant difference in the change of blood pressure between the treatment groups, and 7 patients (12%) in the sacubitril/valsartan group and 9 (16%) in the valsartan group had ≥1 serious adverse events ( P=0.54). CONCLUSIONS: Among patients with secondary functional MR, sacubitril/valsartan reduced MR to a greater extent than did valsartan. Our findings suggest that an angiotensin receptor-neprilysin inhibitor might be considered for optimal medical therapy of patients with heart failure and functional MR. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02687932.

Mechanical and Pharmacological Revascularization Strategies for Prevention of Microvascular Dysfunction in ST-Segment Elevation Myocardial Infarction: Analysis from Index of Microcirculatory Resistance Registry Data.

OBJECTIVES: We aimed to identify mechanical and pharmacological revascularization strategies correlated with the index of microcirculatory resistance (IMR) in ST-elevation myocardial infarction (STEMI) patients. BACKGROUND: Microvascular dysfunction (MVD) after STEMI is correlated with infarct size and poor long-term prognosis, and the IMR is a useful analytical method for the quantitative assessment of MVD. However, therapeutic strategies that can reliably reduce MVD remain uncertain. METHODS: Patients with STEMI who underwent primary percutaneous coronary intervention (PCI) were enrolled. The IMR was measured with a pressure sensor/thermistor-tipped guidewire immediately after primary PCI. High IMR was defined as values ≥66th percentile of IMR in enrolled patients (IMR > 30.9 IU). RESULTS: A total of 160 STEMI patients were analyzed (high IMR = 54 patients). Clinical factors for Killip class (P=0.006), delayed hospitalization from symptom onset (P=0.004), peak troponin-I level (P=0.042), and multivessel disease (P=0.003) were associated with high IMR. Achieving final thrombolysis in myocardial infarction myocardial perfusion grade 3 tended to be associated with low IMR (P=0.119), whereas the presence of distal embolization was significantly associated with high IMR (P=0.034). In terms of therapeutic strategies that involved adjusting clinical and angiographic factors associated with IMR, preloading of third-generation P2Y12 inhibitors correlated with reducing IMR value (ß = -10.30, P < 0.001). Mechanical therapeutic strategies including stent diameter/length, preballoon dilatation, direct stenting, and thrombectomy were not associated with low IMR value (all P > 0.05), and postballoon dilatation was associated with high IMR (ß = 8.30, P=0.020). CONCLUSIONS: In our study, mechanical strategies were suboptimal in achieving myocardial salvage. Preloading of third-generation P2Y12 inhibitors revealed decreased IMR value, indicative of MVD prevention.

Impact of gender on heart failure presentation in non-obstructive hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease that represents a broad spectrum of morphologic features and clinical presentations. However, little is known about the impact of gender differences in heart failure (HF) development in non-obstructive HCM. We assessed clinical and echocardiographic parameters according to gender in patients with non-obstructive HCM and evaluated the impact of gender on HF presentation and cardiovascular (CV) outcomes in this population. We investigated 202 consecutive patients with non-obstructive HCM. Clinical parameters and conventional echocardiographic measurements including tissue Doppler measurements were evaluated and compared according to gender. Additionally, left ventricular (LV) deformation was assessed with global longitudinal strain (GLS) utilizing 2D speckle tracking software. Of the 202 patients (age = 63 ± 14 years, male: female = 141: 61), 51 patients (24.8%) presented with HF and female patients had HF more frequently (52.5% vs. 12.8%, P < 0.001). Females were older, had a higher prevalence of atrial fibrillation, had increased left atrial volume (LAV), and a higher ratio of early diastolic mitral inflow to early annular velocity (E/e') than males (70 ± 12 years vs. 59 ± 14 years, P < 0.001 for age; 51.4 ± 19.3 mL/m2 vs. 40.0 [Formula: see text] 13.4 mL/m2, P < 0.001 for indexed LAV; 17.2 [Formula: see text] 6.0 vs. 13.0 [Formula: see text] 4.3, P < 0.001 for E/e'). While LV maximal thickness and LV ejection fraction were comparable between men and women, GLS was decreased significantly in female patients (- 13.5 [Formula: see text] 3.4% vs. - 15.6 [Formula: see text] 4.0%, P = 0.001 for GLS). Even after adjusting for clinical factors, female was independently associated with HF presentation (Odd ratio 5.19, 95% CI 2.24-12.03, P < 0.001). During a median follow-up duration 34.0 months, 20 patients (9.9%) had HF hospitalization or CV death. In a multivariable analysis, female gender was associated with higher risk of the composite of HF hospitalization or CV death and HF hospitalization alone than male (Adjusted hazard ratio [HR] = 3.31, 95% CI 1.17-9.35, P = 0.024 for primary composite outcome of HF hospitalization or CV death; adjusted HR = 4.78, 95% CI 1.53-14.96, P = 0.007 for HF hospitalization). In patients with non-obstructive HCM, female patients presented with HF more frequently and showed a higher risk of CV events than male patients. LA volume, E/e' and LV mechanics were different between the genders, suggesting that these might contribute to greater susceptibility to HF in women with HCM.

Ivabradine-Induced Torsade de Pointes in Patients with Heart Failure Reduced Ejection Fraction.

Ivabradine is a selective inhibitor of the sinoatrial node "funny" current, prolonging the slow diastolic depolarization. As it has the ability to block the heart rate selectively, it is more effective at a faster heart rate. It is recommended for the treatment of heart failure reduced ejection fraction in the presence of beta-blocker therapy for the further reduction of the heart rate. However, previous reports have shown the association of Torsade de pointes (TdP) with concurrent use of ivabradine and drugs resulting in QT prolongation or blockage of the metabolic breakdown of ivabradine. In this article, we report two cases of patients with heart failure reduced ejection fraction who developed TdP after ivabradine use. Our report highlights the need to exercise caution with the administration of ivabradine in the presence of a reduced repolarization reserve, such as QT prolongation or metabolic insufficiency.

Normal reference values of diastolic strain rate in healthy individuals: Chronological trends and the comparison according to genders.

PURPOSE: Recently, the diastolic strain rate (DSR) utilizing speckle-tracking echocardiography has been proposed as a novel parameter for left ventricular diastolic function. We aimed to present normal reference data for those in a large-sized, selected group of healthy individuals. METHODS: The current study was a part of the Normal echOcardiogRaphic Measurements in KoreAn popuLation (NORMAL), a prospective nationwide survey from 23 centers in Korea. We analyzed 447 subjects (age 48 ± 15 years, 234 females) without any history of cardiovascular disease and presented the early and late DSRs (SRe and SRa , respectively) in a total and gender-/age-specified groups. RESULTS: Among the total subjects, the mean SRe and SRa were 1.6 ± 0.4 S-1 and 0.8 ± 0.3 S-1 , respectively. With increasing age, there were significant trends of decreasing SRe and increasing SRa . Although both gender groups showed comparable age, the female group presented significantly higher SRe compared to male subjects with age of 20-59 years, which diminished after the age of 60 years. However, the SRa was comparable between genders in all age groups. On multiple linear regression, age showed independent associations with both SRe (ß = -0.132, P = .010) and SRa (ß = 0.440, P < .001), whereas gender did not show any association with SRe or SRa . CONCLUSION: We present normal reference data of a novel parameter, DSR, in a large-sized selected group with healthy Korean subjects. Additionally, we present significant age-related changes both in SRe and SRa without the impact of their gender.

Prognostic Impact of Left Atrial Minimal Volume on Clinical Outcome in Patients with Non-Obstructive Hypertrophic Cardiomyopathy.

Maximal left atrial volume (LAVmax) has been suggested to be an important indicator of left ventricular (LV) diastolic function and a prognosticator in patients with hypertrophic cardiomyopathy (HCM). However, LAVmax can be influenced by LV longitudinal systolic function, which causes systolic descent of the mitral plane. We investigated the prognostic role of LAVmin in patients with HCM and tested if LAVmin is better than LAVmax in predicting clinical outcome in these patients. A total of 167 consecutive patients with HCM were enrolled (age = 64.7 ± 13.5 years, male: female = 120:47). Clinical parameters and conventional echocardiographic measurement including tissue Doppler measurement were evaluated. Left atrial maximal and minimal volumes were measured just before mitral valve opening and at mitral valve closure respectively using the biplane disk method. The relationship between LAVmin and the clinical outcome of hospitalization for heart failure (HF), stroke or all-cause mortality was evaluated. During a median follow-up of 25.0 ± 17.8 months, the primary end point of HF hospitalization, stroke or death occurred in 35 patients (21%). Indexed LAVmin was predictive of HF, stroke or death after adjustment for age, diabetes, hypertension, atrial fibrillation, LV ejection fraction, and E/e'in a multivariate analysis (P = 0.001). The model including indexed LAVmin was superior to the model including indexed LAVmax in predicting a worse outcome in patients with HCM (P = 0.02). In conclusion, LAVmin was independently associated with increased risk of HF, stroke, or mortality in patients with HCM and was superior to LAVmax in predicting clinical outcome in this population.

Regional cardiac dysfunction and outcome in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction.

AIMS: Global measures of left ventricular (LV) function, in particular LV ejection fraction (LVEF) and global myocardial strain measures, are powerful predictors of outcomes in patients with LV dysfunction, heart failure, or both. However, less is known about the relationship between regional myocardial function, especially that assessed by strain echocardiography and clinical prognosis. METHODS AND RESULTS: We studied 248 patients with LV dysfunction, heart failure, or both 5 days after first myocardial infarction (MI) from the VALIANT study. We assessed peak longitudinal strain (LS) via B-mode speckle tracking in 12 segments from the apical 4- and 2-chamber views and visually assessed LV wall motion score (WMS). We related these measures of regional myocardial function to each other and to clinical outcomes over 20-month follow-up. Normal reference values for segmental LS were derived from 50 healthy controls. Regional LS (-7.7%, Q1: -11.2%, Q3: -4.9%) was worse in segments with abnormal WMS, although was significantly impaired even in segments scored as normokinetic compared with normal controls (-10.4 ± 5.2% vs. -20.0 ± 7.6%, P < 0.001). In multivariable Cox proportional hazards models, each additional abnormal LS segment was associated with an increased risk of all-cause mortality (hazard ratio: 1.42, 95% confidence interval: 1.06-1.90, P = 0.02) even after adjustment for clinical covariates, including LVEF, LV end-systolic volume, and number of abnormal segments by WMS. CONCLUSION: In patients with LV dysfunction, heart failure, or both after MI, regional LS is significantly depressed even in segments with normal WMS, and this measure was related to adverse outcome.

Impact of area strain by 3D speckle tracking on clinical outcome in patients after acute myocardial infarction.

BACKGROUND: Three-dimensional (3D) speckle tracking echocardiography (STE) has been developed to overcome the limitations of two-dimensional (2D) STE and has been applied in the several clinical settings. However, no data exist about the prognostic value of 3DSTE-based strain on clinical outcome after myocardial infarction (MI). This study was designed to investigate the prognostic value of area strain (AS) by 3D speckle tracking in predicting clinical outcome after acute MI. METHODS: We assessed 96 patients (62±14 years, 72% male) with acute MI and who had undergone a coronary angiography. Clinical parameters and conventional echocardiographic measurements including the left atrial (LA) size and tissue Doppler measurements were evaluated. The global left ventricular (LV) AS was measured using 3D speckle tracking software. The relationship between the AS and clinical outcome of death or hospitalization for heart failure (HF) was assessed. RESULTS: During a median follow-up of 33±10 months, primary endpoint of death or HF occurred in 12 patients (12.5%). AS was predictive of death or HF after adjustment for age, gender, peak CK-MB, LA volume, LV end-systolic volume, LV mass, the ratio of early mitral inflow velocity to early mitral annular velocity, and LV ejection fraction in a multivariate Cox model (HR 1.23, 95% CI 1.02-1.47, P=.03). In addition, AS added incremental value in predicting death or heart failure on a model based on clinical and standard echocardiographic measures (P=.008). CONCLUSION: AS is independently associated with increased risk of death or HF after acute MI, suggesting that it can be a useful prognostic parameter in the patients following MI.

Relationship between J Waves and Vagal Activity in Patients Who Do Not Have Structural Heart Disease.

BACKGROUND: J waves are associated with increased vagal activity in patients with idiopathic ventricular fibrillation in several studies to date. However, the relationship between J waves and autonomic nervous activity in patients without structural heart disease remains under investigation. We investigated whether the presence of a J wave on the surface electrocardiogram (ECG) was related to increased vagal activity in patients without structural heart disease. METHODS: This retrospective study included 684 patients without structural heart disease who had undergone Holter ECG and surface ECG monitoring. Based on the presence of J waves on the surface ECG, patients were divided into two groups: those with J waves (group 1) and those without J waves (group 2). We compared heart rate variability (HRV), reflecting autonomic nervous activity, using 24-h Holter ECG between the groups. RESULTS: J waves were present in 92 (13.4%) patients. Heart rate (HR) in group 1 was significantly lesser than that in group 2 (P = 0.031). The ratio of low-frequency (LF) components to high-frequency (HF) components (LF/HF) in group 1 was significantly lower than that in group 2 (P = 0.001). The square root of the mean squared differences of successive NN intervals in group 1 was also significantly higher than that in group 2 (P = 0.047). In a multivariate regression analysis, male sex, HR, and LF/HF ratio remained independent determinants for the presence of J waves (P = 0.039, P = 0.036, and P < 0.001, respectively). CONCLUSION: In patients without structural heart disease, the presence of a J wave was associated with a slow HR, male sex, and increased vagal activity, independently.

The relationship between J wave on the surface electrocardiography and ventricular fibrillation during acute myocardial infarction.

We investigated whether the presence of J wave on the surface electrocardiography (sECG) could be a potential risk factor for ventricular fibrillation (VF) during acute myocardial infarction (AMI). We performed a retrospective study of 317 patients diagnosed with AMI in a single center from 2009 to 2012. Among the enrolled 296 patients, 22 (13.5%) patients were selected as a VF group. The J wave on the sECG was defined as a J point elevation manifested through QRS notching or slurring at least 1 mm above the baseline in at least two leads. We found that the incidence of J wave on the sECG was significantly higher in the VF group. We also confirmed that several conventional risk factors of VF were significantly related to VF during AMI; time delays from the onset of chest pain, blood concentrations of creatine phosphokinase and incidence of ST-segment elevation. Multiple logistic regression analysis demonstrated that the presence of J wave and the presence of a ST-segment elevation were independent predictors of VF during AMI. This study demonstrated that the presence of J wave on the sECG is significantly related to VF during AMI.

The Efficacy and Tolerability of Irbesartan/Amlodipine Combination Therapy in Patients With Essential Hypertension Whose Blood Pressure Were not Controlled by Irbesartan Monotherapy.

PURPOSE: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy. METHODS: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography. FINDINGS: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study. IMPLICATIONS: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).

Three-dimensional contrast echocardiography in assessing left ventricular diverticulum.

Congenital left ventricular (LV) diverticulum is a rare malformation that can be alone or in association with other congenital abnormalities. Since the several complications have been reported in association with LV diverticulum, as cardiac rupture, heart failure, and endocarditis, patients with LV diverticulum who are managed with conservative treatment would require regular checkups to ascertain the absence of such complications. We report a case of LV diverticulum in a 47-year-old man. He took the serial three-dimensional contrast echocardiography, which was reliable and readily available tool for defining LV diverticulum and monitoring the presence of complications.

Effect of the direct renin inhibitor aliskiren on left ventricular remodelling following myocardial infarction with systolic dysfunction.

AIMS: Direct renin inhibitors provide an alternative approach to inhibiting the renin-angiotensin-aldosterone system (RAAS) at the most proximal, specific, and rate-limiting step. We tested the hypothesis that direct renin inhibition would attenuate left ventricular remodelling in patients following acute myocardial infarction receiving stable, individually optimized therapy, including another inhibitor of the RAAS. METHODS AND RESULTS: We randomly assigned 820 patients between ∼2 and 8 weeks following acute myocardial infarction, with the left ventricular ejection fraction (LVEF) ≤45%, and regional wall motion abnormalities (≥20% akinetic area), to receive aliskiren (n = 423), titrated to 300 mg, or matched placebo (n = 397), added to the standard therapy. All patients were required to be on a stable dose of an ACE-inhibitor or ARB, and beta-blocker unless contraindicated or not tolerated. Echocardiograms were obtained at baseline, and following 26-36 weeks of treatment. The primary endpoint was change in left ventricular end-systolic volume from baseline to 36 weeks, and was evaluable in 329 patients in the placebo group and 343 patients in the aliskiren group. We observed no difference in the primary endpoint of end-systolic volume change between patients randomized to aliskiren (-4.4 ± 16.8 mL) or placebo (-3.5 ± 16.3 mL), or in secondary measures of end-diastolic volume, or LVEF. We also observed no differences in a composite endpoint of cardiovascular death, hospitalization for heart failure, or reduction in LVEF >6 points. There were more investigator reported adverse events in the aliskiren group, including hypotension, increases in creatinine and hyperkalaemia. CONCLUSION: Adding the direct renin inhibitor aliskiren to the standard therapy, including an inhibitor of the RAAS, in high-risk post-MI patients did not result in further attenuation of left ventricular remodelling, and was associated with more adverse effects. These findings do not suggest that dual RAAS blockade with aliskiren would provide additional benefit in these high-risk post-MI patients.

Association of Left Atrial Structure and Function With Heart Failure in Older Adults.

BACKGROUND: Limited data exist to characterize novel measures of left atrial (LA) structure and function in older adults without prevalent heart failure (HF). OBJECTIVES: The aim was to assess reference range of LA measures, their associations with N-terminal pro-B-type natriuretic-peptide (NT-proBNP) and the related risk for incident HF or death. METHODS: We analyzed LA structure (LA maximal [LAViMax] and minimal volume indexed by body surface area) and function (LA emptying fraction, LA reservoir, conduit, and contraction strain) in 4,901 participants from the ARIC (Atherosclerosis Risk In Communities) study (mean age 75 ± 5 years, 40% male, and 19% Black) without prevalent HF. We assessed sex-specific 10th and 90th percentile ARIC-based reference limits in 301 participants free of prevalent cardiovascular disease, and related LA measures to NT-proBNP and incident HF or death (median follow-up of 5.5 years) in the whole ARIC cohort. RESULTS: Approximately 20% of the overall population had LA abnormalities according to the ARIC-based reference limit. Each LA measure was associated with NT-proBNP and, except for LAViMax, with incident HF or death after multivariable adjustment (including left ventricular function and NT-proBNP). Results were consistent in participants with normal LAViMax (P for interaction > 0.05). LA measures were prognostic for both incident HF with preserved ejection fraction or death and incident HF with reduced ejection fraction or death. When added to HF risk factors and NT-proBNP (baseline C-statistics = 0.74) all LA measures, except for LAViMax, significantly enhanced the prognostic accuracy. CONCLUSIONS: Novel measures of LA structure and function, but not standard assessment by LAViMax, are associated with increased risk of incident HF or death regardless of measures of left ventricular function and NT-proBNP.

Impact of right atrial enlargement on clinical outcome in patients with atrial fibrillation.

Background: Left atrial (LA) remodeling is associated with adverse cardiovascular events, including heart failure (HF) and stroke in patients with atrial fibrillation (AF). However, there are limited data on the value of right atrial (RA) remodeling in this population. We investigated the prognostic role of RA enlargement in patients with non-valvular AF. Methods and results: We analyzed 254 consecutive patients (age = 69 ± 12years, male:female = 165:89, mean left ventricular ejection fraction = 58.0 ± 7.2%) with non-valvular AF who underwent two-dimensional echocardiography from a single center. RA and LA volumes were measured from apical views and indexed to the body surface areas (right atrial volume index [RAVI] and left atrial volume index [LAVI]) and RAVI > 30mL/m2 and LAVI > 34mL/m2 were considered as enlarged. The relationship between RA enlargement and composite clinical outcome of hospitalization for HF (HHF), stroke, systemic embolism, or death from any cause was assessed. Right atrial (RA) enlargement was associated with older age and more frequent prevalence of persistent or permanent AF. During a median follow-up of 47.1 months, 77 patients (30%) had experienced primary composite outcome. In a multivariable model, RA enlargement, but not LA enlargement, was independently associated with adverse clinical outcomes even after adjusting for clinical and echocardiographic factors {adjusted hazard ratio [HR], 1.90 [95% confidence interval (CI), 1.14-3.18], p = 0.014 for primary composite outcome; adjusted HR, 2.70 [95% CI, 1.27-5.67], p = 0.001 for HHF or all cause death}. Conclusion: RA enlargement was independently associated with an increased risk of HF, stroke, systemic embolization or death in patients with non-valvular AF, suggesting that RA volume can be helpful in assessing future cardiovascular risk in this population.

PRE-OPerative ECHOcardiograhy for prevention of cardiovascular events after non-cardiac surgery in intermediate- and high-risk patients: protocol for a low-interventional, mixed-cohort prospective study design (PREOP-ECHO).

BACKGROUND: Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery. METHODS: This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery. DISCUSSION: This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs. TRIAL REGISTRATION: The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.

Mechanical dyssynchrony after myocardial infarction in patients with left ventricular dysfunction, heart failure, or both.

BACKGROUND: Mechanical dyssynchrony is considered an independent predictor for adverse cardiovascular outcomes in patients with heart failure. However, its importance as a risk factor after myocardial infarction is not well defined. METHODS AND RESULTS: We examined the influence of mechanical dyssynchrony on outcome in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction who were enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) echocardiography study. B-mode speckle tracking with velocity vector imaging was used to assess ventricular synchrony in 381 patients who had image quality sufficient for analysis. Time to regional peak velocity and time to strain rate were measured among 12 left ventricular segments from the apical 4- and 2- chamber views, and the SDs between all 12 segments were used as a measure of dyssynchrony. The relationships between the SD of time to regional peak velocity and strain rate and clinical outcome of death or heart failure were assessed. In a multivariate Cox model adjusted for clinical and echocardiographic variables, the SD of time to peak velocity (hazard ratio per 10 ms, 1.10; 95% confidence interval, 1.02 to 1.18; P=0.010) and the SD of time to strain rate (hazard ratio per 10 ms, 1.16; 95% confidence interval, 1.06 to 1.27; P=0.001) were independent predictors of death or heart failure. CONCLUSIONS: Left ventricular dyssynchrony is independently associated with increased risk of death or heart failure after myocardial infarction, suggesting that contractile pattern may play a role in post-myocardial infarction prognosis.