Empagliflozin and Dapagliflozin Therapies Favorably Alter QRS-T Angle and Cardiac Repolarization Parameters in Patients with Heart Failure.

Recent randomized clinical trials demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT2is) reduces the risk of cardiac mortality due to sudden cardiac death and progressive pump failure in patients with heart failure (HF). Mechanisms underlying the potential anti-arrhythmic effects of SGLT2is are not well understood. We aimed to examine the effect of SGLT2i treatment on the frontal-plane QRS-T (f[QRS-T]) angle, a novel marker of myocardial repolarization and an independent predictor of adverse cardiac outcomes. The study included 106 patients with HF with reduced ejection fraction (HFrEF) who received an SGLT2i, empagliflozin, or dapagliflozin. All study participants underwent screening 12-lead electrocardiography (ECG) before and ∼90 days after treatment. We compared ECG repolarization parameters before and after treatment. During study enrollment, there were statistically significant decreases in the Tp-e/QT ratio (P ≤ .0001), Tp-e/corrected QT ratio (P = .0002), Tp-e interval (P < .0001), and f(QRS-T) angle (P = .04) in response to SGLT2i therapy. In addition, study participants experienced an improvement in functional capacity (2.06 ± 0.6 vs. 1.82 ± 0.6, P = .0001) and reduced N-terminal pro-b-type natriuretic peptide values. In this retrospective cohort study, SGLT2i therapy was associated with improved cardiac repolarization parameters in patients with HFrEF. More comprehensive studies are needed to evaluate the impact of SGLT2i on cardiac repolarization and its potential relation to cardiac arrhythmia and sudden cardiac death risk.

Prevention and treatment of hypertensive left ventricular hypertrophy.

PURPOSE OF REVIEW: Left ventricular (LV) hypertrophy (LVH) is a well recognized target organ adaptation to longstanding uncontrolled hypertension and other cardiovascular risk factors. It is also a strong and independent predictor of many cardiovascular disorders. RECENT FINDINGS: This focused review explores the current concepts in screening, diagnosis, prevention, and treatment of LVH in patients with hypertension. Currently, the primary screening and diagnostic tools for LVH are ECG and 2D echocardiography. Implementing machine learning in the diagnostic modalities can improve sensitivity in the detection of LVH. Lifestyle modifications, blood pressure control with antihypertensive therapy, and management of comorbidities aid in preventing and reversing LV remodeling. SUMMARY: LVH is a common and often silent complication of hypertension. Prevention and reversal of LV remodeling are crucial for cardiovascular risk reduction in patients with hypertension.

The complex interplay between diabetes mellitus and atrial fibrillation.

INTRODUCTION: A growing body of evidence suggests that diabetes mellitus (DM) is associated with an increased risk of new-onset atrial fibrillation (AF) and contributes to suboptimal arrhythmia control and poor prognosis in patients with AF. The high prevalence of AF among patients with DM is primarily attributed to common risk factors, shared pathophysiological mechanisms, and associated atrial remodeling and autonomic dysfunction. AREAS COVERED: This comprehensive review covers the current data on the role of DM in the development and prognosis of AF. In addition, we review the impact of anti-DM medications on AF prevention and the role of anticoagulation in patients with coexisting DM and AF. EXPERT OPINION: DM is independently associated with new-onset AF, and the coexistence of these two conditions contributes to poor outcomes, from reduced quality of life to increased risks of thromboembolic events, heart failure, and mortality. Despite this strong link, the current evidence is insufficient to recommend routine screening for AF in patients with DM. Although some observations exist on preventing AF with anti-DM medications, randomized controlled trials are warranted to explore the proposed benefits of novel anti-DM medicines in reducing the risk of incident AF.

Dimensionless index of the mitral valve for evaluation of degenerative mitral stenosis.

PURPOSE: Degenerative mitral stenosis (DMS) is an increasingly recognized cause of mitral stenosis. The goal of this study was to compare echocardiographic differences between DMS and rheumatic mitral stenosis (RMS), identify echocardiographic variables reflective of DMS severity, and propose a dimensionless mitral stenosis index (DMSI) for assessment of DMS severity. METHODS: This is a single-center, retrospective cohort study. We included patients with at least mild MS and a mean transmitral pressure gradient (TMPG) ≥4 mm Hg. Mitral valve area by the continuity equation (MVACEQ ) was used as an independent reference. The DMSI was calculated as follows: DMSI = VTILVOT / VTIMV. All-cause mortality data were collected retrospectively. RESULTS: A total of 64 patients with DMS and 24 patients with RMS were identified. MVACEQ was larger in patients with DMS (1.43 ± 0.4 cm2 ) than RMS (0.9 ± 0.3 cm2 ) by ~0.5 cm2 (P = <.001), and mean TMPG was lower in the DMS group (6.0 ± 2 vs 7.9 ± 3 mm Hg, P = .003). A DMSI of ≤0.50 and ≤0.351 was associated with MVACEQ ≤1.5 and MVACEQ ≤1.0 cm2 (P < .001), respectively. With the progression of DMS from severe to very severe, there was a significant drop in DMSI. There was a nonsignificant trend toward worse survival in patients with MVACEQ ≤1.0 cm2 and DMSI ≤0.35, suggesting severe stenosis severity. CONCLUSION: Our results show that TMPG correlates poorly with MVA in patients with DMS. Proposed DMSI may serve as a simple echocardiographic indicator of hemodynamically significant DMS.

Hypertension and diabetes mellitus: highlights of a complex relationship.

PURPOSE OF REVIEW: Herein, we provide a review of the recent literature on the epidemiological and pathophysiological relationship between hypertension (HTN) and diabetes mellitus, along with prognostic implications and current treatment concepts. RECENT FINDINGS: Diabetes mellitus affects ∼10% of US adults. The prevalence of HTN in adults with diabetes mellitus was 76.3% or 66.0% based on the definitions used by guidelines. There exist differences among major society guidelines regarding the definition of HTN and target blood pressure (BP) levels. Recent basic and clinical research studies have shed light on pathophysiologic and genetic links between HTN and diabetes mellitus. Randomized controlled trials over the past 5 years have confirmed the favorable BP and cardiovascular risk reduction by antidiabetic agents. SUMMARY: HTN and diabetes mellitus are 'silent killers' with rising global prevalence. The development of HTN and diabetes mellitus tracks each other over time. The coexistence of both clinical entities synergistically contributes to micro- and macro-vasculopathy along with cardiovascular and all-cause mortality. Various shared mechanisms underlie the pathophysiological relationship between HTN and diabetes mellitus. Moreover, BP reduction with lifestyle interventions and antihypertensive agents is a primary target for reducing cardiovascular risk among patients with HTN and diabetes mellitus.

First in human: the effects of biventricular pacing on cardiac output in severe pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) carries high morbidity and mortality despite available treatment options. In severe PAH, right ventricular (RV) diastolic pressure overload leads to interventricular septal bowing, hindering of left ventricular diastolic filling and reduced cardiac output (CO). Some animal studies suggest that pacing may mitigate this effect. We hypothesized that eliminating late diastole via ventricular pacing could improve CO in human subjects with severe PAH. Using minimal to no sedation, we performed transvenous acute biventricular (BiV) pacing and right heart catheterization in six patients with symptomatic PAH. Hemodynamic measurements were taken at baseline and during BiV pacing at various 20-ms intervals of V-V timing. We compared baseline CO to (1) CO while pacing the RV first by 80 ms (mimicking RV-only pacing), and then to (2) CO during pacing at the V-V timing that resulted in the highest CO. All participants were female, PASP 74 ± 14 mmHg, QRS duration 104 ± 20 ms. Compared with baseline, the CO decreased when the RV was paced first by 80 ms (7.2 ± 1.0 vs. 6.2 ± 1.1 L/min, p = 0.028). Pacing with optimal V-V timing produced CO similar to baseline (7.2 ± 1.0 vs. 7.4 ± 1.4, p = 0.92). Two patients (33%) met the predefined endpoint of a 15% increase in CO during pacing at the optimal V-V timing. In symptomatic PAH, V-V optimized acute BiV pacing does not consistently improve CO. However, acute BiV pacing did improve CO in a subset of this cohort. Further research is needed to identify predictors of response to cardiac resynchronization therapy in this population.

Left ventricular hypertrophy and hypertension.

Hypertension (HTN) is a major modifiable risk factor for cardiovascular disease (CVD) morbidity and mortality. The left ventricle (LV) is a primary target for HTN end-organ damage. In addition to being a marker of HTN, LV geometrical changes: concentric remodeling, concentric or eccentric LV hypertrophy (LVH) are major independent risk factors for not only CVD morbidity and mortality but also for all-cause mortality and neurological pathologies. Blood pressure control with lifestyle changes and antihypertensive agents has been demonstrated to prevent and regress LVH. Herein, we provide a comprehensive review of literature on the relationship between HTN and LV geometry abnormalities with a focus on diagnosis, prognosis, pathophysiological mechanisms, and treatment approaches.

Effect of fenofibrate on serum nitric oxide levels in patients with hypertriglyceridemia.

BACKGROUND: Fenofibrate, a peroxisome proliferator-activated receptor-α (PPARα) agonist, is used to treat patients with hypercholesterolemia and hypertriglyceridemia in order to reduce the risk of development of the atherosclerotic cardiovascular disease. However, it exerts pleiotropic effects beyond correcting atherogenic dyslipidemia to treat hypercholesterolemia. OBJECTIVES: The aim of this study was to investigate the potential effects of fenofibrate on endothelial function by analyzing the serum nitric oxide (NO) levels in patients with hypertriglyceridemia. MATERIAL AND METHODS: Lipid profiles and serum NO levels were assessed in 56 healthy adults aged 29 to 84 years, before and after 12 weeks of fenofibrate (250 mg/d; n = 30) or placebo (n = 26). Appropriate dietary suggestions for hypertriglyceridemia were made for all patients. This study was randomized, double-blind and placebo-controlled in design. RESULTS: Total cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and triglyceride levels significantly decreased; high-density lipoprotein (HDL) and NO levels significantly increased after 12 weeks of fenofibrate therapy. We observed a statistically significant correlation between the increase in serum NO levels and decrease in serum triglyceride levels (r = -0.42, p = 0.02) in the fenofibrate group. CONCLUSIONS: The positive effect of short-term fenofibrate treatments on vascular endothelial functions in patients with hypertriglyceridemia has been demonstrated by increasing the serum NO levels. Agents such as fenofibrate targeting PPARα-associated signaling pathways show promise as an alternative treatment of vascular dysfunction related to advanced age and hyperlipidemia.

Pathophysiology and Prevention of Heart Disease in Diabetes Mellitus.

Diabetes mellitus (DM) has become a public health problem worldwide, and it has large implications for cardiovascular disease (CVD). In this article, we discuss the etiology and pathophysiology of CVD in DM including the effects of abnormal glucose homeostasis, genetic factors, epigenetics, apoptosis, common pathophysiological mechanisms shared by both DM and CVD, and contributions of other comorbidities. We then cover the pathogenesis of both atherosclerotic disease and cardiomyopathy in relation to DM. Finally, we discuss the prevention of heart disease in DM with a focus on hypertension and dyslipidemia management, weight loss, lifestyle changes, antiplatelet therapy, and glycemic control.

Positive Predictive Value of Noninvasive Stress Testing Is Poor in the Real World.

Abnormal noninvasive stress test (NIST) findings do not always correlate with angiographically significant (luminal obstruction ≥50%) coronary artery disease. Positive predictive value (PPV) of NIST in the real clinical practice is not well known. The goal of this retrospective study was to determine the PPV of NIST and assess the factors affecting PPV in a US community hospital. This study included all consecutive patients (n = 355) who underwent invasive coronary angiography after a positive NIST within ~1-year duration at our institution. Three hundred twenty-four patients were included in the analysis after exclusion of 31 patients. Sixty percent of patients were female and mean age was 63.2 (SD 12.4). Myocardial perfusion imaging, echocardiogram (treadmill or dobutamine), and treadmill electrocardiogram were the tests of choice in 95% (n = 307), 4% (n = 14), and 1% (n = 3) of patients, respectively. Overall PPV of NIST was 36.4% (118/324). When patients were stratified by age (<50 years, 50-65 years, ≥65 years), older age groups had significantly higher PPV (<0.001). When patients were grouped by body mass index (<25, 25-30, ≥30), those in lower body mass index groups had higher PPV (P = 0.01). Stress echocardiogram had significantly higher PPV compared with myocardial perfusion imaging stress test (71% vs. 35%; P < 0.005). Stress test site (in-hospital vs. outpatient office) or specialty of interpreting physician did not significantly impact PPV. Multivariable logistic regression analysis revealed that older age, male sex, and total number of cardiac risk factors were significant determinants of higher PPV. Our single-center study revealed that overall PPV of NIST is poor (36.4%), more notably in young, female, or obese patients.

The Interaction of Cardiorespiratory Fitness With Obesity and the Obesity Paradox in Cardiovascular Disease.

Overweight and obesity are well-established risk factors for most cardiovascular diseases (CVD), including coronary heart disease (CHD), heart failure (HF), and atrial fibrillation. Despite the strong link between excess adiposity and risk of CVD, growing evidence has demonstrated an obesity paradox in patients with CVD. This phenomenon is characterized by a better prognosis in overweight and mildly obese CVD patients than their leaner counterparts. Moreover, the worst outcomes are often incurred by underweight CVD patients, followed by those of normal weight or severely obese. The obesity paradox is now a well-established phenomenon across different types of CVD, and it occurs regardless of age and ethnicity of patients, and severity of CVD. Physical inactivity and low cardiorespiratory fitness (CRF) have long been recognized as major risk factors for CVD. In contrast, high levels of physical activity (PA) and CRF largely neutralize the adverse effects of excess adiposity and other traditional CVD risk factors, including hypertension, metabolic syndrome, and type-2 diabetes. Higher CRF also results in better CVD outcomes across different BMI groups and significantly alters the obesity paradox in patients with HF and CHD. Prognostic benefits of overweight/obesity tend to be limited to unfit patients with HF and CHD, and the obesity paradox usually disappears with improved levels of CRF. Nevertheless, increased PA and exercise training, to maintain or improve CRF, are effective, safe, and proven strategies for primary and secondary prevention of CVD in all weight groups. In this review, we discuss the current concepts of individual and combined contributions of fatness and fitness to CVD risk and prognosis. We then examine the influence of fitness on the obesity paradox in individuals with CVD.

Hypertensive crisis: an update on clinical approach and management.

PURPOSE OF REVIEW: Here, we review current concepts on hypertensive crisis (HTN-C) with a focus on epidemiology, causes, pathophysiology and prognosis. We also offer a practical approach to the management of HTN-C. RECENT FINDINGS: HTN-C is characterized by a severe and abrupt increase in blood pressure (BP) with impending or progressive acute end-organ damage (EOD). HTN-C can be divided into hypertensive emergency (HTN-E) and hypertensive urgency (HTN-U) based on the presence or absence of acute EOD, respectively. Recent retrospective studies have demonstrated that emergency department (ED) referrals from an outpatient clinic or rapid BP-lowering strategies in the ED do not lead to improved outcomes in patients with HTN-U. SUMMARY: HTN-C can be a de-novo manifestation or a complication of essential or secondary HTN. The presence of acute EOD is a major poor prognostic indicator in HTN-C. The main objectives of the management of HTN-C are distinction of HTN-E from HTN-U and appropriate risk stratification, prevention or regression of acute EOD due to severely elevated BP, prevention of recurrence of HTN-C with an effective long-term management plan and avoidance of rapid lowering of BP except in some special circumstances. The majority of patients with asymptomatic HTN-U can be safely managed in the outpatient setting without exposing them to the risks of aggressive BP lowering. However, patients with HTN-E require hospitalization, prompt treatment and close monitoring.

Current Perspectives on Left Ventricular Geometry in Systemic Hypertension.

Hypertension (HTN) is a global health problem and a leading risk factor for cardiovascular disease (CVD) morbidity and mortality. The hemodynamic overload from HTN causes left ventricular (LV) remodeling, which usually manifests as distinct alterations in LV geometry, such as concentric remodeling or concentric and eccentric LV hypertrophy (LVH). In addition to being a common target organ response to HTN, LV geometric abnormalities are well-known independent risk factors for CVD. Because of their prognostic implications and quantifiable nature, changes in LV geometric parameters have commonly been included as an outcome in anti-HTN drug trials. The purpose of this paper is to review the relationship between HTN and LV geometric changes with a focus on (1) diagnostic approach, (2) epidemiology, (3) pathophysiology, (4) prognostic effect and (5) LV response to anti-HTN therapy and its impact on CVD risk reduction.

Diabetes mellitus and hypertension: a dual threat.

PURPOSE OF REVIEW: The following is a review of the current concepts on the relationship between hypertension (HTN) and diabetes mellitus with a focus on the epidemiology and cardiovascular prognostic implications of coexistent HTN and diabetes mellitus, shared mechanisms underlying both conditions and pathophysiology of increased risk of cardiovascular disease, treatment of HTN in individuals with diabetes mellitus, and effects of anti-diabetic medications on blood pressure (BP). RECENT FINDINGS: Diabetes mellitus and HTN often coexist in the same individual. They share numerous risk factors and underlying pathophysiologic mechanisms, most important of which are insulin resistance and inappropriate activation of the rennin-angiotensin-aldosterone system. Recently updated guidelines recommend a BP goal of 140/90 mmHg in most individuals with diabetes mellitus. A new class of anti-diabetic medications, sodium-glucose co-transporter 2 inhibitors, has shown favorable effects on BP. SUMMARY: HTN affects the majority of individuals with diabetes mellitus. Coexistence of diabetes mellitus and HTN, especially if BP is not well controlled, dramatically increases the risk of morbidity and mortality from cardiovascular disease. BP control is an essential part of management of patients with diabetes mellitus, because it is one of the most effective ways to prevent vascular complications and death.