Novel Insights into the Pathobiology of Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction.

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common cause of pulmonary hypertension (PH) worldwide and is strongly associated with adverse clinical outcomes. The American Heart Association recently highlighted a call to action regarding the distinct lack of evidence-based treatments for PH due to poorly understood pathophysiology of PH attributable to HFpEF (PH-HFpEF). Prior studies have described cardio-physiological mechanisms to explain the development of isolated postcapillary PH (ipc-PH); however, the consequent increased pulmonary vascular (PV) resistance (PVR) may lead to the less understood and more fatal combined pre- and postcapillary PH (cpc-PH). Metabolic disease and inflammatory dysregulation have been suggested to predispose cpc-PH, yet the molecular mechanisms are unknown. Although PH-HFpEF has been studied to partly share vasoactive neurohormonal mediators with primary pulmonary arterial hypertension (PAH), clinical trials that have targeted these pathways have been unsuccessful. The increased mortality of PH-HFpEF patients necessitates further study into viable mechanistic targets involved in disease progression. We aim to summarize the current pathophysiological and clinical understanding of PH-HFpEF, highlight the role of known molecular mechanisms in the progression of PV disease, and introduce a novel concept that lipid metabolism may be attenuating and propagating PH-HFpEF.

The Efficacy of Cardiac Myosin Inhibitors Versus Placebo in Patients With Symptomatic Hypertrophic Cardiomyopathy: A Meta-Analysis and Systematic Review.

We aimed to assess the overall clinical impact of cardiac myosin inhibitors in hypertrophic cardiomyopathy (HCM). We performed a meta-analysis of published trials assessing the effect of cardiac myosin inhibitors (mavacamten and aficamten) on resting and Valsalva left ventricular outflow tract (LVOT) gradients and functional capacity in symptomatic HCM. The co-primary outcomes were mean percent change (mean difference [MD]) from baseline in LVOT gradient at rest and Valsalva LVOT gradient and the proportion of patients achieving New York Heart Association class improvement ≥1. The secondary outcomes included the mean percent change from baseline N-terminal pro-B-type natriuretic peptide, troponin I, and left ventricular ejection fraction (LVEF). A total of 4 studies (all randomized controlled trials, including 3 mavacamten-focused and 1 aficamten-focused trials) involving 463 patients were included in the meta-analysis. Compared with placebo, the cardiac myosin inhibitor group demonstrated statistically significant differences in the baseline percent change in mean LVOT gradient at rest (MD -62.48, confidence interval [CI] -65.44 to -59.51, p <0.00001) and Valsalva LVOT gradient (MD -54.21, CI -66.05 to -42.36, p <0.00001) and the proportion of patients achieving New York Heart Association class improvement ≥1 (odds ratio 3.43, CI 1.90 to 6.20, p <0.0001). Regarding the secondary outcomes, the intervention group demonstrated statistically significant reductions in mean percent change from baseline in N-terminal pro-B-type natriuretic peptide (MD -69.41, CI -87.06 to -51.75, p <0.00001), troponin I (MD, -44.19, CI -50.59 to -37.78, p <0.00001), and LVEF (MD -6.31, CI -10.35, -2.27, p = 0.002). In conclusion, cardiac myosin inhibitors may confer clinical and symptomatic benefits in symptomatic HCM at the possible expense of LVEF. Further trials with large sample sizes are needed to confirm our findings.

A profile on the CardioMEMS HF system in the management of patients with early stages of heart failure: an update.

INTRODUCTION: Over the past decade, there have been noteworthy advances in the evaluation and treatment of heart failure (HF). Despite an improved understanding of this chronic disease, HF is still one of the leading causes of morbidity and mortality in the United States and worldwide. Decompensation and rehospitalization of HF patients remain an integral problem in disease management, with significant economic implications. Remote monitoring systems have been developed to detect HF decompensation early and address it before hospitalization. The CardioMEMS HF system is a wireless pulmonary artery (PA) monitoring system that detects changes in PA pressure and transmits data to the healthcare provider. As changes in PA pressures occur early during HF decompensation, the CardioMEMS HF system allows providers to institute timely changes in HF medical therapies to alter the course of the decompensation. The use of the CardioMEMS HF system has been shown to reduce HF hospitalization and improve quality of life. AREAS COVERED: This review will focus on the available data supporting the expanded utilization of the CardioMEMS system in patients with HF. EXPERT OPINION: The CardioMEMS HF system is a relatively safe and cost-effective device that reduces the incidence of HF hospitalization and qualifies as intermediate-to-high value medical care.

Paraoxonases at the Heart of Neurological Disorders.

Paraoxonase enzymes serve as an important physiological redox system that participates in the protection against cellular injury caused by oxidative stress. The PON enzymes family consists of three members (PON-1, PON-2, and PON-3) that share a similar structure and location as a cluster on human chromosome 7. These enzymes exhibit anti-inflammatory and antioxidant properties with well-described roles in preventing cardiovascular disease. Perturbations in PON enzyme levels and their activity have also been linked with the development and progression of many neurological disorders and neurodegenerative diseases. The current review summarizes the available evidence on the role of PONs in these diseases and their ability to modify risk factors for neurological disorders. We present the current findings on the role of PONs in Alzheimer's disease, Parkinson's disease, and other neurodegenerative and neurological diseases.

Brain-type natriuretic peptide levels and invasive hemodynamic parameters in dialysis dependent patients.

BACKGROUND: Pulmonary hypertension (PH) is associated with increased mortality in patients with end-stage renal disease (ESRD). The prevalence of PH within ESRD as measured by right heart catheterization (RHC) is poorly described, and the correlation of BNP to pulmonary artery pressure (PAP) is unknown. METHODS: The renal transplant database at our center was used to identify adult ESRD patients from July 2013 to July 2015 who had a plasma BNP level measurement and invasive hemodynamic assessment by RHC within a 1-month period. Pulmonary hypertension was defined as a mean pulmonary artery pressure (PAP) ≥ 25 mmHg. Multivariate linear regression analysis was used to identify correlations between BNP and RHC parameters. To estimate the utility of BNP in the screening of PH, a receiver-operating characteristic (ROC) curve was generated. RESULTS: Eighty-eight patients were included in the study of which 43 had PH. Compared to patients without PH, BNP was significantly higher within the PH cohort (1619 ± 2602 pg/ml vs. 352 ± 491 pg/ml). A statistically significant association (r [86] = 0.60, p<0.001) between plasma BNP and mean PAP was identified. ROC curve indicated an acceptable predictive value of BNP in PH with a c-statistic of 0.800 (95% CI 0.708 - 0.892). CONCLUSIONS: In ESRD patients being considered for renal transplantation, PH is highly prevalent and BNP levels are elevated and significantly correlated with higher PAP. BNP may be a useful non-invasive marker of PH in these patients.

Endothelin 1 Is Associated with Heart Failure Hospitalization and Long-Term Mortality in Patients with Heart Failure with Preserved Ejection Fraction and Pulmonary Hypertension.

BACKGROUND: The prevalence of pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is increasing. We aim to study the role of big endothelin 1 (Big ET1), endothelin 1 (ET1), and neprilysin (NE) in HFpEF with PH. METHOD: This was a single center prospective cohort study including 90 HFpEF patients; 30 with no PH, 30 with postcapillary PH, and 30 with combined post- and precapillary PH. After enrollment, pulmonary venous and pulmonary arterial samples of Big ET1, ET1, and NE were collected during right heart catheterization. Subjects were then followed long term for adverse outcomes which included echocardiographic evidence of right ventricular dysfunction, heart failure hospitalization, and all-cause mortality. RESULTS: Patients with HFpEF-PH were found to have increased ET1 in pulmonary veins (endothelin from the wedge; ET1W) compared to controls (2.3 ± 1.4 and 1.6 ± 0.9 pg/mL, respectively). ET1W levels were associated with both PH (OR 2.7, 95% CI 1.5-4.7, p = 0.01) and pulmonary vascular resistance (OR 1.6, 95% CI 1.04-2.3, p = 0.03). No evidence of right ventricular dysfunction was observed after 1 year of follow-up. ET1W (OR 1.8, 95% CI 1.2-2.6, p = 0.01) and ET1 gradient (ET1G; OR 1.4, 95% CI 1.04-2, p = 0.03) were predictive of 1-year hospitalization. ET1G ≥0.2 pg/mL was associated with long-term mortality (log-rank 4.8, p = 0.03). CONCLUSION: In HFpEF patients, ET1W and ET1G are predictive of 1-year heart failure hospitalization, while elevated ET1G levels were found to be associated with long-term mortality in HFpEF. This study highlights the role of ET1 in developing PH in HFpEF patients and also explores the potential of ET1 as a prognostic biomarker.

Pre-operative right ventricular echocardiographic parameters associated with short-term outcomes and long-term mortality after CABG.

Background This analysis aims to assess the prognostic value of pre-operative right ventricular echocardiographic parameters in predicting short-term adverse outcomes and long-term mortality after coronary artery bypass graft (CABG). Methods Study design: Observational retrospective cohort. Pre-operative echocardiographic data, perioperative adverse outcomes (POAO) and long-term mortality were retrospectively analyzed in 491 patients who underwent isolated CABG at a single academic center between 2006 and 2014. Results Average age of enrolled subjects was 66 ± 11.5 years with majority being male (69%). 227/491 patients had 30 days POAO (46%); most common being post-operative atrial fibrillation (27.3%) followed by prolonged ventilation duration (12.7%). On multivariate analysis, left atrial volume index ≥42 mL/m2 (LAVI) (OR (95% CI): 1.98 (1.03-3.82), P = 0.04), mitral E/A >2 (1.97 (1.02-3.78), P = 0.04), right atrial size >18 cm2 (1.86 (1.14-3.05), P = 0.01), tricuspid annular plane systolic excursion (TAPSE) <16 mm (1.8 (1.03-3.17), P = 0.04), right ventricular systolic pressure (RVSP) ≥36 mmHg (pulmonary hypertension) (1.6 (1.03-2.38), P = 0.04) and right ventricle myocardial performance index (RVMPI) >0.55 (1.58 (1.01-2.46), P = 0.04) were found to be associated with increased 30-day POAO. On 3.5-year follow-up, cumulative survival was decreased in patients with myocardial performance index (MPI) ≥0.55 (log rank: 4.5, P = 0.034) and in patients with mitral valve E/e' ≥14 (log rank: 4.9, P = 0.026). Conclusion Pre-operative right ventricle dysfunction (RVD) is associated with increased perioperative complications. Furthermore, pre-operative RVD and increased left atrial pressures are associated with long-term mortality post CABG.

Practical echocardiographic approach for risk stratification of patients with acute pulmonary embolism.

Acute pulmonary embolism remains a common cause of mortality. Early diagnosis and appropriate risk stratification is necessary to individualize treatment strategy. Computed tomography scan of the pulmonary arteries is routinely used to diagnose acute pulmonary embolism and in some cases is useful to assess right ventricular dilation. In patients with acute pulmonary embolism, right ventricular dilation and dysfunction indicates a high-risk situation where immediate administration of thrombolytic agent, catheter-directed thrombolysis, or surgical embolectomy could be considered. A bedside 2D echocardiogram at the time of presentation could provide additional morphological, functional, and hemodynamic parameters including right ventricular dilation, McConnell's sign, reduced tricuspid annular plane systolic excursion (TAPSE), interventricular septal flattening, abnormal right ventricular hemodynamics and in rare cases thrombi in the inferior vena cava, right atrium or ventricle en route to pulmonary arteries may also be visualized. This additional information is useful for selection of appropriate treatment modality. Thus, our objective is to provide a practical echocardiographic approach for risk stratification of patients with acute pulmonary embolism.

In vivo assessment of arterial stiffness in the isoflurane anesthetized spontaneously hypertensive rat.

BACKGROUND: Rodent models are increasingly used to study the development and progression of arterial stiffness. Both the non-invasive Doppler derived Pulse Wave Velocity (PWV) and the invasively determined arterial elastance index (EaI) have been used to assess arterial stiffness in rats and mice, but the need for anesthetic agents to make these in vivo estimates may limit their utility. Thus, we sought to determine: 1) if known differences in arterial stiffness in spontaneously hypertensive rats (SHR) are detectable by PWV and EaI measurements when made under isoflurane anesthesia, and 2) if these two uniquely acquired assessments of arterial elasticity correlate. METHODS: We obtained PWV and EaI measurements in isoflurane anesthetized young and old SHRs, which are known to have significant differences in arterial stiffness. Doppler pulse waves were recorded from carotid and iliac arteries and the distance (D) between probe applantation sites was recorded. Simultaneously, an EKG was obtained, and the time intervals between the R-wave of the EKG to the foot of the Doppler waveforms were measured and averaged over three cardiac cycles. Pulse-transit time (T) of the carotid to iliac artery was determined, and PWV was calculated as Distance (D)/Time (T), where D = the distance from the carotid to the iliac notch and T = (R to iliac foot) - (R to carotid foot). EaI was subsequently determined from pressure volumes loops obtained via left ventricle catheterization. RESULTS: PWV and EaI were found to be significantly faster in the older rats (13.2 ± 2.0 vs. 8.0 ± 0.8 m/sec, p < 0.001; 120 ± 20 vs. 97 ± 16 mmHg/µl/g, p <0.05). Bland-Altman analyses of intra- and inter-observer measures demonstrate a statistically significant relationship between readings (p < 0.0001). PWV and EaI measurements were found to be significantly and positively correlated with a correlation coefficient of 0.53 (p < 0.05). CONCLUSION: Our study suggests that isoflurane administration does not limit Doppler PWV or EaI measures in their ability to provide accurate, in vivo assessments of relative arterial stiffness in isoflurane anesthetised SHR rats. Furthermore, PWV data obtained in these rats correlate well with invasively determined EaI.

Prevalence and factors associated with left ventricular remodeling in renal artery stenosis.

The objective of this study is to evaluate the prevalence, geometric patterns, and factors associated with left ventricular remodeling in patients with renal artery stenosis (RAS). Demographic, clinical, and echocardiographic data were assessed in 77 patients with RAS prior to endovascular stenting. The left ventricular mass index (LVMI) and relative wall thickness were calculated using American Society of Echocardiography (ASE) recommendations. Patients were classified based on LVMI and relative wall thickness into four ventricular remodeling patterns: normal geometry, concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). Logistic regression was done to investigate the determinants of the different ventricular remodeling patterns. Mean LVMI and relative wall thickness were 118 ± 40 g/m(2) and 0.45 ± 0.1. Left ventricular hypertrophy was observed in 65%. CH was the most prevalent geometric pattern of remodeling (normal, 16.9%; CR, 18.2%; CH, 40%; EH, 24.6%). Thirty (39%) patients had an abnormal LV systolic function (ejection fraction <55%), with 14 (46%) of them having eccentric hypertrophy. Independent predictor of EH was glomerular filtration rate (odds ratio [OR], 0.943; confidence interval [CI], 0.899-0.989; P = .01). Systolic elevation of blood pressure (OR, 1.030; CI, 1.003-1.058; P = .03) was associated with CH, and elevated diastolic blood pressure was associated with CR (OR, 0.927; CI, 0.867-0.992; P = .02). Patients with RAS have a high prevalence of left ventricular remodeling and LVH. Even though CH was the most prevalent pattern of left ventricular remodeling, EH was commonplace and was associated with renal dysfunction and heart failure.

Giant interatrial septal aneurysm mimicking a left atrial mass.

Interatrial septal aneurysm (IASA) consists of redundant atrial septal tissue, which bulges into either the left or the right atrium. The clinical implications of this entity are not entirely clear; however, if it is associated with other cardiac abnormalities such as patent foramen ovale and atrial septal defects. It may assume significance by increasing the risk of cardioembolic events such as stroke. We present a case of an individual with giant IASA detected by transesophageal echocardiography, which was mimicking a left atrial mass on transthoracic echocardiography. This case emphasizes the superiority of transesophageal imaging over transthoracic echocardiography for this clinical entity.

The diagnostic accuracy of Doppler echocardiography in assessment of pulmonary artery systolic pressure: a meta-analysis.

BACKGROUND: Transthoracic echocardiography is commonly used to estimate pulmonary arterial systolic pressure (PASP) and to diagnose pulmonary hypertension (PH). However, some recent studies have questioned the accuracy of Doppler echocardiography (DE) in the assessment of PASP. The present meta-analysis was performed to estimate the accuracy, sensitivity, and specificity of DE in the assessment of PASP. METHODS: A literature search and data extraction of English and non-English articles reported from May 1984 to January 2009 was performed independently by 2 investigators using MEDLINE and EMBASE databases. Articles were included if they compared DE with right heart catheterization (RHC) in the assessment of PASP. Nine articles met our criteria and were included in our meta-analysis. We conducted a meta-analysis of the results of these articles using fixed- and random-effect models to estimate the accuracy, sensitivity, and specificity of DE in the assessment of PASP. RESULTS: The correlation between PASP estimated by DE and RHC ranged from (r = 0.65, P < 0.001) to (r = 0.97, P < 0.001). The pooled sensitivity, specificity, and accuracy of DE for the diagnosis of PH were 88% (95% confidence interval [CI], 84-92%), 56% (95% CI, 46-66%), and 63% (95% CI, 53-73%), respectively. CONCLUSION: DE is a useful noninvasive modality to screen for PH and can reliably determine whether PASP is normal, mildly elevated, or markedly elevated. However, abnormal results from DE need to be confirmed by RHC.

Post-reperfusion syndrome during renal transplantation: a retrospective study.

Post-reperfusion syndrome (PRS) is a serious, widely reported complication following the reperfusion of an ischemic tissue or organ. We sought to determine the prevalence, risk factors and short-term outcomes of PRS related renal transplantation. We conducted a retrospective, case-control study of patients undergoing renal transplantation between July 2006 and March 2008. Identification of PRS was based on a drop in mean arterial pressure by at least 15% within 5 minutes of donor kidney reperfusion. Of the 150 consecutive renal transplantations reviewed, 6 patients (4%) met criteria for post-reperfusion syndrome. Univariate analysis showed that an age over 60, diabetes mellitus, Asian race, and extended criteria donors increased the odds of developing PRS by 4.8 times (95% CI [1.2, 20]; P=.0338), 4.5 times (95% CI [1.11, 18.8]; P=.0378), 35.5 times (95% CI [3.94, 319.8]; P=0.0078) and 9.6 times (95% CI [1.19, 76.28] P=0.0115) respectively. Short term follow-up revealed increased graft failure rate within 6 months (6% vs. 16% P=0.0125) and almost twice the number of hospital days post-transplant in PRS cohorts (5.43 ± 2.29 vs. 10.8 ± 7.29 P=<0.0001). Despite limited reporting, PRS appears to be a relatively common complication of renal transplantation and is associated with increase morbidity.

Practical considerations for the pharmacotherapy of pulmonary arterial hypertension.

Pulmonary arterial hypertension is a devastating disease. Before the 1990s, when pharmacologic treatment was finally approved, only supportive therapy was available, consisting of anticoagulation, digoxin, diuretics, and supplemental oxygen. Calcium channel blocker therapy was also an option, but only a small percentage of patients respond to it. However, starting with epoprostenol in 1996, the number of drugs approved to treat pulmonary arterial hypertension increased. Three distinct classes of drugs were developed based on the pathophysiology of the disease: the prostanoids, endothelin-1 receptor antagonists, and phosphodiesterase type 5 inhibitors. The prostanoids are administered either parenterally or by inhalation to replace the lack of prostacyclin within the pulmonary arterial vasculature. The endothelin-1 receptor antagonists were the first class of oral drugs to be developed, but drug interactions and adverse effects are prominent with this class. The phosphodiesterase type 5 inhibitors increase the second messenger cyclic guanosine monophosphate (GMP) that is induced by nitric oxide stimulation. All of the drugs within these three classes are distinct in and of themselves, and their clinical use requires in-depth knowledge of pulmonary arterial hypertension and its pathophysiology. Because these drugs have different mechanisms of action, combination therapy has shown promise in patients with severe disease, although data are still lacking. This article should serve as a practical guide for clinicians who encounter patients with pulmonary arterial hypertension and the drugs used for the treatment of this devastating disease.

Cardiovascular antioxidant therapy: a review of supplements, pharmacotherapies, and mechanisms.

Oxidant stress plays an important role in the pathogenesis of atherosclerosis. In the late 1980s, biological studies demonstrated that oxygen-free radicals oxidize low-density lipoprotein-cholesterol, resulting in the creation of foam cells and inciting the cascade of biological events that ultimately result in the formation of atherosclerosis. In vitro studies showed the ability of antioxidant vitamins to scavenge free radicals and block the oxidation of low-density lipoprotein. This data was supported in vivo by early observational studies suggesting the benefit of antioxidants, particularly vitamin E, in the prevention of coronary artery disease. On the basis of these studies, the use of antioxidant supplements by the general population increased substantially and became a multibillion dollar industry. Despite strong biological evidence and promising observational data, more rigorous scientific evaluation did not support a causational relationship between vitamin supplements and lowering coronary artery disease risk. Several prospective, double-blind, placebo-controlled trials showed no benefit and possibly harmful effects. Therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and statins, which are known to have benefit in preventing and treating atherosclerosis by reducing blood pressure and cholesterol, also have a "pleiotropic" effect in reducing the formation of reactive oxygen species (ROS). Advances in molecular biology and the study of ROS led to a better understanding of the mechanisms that govern their production and role in atherogenesis. This progress identified unforeseen pathways by which these drugs favorably alter the balance in ROS production, and have raised possibilities for future targeted therapies in the prevention of atherosclerosis.

Endovascular therapy for radiation-induced pulmonary artery stenosis: a case report and review of the literature.

Although pulmonary artery stenosis and its treatment has been well characterized in pediatric populations, its diagnosis and even how to determine the significance of a stenosis can be difficult and optimal management is currently unknown. This case report and review of the literature outlines how we successfully diagnosed, evaluated, and stented a patient with radiation induced pulmonary artery stenosis. This case further adds support to a very limited data pool suggesting that percutaneous angioplasty of pulmonary artery stenosis may be a safe and effective treatment option for this unique patient population.

A novel approach to standard techniques in the assessment and quantification of the interventricular systolic relationship.

BACKGROUND: Blood flow between the right and left ventricles is subject to the continuity equation and systolic ventricular interdependence. Quantification of this relationship might aid in understanding inter-ventricular function. The purpose of this study was to evaluate and quantify ventricular interdependence by directly comparing right and left ventricular systolic function though echocardiographic surrogates of right and left ventricular systolic function such as MAPSE, TAPSE, RV TVI and LV TVI. METHODS: This study prospectively evaluated 51 healthy participants (mean age, 41 ± 17 years) by resting echocardiography. In addition to standard measurements, tricuspid annular plane of systolic excursion, (TAPSE), mitral annular plane of systolic excursion (MAPSE), and the peak annulus systolic velocity of the right ventricular (RVs) and left ventricular (LVs) free walls were measured by M-mode and pulsed wave Doppler tissue echocardiography and further evaluated for variance across age, gender, and body surface area. RESULTS: TAPSE (22.1 ± 2.9 mm) was over 54.5% greater than MAPSE (14.3 ± 2.6 mm) and RVs was 64.4% greater than LVs. The LV to RV systolic relationship measured by MAPSE/TAPSE and LVs/RVs ratios were 0.66 ± 0.14 and 0.76 ± 0.21 respectively. These values were not significantly affected by age, gender or body surface area (BSA). CONCLUSION: MAPSE/TAPSE and LVs/RVs ratios appear stable across age, gender, and BSA potentially making them good surrogates of systolic ventricular relationship and interdependence.

Live 3D TEE demonstrates and guides the management of prosthetic mitral valve obstruction.

A 43-year-old woman, with a remote history of rheumatic mitral stenosis and a St. Jude prosthetic mitral valve replacement, presented with shortness of breath and palpitations, shortly after a long flight. On admission, atrial fibrillation with a rapid ventricular response was noted in the setting of a long history of noncompliance with her anticoagulation. Transesophageal echocardiography (TEE) demonstrated multiple laminated thrombi in the left atrial appendage. Live three-dimensional (3D) TEE confirmed this diagnosis and demonstrated an immobile posterior leaflet of the mitral prosthesis, which had direct implications in her management. She successfully underwent surgery for mitral valve replacement, left atrial appendage ligation, and a Maze procedure on the following day. The multiple thrombi within the atrial appendage were confirmed intraoperatively and pannus formation was determined to be the etiology of the leaflet immobility.

A practical approach to the echocardiographic evaluation of diastolic function.

A number of recent community-based epidemiologic studies suggest that 40% to 50% of the cases of heart failure have preserved left ventricular systolic function. Although diastolic heart failure is often not well clinically recognized, it is associated with marked increases in morbidity and all-cause mortality. Doppler echocardiography has emerged as the principal clinical tool for the assessment of left ventricular diastolic function. Doppler mitral inflow velocity-derived variables remain the cornerstone of the evaluation of diastolic function. Pulmonary venous Doppler flow indices and mitral inflow measurements with Valsalva's maneuver are important adjuncts for differentiating normal and pseudonormal mitral inflow patterns. Unfortunately, these Doppler flow variables are significantly influenced by loading conditions and, therefore, the results from these standard techniques can be inconclusive. Recently, color M-mode and Doppler tissue imaging have emerged as new modalities that are less affected by preload and, thus, provide a strong complementary role in the assessment of diastolic function. This review will discuss the diastolic properties of the left ventricle, Doppler echocardiographic evaluation, and grading of diastolic dysfunction.