Mitral Valve Prolapse With Mid-Late Systolic Mitral Regurgitation: Pitfalls of Evaluation and Clinical Outcome Compared With Holosystolic Regurgitation

OBJECTIVES: Mitral regurgitation (MR) of mitral valve prolapse predominates in late systole but may be holosystolic or purely mid-late systolic, but the impact of MR timing on MR left ventricular and left atrial consequences and outcome is unknown. Whether effective regurgitant orifice (ERO) by the flow convergence method is similarly linked to outcome in mid-late systolic MR and holosystolic MR is uncertain.

METHODS: We comprehensively and prospectively quantified MR in 111 patients with mitral valve prolapse and mid-late systolic MR and matched them to 90 patients with mitral valve prolapse and holosystolic MR for age, gender, atrial fibrillation, ejection fraction, and ERO (flow convergence).

RESULTS: Mid-late systolic MR versus holosystolic MR groups were well matched, including for comorbidity, blood pressure, and heart rate (all P>0.10). Mid-late systolic MR versus holosystolic MR caused similar color jet area, midsystolic regurgitant flow, and peak velocity (P>0.40). Despite identical ERO (0.25±0.15 versus 0.25±0.15 cm(2); P=0.53), the shorter duration of mid-late systolic MR (233±56 versus 426±50 ms; P<0.0001) yielded lower regurgitant volume (24.8±13.4 versus 48.6±25.6 mL; P<0.0001). MR consequences, systolic pulmonary pressure, and left ventricular and left atrial volume index (all P<0.001) were more benign in mid-late systolic MR versus holosystolic MR. Under medical management, fewer cardiac events (5 years: 15.8±4.6% versus 40.4±6.1%; P<0.0001) occurred in mid-late systolic MR versus holosystolic MR, requiring less mitral surgery. Multivariable analysis confirmed the independent association of mid-late systolic MR with benign consequences and outcomes (all P<0.01). Absolute ERO was not linked to outcome, in contrast to regurgitant volume.

CONCLUSIONS: MR of mitral valve prolapse that is purely mid-late systolic causes more benign consequences and outcomes than holosystolic MR. Assessment may be misleading because jet area and ERO by flow convergence appear similar to those of holosystolic MR. However, shorter MR yields lower regurgitant volume, consequences, and benign outcomes. Instantaneous ERO by flow convergence should be interpreted in context, and in mid-late systolic MR, regurgitant volume provides information more reflective of MR severity. Therefore, for clinical management and surgical referral, clinicians should carefully take into account the timing and consequences of MR.

PMID: 22388325

Characteristics and Clinical Significance of Angiographically Mild Lesions in Acute Coronary Syndromes

OBJECTIVES: The aim of this study was to assess whether residual nonculprit (NC) lesions, defined as visual diameter stenosis ≥30% after successful percutaneous coronary intervention, affect the rate of future events in patients with acute coronary syndromes. In patients with acute coronary syndromes, approximately one-half of recurrent events after percutaneous coronary intervention arise from untreated lesions.

METHODS: Patients enrolled in PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) were divided into 3 groups: those with no NC lesions, 1 NC lesion, or ≥2 NC lesions. Time to events for major adverse cardiac events was estimated up to 3 years.

RESULTS: Among 697 patients, 13.3% had no NC lesions, 19.7% had 1 NC lesion, and 67.0% had ≥2 NC lesions. The median diameter stenoses of the NC lesions in the latter 2 groups were 36.7% (interquartile range: 31.0% to 43.4%) and 37.4% (interquartile range: 32.0% to 46.5%), respectively (p = 0.22). At least 1 thin-cap fibroatheroma was present in one-half the patients in each group. At 3 years, the incidence of major adverse cardiac events was 8.5%, 15.2%, and 24.3%, respectively (p = 0.0009). NC lesion-related events occurred in 0%, 5.0%, and 15.9% of patients, respectively (p < 0.0001). Of 105 NC lesion-related clinical events occurring during follow-up, 73 (69.5%) originated from angiographically evident baseline NC lesions (of which 36 had diameter stenosis >50%), while the other 32 arose from normal or near normal segments.

CONCLUSIONS: Residual NC lesions are common after percutaneous coronary intervention for acute coronary syndromes and portend a higher rate of recurrent ischemic events within 3 years, especially when angiographically more severe. Conversely, the absence of NC lesions by angiography is highly predictive of freedom from events not related to the originally treated culprit lesion(s).

PMID: 22421235

Calcium Scoring in Patients with a History of Kawasaki Disease

OBJECTIVES: The goal of this study was to assess coronary artery calcification in patients ≥10 years or age with a history of Kawasaki disease (KD). Patients with a history of KD and coronary artery aneurysms are at risk for late morbidity from coronary artery events. It is unknown whether patients with KD with acutely normal or transiently dilated coronary arteries also have increased risk of late coronary artery complications. Coronary calcium scoring using noncontrast computed tomography is a well-established tool for risk-stratifying patients with atherosclerotic coronary artery disease, but there are limited data on its role in evaluating patients with a history of KD.

METHODS: We performed coronary artery calcium (CAC) volume scoring using a low radiation dose computed tomography protocol on 70 patients (median age 20.0 years) with a remote history of KD (median interval from acute KD to imaging 14.8 years). Forty-four (63%) patients had no history of coronary dilation, 12 (17%) had a history of transient dilation, and 14 (20%) had coronary aneurysms.

RESULTS: All of the patients with normal coronary artery internal diameter during the acute phase of KD and 11 of 12 patients with transient dilation had CAC scores of zero. Coronary calcification was observed in 10 of the 14 patients with coronary aneurysms, with the degree of calcification ranging from mild to severe and occurring years after the patients’ acute KD.

CONCLUSIONS: Coronary calcification was not observed in patients with a history of KD and normal coronary arteries during the acute phase. Therefore, CAC scanning may be a useful tool to screen patients with a remote history of KD or suspected KD and unknown coronary artery status. Coronary calcification, which may be severe, occurs late in patients with coronary aneurysms. The pathophysiology and clinical implications of coronary calcification in patients with aneurysms are currently unknown and warrant further study.

PMID: 22421171

Impact of Statin Therapy on Plaque Characteristics as Assessed by Serial OCT, Grayscale and Integrated Backscatter-IVUS

OBJECTIVES: The purpose of this study was to evaluate the effect of statin treatment on coronary plaque composition and morphology by optical coherence tomography (OCT), grayscale and integrated backscatter (IB) intravascular ultrasound (IVUS) imaging. Although previous studies have demonstrated that statins substantially improve cardiac mortality, their precise effect on the lipid content and fibrous cap thickness of atherosclerotic coronary lesions is less clear. While IVUS lacks the spatial resolution to accurately assess fibrous cap thickness, OCT lacks the penetration of IVUS. We used a combination of OCT, grayscale and IB-IVUS to comprehensively assess the impact of pitavastatin on plaque characteristics.

METHODS: Prospective serial OCT, grayscale and IB-IVUS of nontarget lesions was performed in 42 stable angina patients undergoing elective coronary intervention. Of these, 26 received 4 mg pitavastatin after the baseline study; 16 subjects who refused statin treatment were followed with dietary modification alone. Follow-up imaging was performed after a median interval of 9 months.

RESULTS: Grayscale IVUS revealed that in the statin-treated patients, percent plaque volume index was significantly reduced over time (48.5 ± 10.4%, 42.0 ± 11.1%; p = 0.033), whereas no change was observed in the diet-only patients (48.7 ± 10.4%, 50.4 ± 11.8%; p = NS). IB-IVUS identified significant reductions in the percentage lipid volume index over time (34.9 ± 12.2%, 28.2 ± 7.5%; p = 0.020); no change was observed in the diet-treated group (31.0 ± 10.7%, 33.8 ± 12.4%; p = NS). While OCT demonstrated a significant increase in fibrous cap thickness (140 ± 42 μm, 189 ± 46 μm; p = 0.001), such changes were not observed in the diet-only group (140 ± 35 μm, 142 ± 36 μm; p = NS). Differences in the changes in the percentage lipid volume index (-6.8 ± 8.0% vs. 2.8 ± 9.9%, p = 0.031) and fibrous cap thickness (52 ± 32 μm vs. 2 ± 22 μm, p < 0.001) over time between the pitavastatin and diet groups were highly significant.

CONCLUSIONS: Statin treatment induces favorable plaque morphologic changes with an increase in fibrous cap thickness, and decreases in both percentage plaque and lipid volume indexes.

PMID: 22340823

Low-Flow, Low-Gradient Severe Aortic Stenosis Despite Normal Ejection Fraction Is Associated With Severe Left Ventricular Dysfunction as Assessed by Speckle-Tracking Echocardiography: A Multicenter Study

OBJECTIVES: Low-flow low-gradient (LFLG) is sometimes observed in severe aortic stenosis (AS) despite normal ejection fraction, but its frequency and mechanisms are still debated.  We aimed to describe the characteristics of patients with LFLG AS and assess the presence of longitudinal left ventricular dysfunction in these patients.

METHODS: In a multicenter prospective study, 340 consecutive patients with severe AS and normal ejection fraction were studied.  Longitudinal left ventricular function was assessed by 2D-strain and global afterload by valvulo-arterial impedance.  Patients were classified according to flow and gradient: low flow was defined as a stroke volume index ≤35 mL/m(2), low gradient as a mean gradient ≤40 mm Hg.

RESULTS: Most patients (n=258, 75.9%) presented with high-gradient AS, and 82 patients (24.1%) with low-gradient AS.  Among the latter, 52 (15.3%) presented with normal flow and low gradient and 30 (8.8%) with LFLG.  As compared with normal flow and low gradient, patients with LFLG had more severe AS (aortic valve area=0.7±0.12 cm(2) versus 0.86±0.14 cm(2)), higher valvulo-arterial impedance (5.5±1.1 versus 4±0.8 mm Hg/mL/m(2)), and worse longitudinal left ventricular function (basal longitudinal strain=-11.6±3.4 versus -14.8±3%; P<0.001 for all).

CONCLUSIONS: LFLG AS is observed in 9% of patients with severe AS and normal ejection fraction and is associated with high global afterload and reduced longitudinal systolic function.  Patients with normal-flow low-gradient AS are more frequent and present with less severe AS, normal afterload, and less severe longitudinal dysfunction.  Severe left ventricular longitudinal dysfunction is a new explanation to the concept of LFLG AS.

PMID: 22109983

Deformation Dynamics and Mechanical Properties of the Aortic Annulus by 4-Dimensional Computed Tomography Insights into the Functional Anatomy of the Aortic Valve Complex and Implications for Transcatheter Aortic Valve Therapy

OBJECTIVES: The purpose of this study was to assess deformation dynamics and in vivo mechanical properties of the aortic annulus throughout the cardiac cycle. Understanding dynamic aspects of functional aortic valve anatomy is important for beating-heart transcatheter aortic valve implantation.

METHODS: Thirty-five patients with aortic stenosis and 11 normal subjects underwent 256-slice computed tomography. The aortic annulus plane was reconstructed in 10% increments over the cardiac cycle. For each phase, minimum diameter, ellipticity index, cross-sectional area (CSA), and perimeter (Perim) were measured. In a subset of 10 patients, Young’s elastic module was calculated from the stress-strain relationship of the annulus.

RESULTS: In both subjects with normal and with calcified aortic valves, minimum diameter increased in systole (12.3 ± 7.3% and 9.8 ± 3.4%, respectively; p < 0.001), and ellipticity index decreased (12.7 ± 8.8% and 10.3 ± 2.7%, respectively; p < 0.001). The CSA increased by 11.2 ± 5.4% and 6.2 ± 4.8%, respectively (p < 0.001). Perim increase was negligible in patients with calcified valves (0.56 ± 0.85%; p < 0.001) and small even in normal subjects (2.2 ± 2.2%; p = 0.01). Accordingly, relative percentage differences between maximum and minimum values were significantly smallest for Perim compared with all other parameters. Young’s modulus was calculated as 22.6 ± 9.2 MPa in patients and 13.8 ± 6.4 MPa in normal subjects.

CONCLUSIONS: The aortic annulus, generally elliptic, assumes a more round shape in systole, thus increasing CSA without substantial change in perimeter. Perimeter changes are negligible in patients with calcified valves, because tissue properties allow very little expansion. Aortic annulus perimeter appears therefore ideally suited for accurate sizing in transcatheter aortic valve implantation.

PMID: 22222074

Prognostic Value of Routine Cardiac Magnetic Resonance Assessment of Left Ventricular Ejection Fraction and Myocardial Damage: An International, Multicenter Study

OBJECTIVES: Cardiac magnetic resonance (CMR) is considered the reference standard for assessment of left ventricular ejection fraction (LVEF) and myocardial damage.  However, few studies have evaluated the relationship between CMR findings and patient outcome, and of these, most are small and none multicenter.  We performed an international, multicenter study to assess the prognostic importance of routine CMR in patients with known or suspected heart disease.

METHODS: From 10 centers in 6 countries, consecutive patients undergoing routine CMR assessment of LVEF and myocardial damage by cine and delayed-enhancement imaging (DE-CMR), respectively, were screened for enrollment.  Clinical data, CMR protocol information, and findings were collected at all sites and submitted to the data coordinating center for verification of completeness and analysis.  The primary end point was all-cause mortality.

RESULTS: A total of 1560 patients (age, 59±14 years; 70% men) were enrolled.  Mean LVEF was 45±18%, and 1049 (67%) patients had hyperenhanced tissue (HE) on DE-CMR indicative of damage.  During a median follow-up time of 2.4 years (interquartile range, 1.2, 2.9 years), 176 (11.3%) patients died.  Patients who died were more likely to be older (P<0.0001), have coronary disease (P=0.004), have lower LVEF (P<0.0001), and have more segments with HE (P<0.0001).  In multivariable analysis, age, LVEF, and number of segments with HE were independent predictors of mortality.  Among patients with near-normal LVEF (≥50%), those with above-median HE (>4 segments) had reduced survival compared to patients with below- or at-median HE (P=0.02).

CONCLUSIONS: Both LVEF and amount of myocardial damage as assessed by routine CMR are independent predictors of all-cause mortality.  Even in patients with near-normal LVEF, significant damage identifies a cohort with a high risk for early mortality.

PMID: 21911738

Comparison of Severity of Aortic Regurgitation by Cardiovascular Magnetic Resonance Versus Transthoracic Echocardiography

OBJECTIVES: Transthoracic echocardiography is the current standard for assessing aortic regurgitation (AR).  AR severity can also be evaluated by flow measurement in the ascending aorta using cardiac magnetic resonance (CMR); however, the optimal site for flow measurement and the regurgitant fraction (RF) severity grading criteria that best compares with the transthoracic echocardiographic assessment of AR are not clear.  The present study aimed to determine the optimal site and RF grading criteria for AR severity using phase-contrast flow measurements and CMR.

METHODS: A prospective observational study was performed of 107 consecutive patients who were undergoing CMR of the thoracic aorta.  Using CMR, the AR severity and aortic dimensions were measured at 3 levels in the aorta (the sinotubular junction, mid-ascending aorta, and distal ascending aorta).

RESULTS: The results were compared to the transthoracic echocardiographic grade of AR severity using multiple qualitative and quantitative criteria (grade 0, none; I+, mild; II+, mild to moderate; III+, moderate to severe; and IV+, severe).  The mean RF values were significantly greater at the sinotubular junction than at the distal ascending aorta (13 ± 13.3% vs 9.4 ± 12.6%, respectively; p <0.001).  The RF values that best defined AR severity using phase-contrast CMR were as follows: grade 0 to I+, <8%; grade II+, 8% to 19%; grade III+, 20 to 29%; and grade IV+, 30%) at the sinotubular or mid-ascending aorta.

CONCLUSIONS: In conclusion, the quantitative RF values of AR severity using phase-contrast flow are best assessed in the proximal ascending aorta and differ from recognized quantitative echocardiographic criteria.

PMID: 21784393

Left Ventricular Structural Remodeling in Health and Disease: With Special Emphasis on Volume, Mass, and Geometry

The changes in left ventricular (LV) structure and geometry that evolve after myocardial injury or overload usually involve chamber dilation and/or hypertrophy. Such architectural remodeling can be classified as eccentric or concentric. Consideration of LV volume, mass, and relative wall thickness (or mass/volume) allows classification of LV remodeling that includes virtually all LV remodeling changes that are seen in health and disease. These various architectural changes generally include the development of LV hypertrophy in a pattern that is closely related to the type of injury or overload, and they are accompanied by differences in cardiac function and hemodynamics. Some patterns of remodeling are associated with adverse outcomes whereas others appear to be adaptive and physiologic without adverse consequences. Considering all patients with LV hypertrophy as a homogenous group is inconsistent with our understanding of the various remodeling patterns that are discussed in this review.

PMID: 21996383

Serial Doppler Echocardiography and Tissue Doppler Imaging in the Detection of Elevated Directly Measured Left Atrial Pressure in Ambulant Subjects With Chronic Heart Failure

OBJECTIVES:  Echocardiographic indexes including the ratio of transmitral to annular early diastolic velocities (E/e’) may identify raised invasively measured left ventricular filling pressures when tested in cross-sectional studies in some populations. The accuracy of these indexes when measured sequentially remains untested. We determined the accuracy of Doppler echocardiography and tissue Doppler imaging (TDI) measurements in detecting elevated directly measured left atrial pressure (LAP) in ambulant subjects with stable chronic heart failure.This study sought to determine the accuracy of Doppler echocardiography and TDI measurements in detecting elevated LAP in ambulant subjects with chronic heart failure using directly measured LAP as the reference.

METHODS:  Fifteen patients with New York Heart Association functional class II to III heart failure and a permanently implanted direct LAP monitoring device underwent serial echocardiography. Simultaneous resting mean LAP, Doppler mitral inflow, mitral annular TDI, and pulmonary venous inflow velocities were obtained on each occasion. Receiver-operator characteristic curve analysis was used to compare the accuracy of the Doppler variables to detect an elevated device LAP≥15 and ≥20 mm Hg.

RESULTS: The patients (13 men, mean age: 71 years, mean left ventricular ejection fraction: 32 ± 12%) underwent 60 simultaneous echocardiographic studies and LAP measurements with a median of 4 (1 to 7) studies per patient. Mean LAP was 16.9 (range 5 to 39 mm Hg) at
echocardiography (n = 60). E/e’ had the greatest accuracy for detection of LAP≥15 mm Hg with an area beneath the receiver-operator characteristic curve >0.9. In comparison, area under the curve for mitral E velocity and mitral E/A were 0.77 and 0.76, respectively (p<0.008 vs. E/e’ medial and average).

CONCLUSIONS:  Single and serial measurements of mitral inflow and mitral annular TDI velocities (E/e’) can reliably detect raised directly measured LAP in ambulant subjects with compensated chronic heart failure.

PMID: 21920328

Apical Hypertrophic Cardiomyopathy: Prevalence and Correlates of Apical Outpouching

OBJECITVES: Apical outpouching, including wall motion abnormalities and aneurysms, has been described in apical hypertrophic cardiomyopathy (ApHCM).

METHODS: Between 1976 and 2006, 193 patients with ApHCM (120 men; overall mean age, 61 ± 17 years) were evaluated.

RESULTS: Apical outpouching was found in 29 patients (15%) and in 22 of the 78 patients (28%) imaged with contrast echocardiography. Six patients had apical aneurysms, and 23 patients had hypokinesis with apical dilatation but no wall thinning. Apical outpouching was more common in patients with diastolic gradients out of the apex (P < .001), corrected QT interval prolongation (P < .001), increased apical wall thickness (P = .01), and family histories of sudden cardiac death (P = .03). Sudden cardiac death, resuscitated cardiac arrest, or discharge of an automated internal cardiac defibrillator, or a combination, was observed in 11 patients (6%) during follow-up. Atrial fibrillation (28%), ventricular tachycardia (20%), and stroke (11%) were also relatively common in this study. No difference was observed in overall mortality rate comparing patients with ApHCM with and without apical outpouching. Similarly, no differences were found in the rates of sudden cardiac death, resuscitated cardiac arrest, and discharge of an automated internal cardiac defibrillator. The impact of true aneurysms was not assessed in this study.

CONCLUSIONS: Cardiac complications appear commonly in patients with ApHCM, but they did not seem to be related to apical outpouching in the present analysis.

PMID: 21511435

Mitral and Tricuspid Annular Velocities in Constrictive Pericarditis and Restrictive Cardiomyopathy: Correlation With Pericardial Thickness on Computed Tomography

OBJECTIVES: The aims of this study were to: 1) compare early diastolic mitral annular velocity (E’) of septal annulus (SE’) with E’ of lateral mitral annulus (LE’) and right lateral tricuspid annulus (RE’) in patients with constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM); and 2) assess the relationship between pericardial thickness measured by computed tomography and lateral E’ velocity.The SE’ velocity has been shown to be able to distinguish CP from RCM. However, tissue Doppler parameters of LE’ and RE’ velocities in patients with CP have not been comprehensively analyzed in comparison with SE’. Moreover, the impact of pericardial thickness on the lateral annulus velocity has not been assessed.

METHODS: Thirty-seven patients with CP, 35 patients with RCM, and 70 normal controls were evaluated with echocardiography including SE’, LE’, and RE’. In CP, the maximal pericardial thicknesses on both left and right ventricle were measured by computed tomography.

RESULTS: Mean LE’/SE’ (ratio between mitral LE’ and SE’) was 0.94 ± 0.17 and RE’/SE’ (ratio between tricuspid RE’ and mitral SE’) was 0.81 ± 0.26 in patients with CP, which were lower than those in normal controls (LE’/SE’ 1.36 ± 0.24; RE’/SE’ 1.30 ± 0.32; both p < 0.001) and patients with RCM (LE’/SE’ 1.35 ± 0.31; RE’/SE’ 1.96 ± 0.71; both p < 0.001). There was a significant inverse correlation between right pericardial thickness and RE’ (ρ = -0.489; p = 0.002) and similar trend between left pericardial thickness and LE’ (ρ = -0.284; p = 0.089).

CONCLUSIONS: The ratio between lateral and septal E’ was significantly reduced in patients with CP compared with that in normal control patients and patients with RCM so that the reduced ratios of LE’/SE’ and RE’/SE’ appear to be a useful diagnostic parameter for CP. Moreover, reduced lateral E’ was correlated with the pericardial thickness on their respective sides.

PMID: 21679889

Association Between High-Sensitivity C-Reactive Protein and Coronary Plaque Subtypes Assessed by 64-Slice Coronary Computed Tomography Angiography in an Asymptomatic Population

PMID: 21422167

Troponin T Levels and Infarct Size by SPECT Myocardial Perfusion Imaging

OBJECTIVES: To evaluate the relationship between serial cardiac troponin T (cTnT) levels with infarct size and left ventricular ejection fraction by gated single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in patients with acute myocardial infarction (AMI). Current guidelines recommend the use of cTnT as the biomarker of choice for the diagnosis of AMI. Data relating cTnT to SPECT-MPI in patients with AMI are limited.

METHODS: A subset of patients with their first AMI participating in a community-based cohort of AMI in Olmsted County, Minnesota, were prospectively studied. Serial cTnT levels were evaluated at presentation, <12 h and 1, 2, and 3 days after onset of pain. Peak cTnT was defined as the maximum cTnT value.

RESULTS: A total of 121 patients (age, 61 ± 13 years; 31% women) with AMI underwent gated SPECT-MPI at a median (25th percentile, 75th percentile) of 10 (5, 15) days post-AMI. The type of infarct was non-ST-segment elevation myocardial infarction in 61%, and 13% were anterior in location. The median infarct size was 1% (0%, 11%) and the median gated left ventricular ejection fraction was 54% (47%, 60%). Fifty-nine patients (49% of the population) had no measurable infarction by SPECT-MPI. Independent predictors of measurable SPECT-MPI infarct size included cTnT at days 1, 2, and 3 and peak cTnT, but not at presentation or <12 h. In receiver-operator characteristic analysis, the area under the curve was highest at day 3. Receiver-operator characteristic analysis demonstrated a cutoff of 1.5 ng/ml for peak cTnT for the detection of measurable infarct size.

CONCLUSIONS: In a community-based cohort of patients with their first AMI, independent predictors of measurable SPECT-MPI infarct size included cTnT at days 1, 2, and 3 and peak cTnT. In contrast, cTnT level at presentation and <12 h was not an independent predictor of myocardial infarction size as assessed by SPECT-MPI. Receiver-operator characteristic analysis demonstrated a cutoff value peak cTnT of 1.5 ng/ml for the detection of measurable infarct.

PMID: 21565741

Diastolic Relaxation and Compliance Reserve During Dynamic Exercise in Heart Failure With Preserved Ejection Fraction

OBJECTIVES: Recent studies have examined haemodynamic changes with stressors such as isometric handgrip and rapid atrial pacing in heart failure with preserved ejection fraction (HFpEF), but little is known regarding left ventricular (LV) pressure-volume responses during dynamic exercise.  The objective is to assess LV haemodynamic responses to dynamic exercise in patients with HFpEF.

METHODS:  Twenty subjects with normal ejection fraction (EF) and exertional dyspnoea underwent invasive haemodynamic assessment during dynamic exercise to evaluate suspected HFpEF.

RESULTS:  LV end-diastolic pressure was elevated at rest (>15&emsp14; mmHg, n=18) and with exercise (≥20&emsp14;mmHg, n=20) in all subjects, consistent with HFpEF. Heart rate (HR), blood pressure, arterial elastance and cardiac output increased with exercise (all p<0.001).  Minimal and mean LV diastolic pressures increased by 43-56% with exercise (both p<0.0001), despite a trend towards a reduction in LV end-diastolic volume (p=0.08).  Diastolic filling time was abbreviated with increases in HR and the proportion of diastole that elapsed prior to estimated complete relaxation increased (p<0.0001), suggesting inadequate relaxation reserve relative to the shortening of diastole.  LV diastolic chamber elastance acutely increased 50% during exercise (p=0.0003).  Exercise increases in LV filling pressures correlated with changes in diastolic relaxation rates, chamber stiffness and arterial afterload but were not related to alterations in preload volume, HR or cardiac output.

CONCLUSIONS:  In patients with newly diagnosed HFpEF, LV filling pressures increase during dynamic exercise in association with inadequate enhancement of relaxation and acute increases in LV chamber stiffness.  Therapies that enhance diastolic reserve function may improve symptoms of exertional intolerance in patients with hypertensive heart disease and early HFpEF.

PMID: 21586744