Changes In Left Ventricular Stroke Volume Research Articles

Effect of patisiran on stroke volume in hereditary transthyretin-mediated amyloidosis: insights from pressure-volume analysis of the APOLLO study.

Transthyretin-mediated (ATTR) amyloidosis is caused by deposition of transthyretin protein fibrils in the heart, nerves, and other organs. Patisiran, an RNA interference therapeutic that inhibits hepatic synthesis of transthyretin, was approved for the treatment of hereditary ATTR amyloidosis with polyneuropathy based on the phase 3 APOLLO study. We use left ventricular (LV) stroke volume (SV) to quantify LV function overtime and non-invasive pressure-volume techniques to delineate the effects of patisiran on LV mechanics in the pre-specified cardiac subpopulation of the APOLLO study. Left ventricular SV was assessed by transthoracic echocardiography at baseline, and after 9 and 18 months of therapy. To determine the mechanisms underlying changes in LV SV, non-invasive pressure-volume parameters, including the end-systolic and end-diastolic pressure-volume relationship, were derived using single beat techniques. At baseline, the mean SV was 51 ± 14ml. At 9months, the least-squares mean change in SV was -0.3 ± 1.2ml for patisiran and -5.4 ± 1.9ml for placebo (p= 0.021). At 18 months, the least-squares mean change in SV was -1.7 ± 1.3ml for patisiran and - 8.1 ± 2.3ml for placebo (p= 0.016). Decline in LV SV was driven by diminished LV capacitance in placebo relative to patisiran. Patisiran may delay progression of LV chamber dysfunction starting at 9months of therapy. These data elucidate the mechanisms by which transthyretin-reducing therapies modulate progression of cardiac disease and need to be confirmed in ongoing phase 3 trials.

Tafamidis Reduces The Decline In Longitudinal Strain And Stroke Volume In Patients With Transthyretin Amyloid Cardiomyopathy

<h3>Introduction</h3> Left ventricular (LV) longitudinal strain and stroke volume are significant predictors of mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis significantly reduced mortality and CV-related hospitalizations. Further analysis of changes in echocardiographic measures in ATTR-ACT may provide additional insight into the efficacy of tafamidis. <h3>Hypothesis</h3> Treatment with tafamidis significantly reduces the worsening of echocardiographic variables including LV longitudinal strain and stroke volume in ATTR-CM patients. <h3>Methods</h3> In ATTR-ACT, ATTR-CM patients (variant or wild-type) were treated with tafamidis 80 mg (n=176) or placebo (n=177) for 30 months. Echocardiography was conducted at enrollment, and at Months 6, 18 and 30, using a standardized protocol and analyzed by an independent central laboratory. We compared changes in LV stroke volume (SV), global longitudinal strain (GLS) and mitral inflow E wave/annular diastolic early (e') wave (E/e') in patients treated with tafamidis 80 mg (the approved dose) vs placebo. <h3>Results</h3> Baseline mean (SD) SV (mL), GLS (%) and septal and lateral E/e' were similar in the tafamidis and placebo groups (<b>Table</b>). Each measure worsened over the duration of the trial, as shown by least-squares (LS) mean (SE) change from baseline at Month 30 for each group (<b>Table</b>). This decline was more pronounced in placebo-treated patients, with a significant reduction in LS mean difference (95% CI) with tafamidis vs placebo for each measure (<i>P</i><0.05 for all). Decline in SV and GLS was apparent from Month 6 in all patients; difference between tafamidis and placebo groups was apparent from Month 18. Decline in E/e' (indicative of elevated LV filling pressures) was apparent from Month 6 with placebo but only minimally changed with tafamidis at each time point; difference between tafamidis and placebo was apparent from Month 6. <h3>Conclusions</h3> LV longitudinal strain and stroke volume are significant predictors of mortality in ATTR-CM patients. Treatment with tafamidis significantly reduced worsening progression of LV systolic (GLS, SV) and diastolic function (E/e') over 30 months in ATTR-CM patients. These echocardiographic data provide additional insight into the efficacy of tafamidis.

HIIT Improves Left Ventricular Exercise Response in Adults with Type 2 Diabetes.

This study aimed to determine whether 3 months of high-intensity interval training (HIIT) improves left ventricular function during exercise in adults with type 2 diabetes. Participants performed a V˙O2peak test and received a DXA scan and total blood volume measurement at baseline. Left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular stroke volume (LVSV) were then measured at rest and during low- and moderate-intensity semirecumbent exercise in adults with type 2 diabetes before and after 3 months of HIIT (n = 11) or no training (control) (n = 5). The effects of HIIT were determined using repeated-measures ANOVA. HIIT increased V˙O2peak by approximately 15% (P < 0.002) but did not change body composition or total blood volume. LVESV decreased and LVEDV and LVSV increased from rest to moderate-intensity exercise in both groups at baseline (all P < 0.01). Three months of HIIT increased LVEDV (P = 0.008) and LVSV (P = 0.02) at all conditions, but there was no difference in controls (all P > 0.05). HIIT augmented the reduction in LVESV from rest to moderate-intensity exercise (P < 0.04), but LVESV was unchanged in controls. Increased LVEDV explained 51% of the change in LVSV after HIIT intervention. Mitral inflow parameters and mitral annular velocities were unaffected by HIIT (all P > 0.05). HIIT training increased the LVSV response to exercise in adults with type 2 diabetes. These data suggest that HIIT can improve LV filling and emptying during exercise and reverse early cardiac consequences of type 2 diabetes.

Cardiovascular Mechanisms of Extravascular Lung Water Accumulation in Divers

This study assessed the relation between altered cardiac function and the development of interstitial pulmonary edema in scuba divers. Fifteen healthy men performed a 30-minute scuba dive in open sea. They were instructed to fin for 30minutes and were wearing wet suits. Before and immediately after immersion, cardiac indexes and extravascular lung water were measured using echocardiography and lung ultrasound, respectively. The mean ultrasound lung comet score increased from 0 to 4.6 ± 3.4. The diameter of the inferior caval vein increased by 47 ± 5.2%, systolic pulmonary artery pressure by 105 ± 8.6%, left atrial volume by 18.0 ± 3.3%, and left ventricle end-diastolic volume by 10 ± 2.4% suggesting that both right and left ventricular (LV) filling pressures were elevated. Doppler studies showed an increased mitral E peak (+2.5 ± 0.3%) and E/A ratio (+22.5 ± 3.4%) with a decreased mitral A peak (-16.4 ± 2.7%), E peak deceleration time (-14.5 ± 2.4%) consistent with rapid early LV filling but without a change in LV stroke volume. There was an increase in right/left ventricle diameter ratio (+33.6 ± 4.8%) suggesting a relative increase in right-sided heart output compared with the left. Furthermore, the lung comet score correlated significantly with inferior caval vein diameter, systolic pulmonary artery pressure, right/left ventricle diameter ratio, and E-wave deceleration time. In conclusion, the altered right/left heart stroke volume balance could play an essential role in the development of immersion pulmonary edema. Our findings have important implications for the pathogenesis of cardiogenic pulmonary edema.

Influence of left ventricular lead position relative to scar location on response to cardiac resynchronization therapy: a model study.

It is unclear how the position of the left ventricular (LV) lead relative to a scar affects the haemodynamic response in patients with dyssynchronous heart failure receiving cardiac resynchronization therapy. We investigated this complex interaction using a computational model. The CircAdapt computational cardiovascular system model was used to simulate heart failure with left bundle branch block (LBBB). Myocardial scar was induced in four different regions of the LV free wall (LVFW). We then simulated biventricular pacing (BVP) in each heart, in which LV lead position was varied. The LV lead position leading to maximal acute change in LV stroke volume (SV) was defined as optimal lead position. In LBBB without scar, SV increase was maximal when pacing the LVFW region most distant from the septum. With a scar adjacent to the septum, maximal response was achieved when pacing remote from both the septum and the scar. When the scar was located further from the septum, the BVP-induced increase of SV was small. For all hearts, pacing from the optimal LV lead position resulted in the most homogeneous distribution of local ventricular myofibre work and the largest increase in summed left and right ventricular pump work. These computer simulations suggest that, in hearts with LBBB and scar, the optimal LV lead position is a compromise between a position distant from the scar and from the septum. In infarcted hearts, the best haemodynamic effect is achieved when electromechanical resynchronization of the remaining viable myocardium is most effective.

Neonatal cardiac dysfunction in intrauterine growth restriction

The early postnatal cardiovascular consequences of intrauterine growth restriction (IUGR) have not been completely elucidated. This study aimed to evaluate the effect of IUGR on neonatal myocardial function and cardiovascular adaptation to extrauterine life. Conventional and tissue Doppler echocardiographic parameters were compared on the second and fifth postnatal day between 30 IUGR and 30 appropriate-for-gestational age (AGA) neonates. IUGR neonates presented relative interventricular septum (IVS) hypertrophy (IVS to left ventricular (LV) posterior wall diastolic ratio: median IUGR-AGA difference of 0.05 (interquartile range: 0.04-0.06); P = 0.020), relative LV dilatation (wall thickness to end-diastolic LV dimension difference of 0.12 (0.06-0.16); P = 0.012), and increased left myocardial performance index (MPI difference of 0.19 (0.05-0.28); P = 0.012). Repeated measurements ANOVA revealed a different pattern of change in LV stroke volume (LVSV; P < 0.001), LV cardiac output (LVCO; P < 0.001), MPI (P < 0.001), and heart rate (HR; P = 0.025) between AGA and IUGR infants. From the second to the fifth postnatal day, AGA neonates presented a decrease in MPI and HR with an increase in LVSV and LVCO. IUGR neonates failed to achieve similar changes in MPI, HR, and LVSV, whereas their LVCO decreased. IUGR neonates present changes in cardiac morphology and subclinical myocardial dysfunction, which may result in an altered pattern of cardiovascular adaptation to extrauterine life.

Hemodynamic Impact and Outcome of Permanent Pacemaker Implantation Following Transcatheter Aortic Valve Implantation

Transcatheter aortic valve implantation (TAVI) frequently requires postprocedural permanent pacemaker (PPM) implantation. We evaluated clinical and hemodynamic impact of PPM after TAVI. Clinical and echocardiographic data were retrospectively analyzed in 230 consecutive patients who underwent TAVI and echocardiography at baseline and after 6 months. Echocardiographic parameters included left ventricular ejection fraction (LVEF), left ventricular (LV) stroke volume, early mitral velocity/annulus velocity ratio (E/e'), right ventricular index of myocardial performance, systolic pulmonary artery pressure (SPAP), and aortic, mitral, and tricuspid regurgitation grades. Clinical outcomes included 2-year survival and cardiovascular and PPM-related event-free survival. The Medtronic CoreValve and Edwards Sapien prosthesis were used in 201 and 29 patients, respectively. PPM was required in 58 patients (25.4%). Two-year and event-free survival rates were similar between patients with and without PPM. At 6 months, patients with PPM demonstrated attenuated improvement in LVEF (-0.9 ± 8.7% vs 2.3 ± 10.8%, respectively, p = 0.03) and LV stroke volume (-2 ± 16 vs 4 ± 10 ml/m(2), respectively, p = 0.015), a trend toward smaller reduction in systolic pulmonary artery pressure (-1 ± 12 vs -6 ± 10 mm Hg, respectively, p = 0.09), and deterioration of right ventricular index of myocardial performance (-3 ± 17% vs 5 ± 26%, respectively, p = 0.05). The differences in post-TAVI aortic, mitral, and tricuspid regurgitation grades were insignificant. In conclusion, PPM implantation after TAVI is associated with reduced LVEF and impaired LV unloading. However, this unfavorable hemodynamic response does not affect the 2-year clinical outcome. The maintenance of clinical benefit appears to be driven by TAVI-related recovery of LV and right ventricular performance that mitigates unfavorable impact of PPM.

SKA‐31, a positive modulator of SKCa and IKCa channels, increases systemic conductance and lowers arrterial pressure in an anesthetized pig model

SKA‐31 regulates microvascular tone, tissue perfusion and blood pressure by acting on endothelial SKCa and IKCa channels. In this study, we have examined the hemodynamic effects of SKA‐31 in comparison to the established vasodilator sodium nitroprusside (SNP) in anesthetized domestic pigs. We measured left ventricular (LV), aortic and inferior vena cava (IVC) pressures and monitored levels of blood flow in the ascending aorta, right carotid, left anterior descending coronary and left renal arteries during acute intravenous infusions of SKA‐31 (0.1 to 5 mg/kg), followed by a single dose of SNP (5 μg/kg). SKA‐31 dose‐dependently and reversibly decreased mean aortic pressure (mPAO) to a level comparable to that produced by SNP (−23±3 vs. −28±4 mmHg). Mean IVC pressure did not change. Both SKA‐31 (1 to 5 mg/kg doses) and SNP increased systemic conductance, along with coronary and carotid artery conductances; renal conductance did not change. There was no change in LV stroke volume (SV) for any infusion, and heart rate was not altered following SKA‐31 administration (132±14 vs. 128±13 bpm). With no change in SV, the significant decrease in LV stroke work (SW) observed with either SKA‐31 or SNP was largely attributed to decreased mPAO. In summary, SKA‐31 significantly decreased mPAO by increasing systemic conductance, and did not appear to reduce cardiac contractility. Supported by the CIHR (JVT and APB) and the NIH (HW).

Case Scenario

Case Scenario

LV Lead Repositioning to Apico-Lateral Position in Non Responders to Resynchronization Therapy Improves Patients Acutely and in Long Term Follow Up

Background: Up to 35% of patients with dyssynchrony do not respond to cardiac resynchronization therapy (CRT). This may result from suboptimal placement of the left ventricular (LV) pacing lead. Currently there is no consensus on the best parameter for the LV lead optimization or the optimal site for LV pacing. Methods: 27 patients, 13 with ischemic cardiomyopathy (ICM) and 14 with non-ischemic cardiomyopathy (NICM), who did not respond to CRT within twelve months, were studied. 19/27 patients had initial LV lead placement in the anterolateral and 8/27 in the lateral-basal segment of the LV. A new LV lead was placed in multiple sites in the coronary venous system. Acute measurements were performed with the conductance catheter to select the new LV pacing site. Change in LV stroke volume and dP/dtmax were used as a guide to optimal lead position, After implantation patients were followed clinically at 1, 3, 6 and 12 months. Echocardiography, the Minnesota Living with Heart Failure Questionnaire, and 6 min hall walk tests were completed at the baseline and 6 month intervals. Results: During acute measurements the biggest increase in stroke volume was seen in the apico lateral segment of the LV. The new apico lateral LV lead position significantly increased stroke volume (+27%, P =.01), stroke work (+45%, P =.04) reduced end-systolic volume (-5%, P =.04) and did not significantly change dP/dtmax (+5%, P =.2) when compared to the old LV lead position in all 27 patients. Long term follow up demonstrated that the acute increase in the LV stroke volume resulted in significantly better response to therapy. After 6 months all patients showed improvement in quality of life and the 6 minute hall walk test, NICM patients had significant increase in EF (+10%, P=0.05) and 12/14 decreased ES and ED volume >15%. ICM patients had worse results EF (+2%, P=0.1) and ES and ED volumes decreased in 7/13. At 12 months 4/13 patients with ICM and 2/14 with NICM died. Conclusions: In patients who are non-responders, repositioning or adding LV lead to the original CRT system with use of hemodynamic guidance significantly improved response. Mechanism of improvement was related to the increase in LV stroke volume, not the change dP/dt max. The optimal LV pacing site was lateral towards the apex in all patients. Despite the improvements the mortality in the ICM group after 12 months was high. Background: Up to 35% of patients with dyssynchrony do not respond to cardiac resynchronization therapy (CRT). This may result from suboptimal placement of the left ventricular (LV) pacing lead. Currently there is no consensus on the best parameter for the LV lead optimization or the optimal site for LV pacing. Methods: 27 patients, 13 with ischemic cardiomyopathy (ICM) and 14 with non-ischemic cardiomyopathy (NICM), who did not respond to CRT within twelve months, were studied. 19/27 patients had initial LV lead placement in the anterolateral and 8/27 in the lateral-basal segment of the LV. A new LV lead was placed in multiple sites in the coronary venous system. Acute measurements were performed with the conductance catheter to select the new LV pacing site. Change in LV stroke volume and dP/dtmax were used as a guide to optimal lead position, After implantation patients were followed clinically at 1, 3, 6 and 12 months. Echocardiography, the Minnesota Living with Heart Failure Questionnaire, and 6 min hall walk tests were completed at the baseline and 6 month intervals. Results: During acute measurements the biggest increase in stroke volume was seen in the apico lateral segment of the LV. The new apico lateral LV lead position significantly increased stroke volume (+27%, P =.01), stroke work (+45%, P =.04) reduced end-systolic volume (-5%, P =.04) and did not significantly change dP/dtmax (+5%, P =.2) when compared to the old LV lead position in all 27 patients. Long term follow up demonstrated that the acute increase in the LV stroke volume resulted in significantly better response to therapy. After 6 months all patients showed improvement in quality of life and the 6 minute hall walk test, NICM patients had significant increase in EF (+10%, P=0.05) and 12/14 decreased ES and ED volume >15%. ICM patients had worse results EF (+2%, P=0.1) and ES and ED volumes decreased in 7/13. At 12 months 4/13 patients with ICM and 2/14 with NICM died. Conclusions: In patients who are non-responders, repositioning or adding LV lead to the original CRT system with use of hemodynamic guidance significantly improved response. Mechanism of improvement was related to the increase in LV stroke volume, not the change dP/dt max. The optimal LV pacing site was lateral towards the apex in all patients. Despite the improvements the mortality in the ICM group after 12 months was high.

Determination of left ventricular volume changes by intracardiac conductance using a biventricular electrode configuration

The feasibility of determining left ventricular (LV) volume changes by LV conductance measurements with an implantable device was investigated in an animal model. The haemodynamic state of six mongrel dogs was altered by overpacing with rates up to 140 bpm and by isoprenaline infusion with dosages up to 0.2 microg/kg/min. The LV conductance, aortic blood flow, and LV and aortic pressure were recorded. Conductance measurements were carried out using the two electrodes of a bipolar right ventricular pacing lead for current injection and two epicardial leads screwed into the mid-lateral LV wall for measuring the resulting voltage. Stroke conductance (SY) was correlated with the LV stroke volume (LVSV), which was computed from the aortic flow. The LVSV rose to 188+/-14% with increasing isoprenaline dosage. A strong correlation between the LV conductance SY and the LVSV was found (mean r=0.97). The LVSV decreased to 68+/-8% with an increasing pacing rate. Again, a strong correlation between SY and LVSV was found (mean r=0.89). This animal study confirms the feasibility of assessing changes in LVSV by determining the LV intracardiac conductance. This creates the possibility of continuous haemodynamic monitoring with implantable devices.

Cyclic changes in arterial pressure during mechanical ventilation.

For a given level of arterial distensibility, the amplitude of the arterial pulse is directly related to the left ventricular (LV) stroke volume. Thus, rapid changes in arterial pulse pressure, the difference between systolic and diastolic pressures, essentially reflect changes in LV stroke volume.

Using heart-lung interactions to assess fluid responsiveness during mechanical ventilation

According to the Frank-Starling relationship, a patient is a 'responder' to volume expansion only if both ventricles are preload dependent. Mechanical ventilation induces cyclic changes in left ventricular (LV) stroke volume, which are mainly related to the expiratory decrease in LV preload due to the inspiratory decrease in right ventricular (RV) filling and ejection. In the present review, we detail the mechanisms by which mechanical ventilation should result in greater cyclic changes in LV stroke volume when both ventricles are 'preload dependent'. We also address recent clinical data demonstrating that respiratory changes in arterial pulse (or systolic) pressure and in Doppler aortic velocity (as surrogates of respiratory changes in LV stroke volume) can be used to detect biventricular preload dependence, and hence fluid responsiveness in critically ill patients.

On-line estimation of stroke volume by means of echocardiographic automated border detection in the canine left ventricle

Echocardiographic automated border detection (ABD) is a new on-line technique that can determine the interface between blood and myocardial tissue and calculate left ventricular (LV) cavity area in real time. The objective of this study was to determine whether ABD measurements of the LV cavity area could be used to estimate LV stroke volume at basal conditions and during large changes in LV stroke volume induced by inferior vena caval occlusions in an open-chest canine model. Seven dogs had LV stroke volume measured by electromagnetic flow from the ascending aorta with epicardial recordings of ABD echocardiographic area at the midventricular short-axis level. Simultaneous beats of stroke volume were recorded along with ABD echo area during baseline apnea and during IVC occlusions. Neither ABD echo stroke area nor stroke volume varied significantly during apnea baseline. Changes in stroke area were closely correlated with changes in stroke volume for 540 matched beats from 24 IVC occlusions: R = 0.93, standard error of the estimate = 5%, y = 0.92 x + 0.4 ( p < 0.001). Echocardiographic ABD appears to be a promising new on-line method of determining rapid alterations in LV stroke volume; it also has potential applications to multiple investigational and clinical settings.

Longitudinal trends in left ventricular cardiac output in healthy infants in the first year of life.

We studied left ventricular (LV) cardiac output as estimated by ascending aorta blood flow (QAo) longitudinally in 31 healthy infants from birth through the first year of life using noninvasive pulsed Doppler ultrasound technique. The temporal mean ascending aortic blood flow velocity (VAo) was measured with a 5-MHz pulsed Doppler velocimeter and on line integration system. Ascending aortic cross-sectional area (AAo) was determined using M-mode echography. Ascending aortic blood flow was calculated as QAo = VAo X AAo and was corrected to body weight (BW) in kilograms or body surface area (BSA) in meters squared. Mean ascending aortic flow velocity (VAo) remained relatively constant over the first year, averaging 20.5 +/- 3.4 cm/sec (+/- SD). Changes in AAo over time correlated strongly with changes in BW or BSA (r = 0.99). Therefore, changes in QAo correlated strongly with changes in AAo, BW, and BSA (r = 0.99). LV cardiac output corrected for body weight or BSA remained relatively constant throughout the first year, mean values ranging from 180-226 ml/min/kg or 3.06-3.76 L/min/m2 and averaging 204 +/- 45 ml/min/kg or 3.48 +/- 0.74 L/min/m2. A similar strong correlation was seen between serial changes in LV stroke volume and changes in BW or BSA (r = 0.99).

228 LONGITUDINAL TRENDS IN LEFT VENTRICULAR CARDIAC OUTPUT IN HEALTHY INFANTS OVER THE FIRST YEAR OF LIFE

We studied left ventricular (LV) cardiac output longitudinally in 16 healthy infants from birth through the first year of life using noninvasive pulsed Doppler ultrasound technique. Ascending aorta blood flow velocity (VAo) was measured with a 5 mHz pulsed Doppler velocimeter. Ascending aortic cross sectional area (AAo) was determined using M-mode echography. Ascending aortic blood flow was calculated as QAo = VAo × AAo and was corrected to body weight (BW) in kilograms or body surface area (BSA) in meters squared. Peak systolic aortic flow velocity averaged 53±2 cm/sec (±SD) over the one year time period. Mean ascending aortic flow velocity (VAo) remained relatively constant over the first year, averaging 20.5±.8cm/sec. Changes in AAo over time correlated with changes in BW and BSA (r = .99) Therefore LV output corrected for body weight or BSA remained relatively constant throughout the first year, ranging from 178-227ml/min/kg or 3.1 - 3.7 L/min/m2 and averaging 204±/15ml/min/kg or 3.5±.2 L/min/m2. A similar strong correlation was seen between serial changes in LV stroke volume and changes in BW or BSA (r = .99). Unlike some other animal species, LV output with respect to BW or BSA changes little in humans over the first year of life.

Afterload mismatch and preload reserve in chronic aortic regurgitation.

SUMMARY We examined the interrelationship of afterload, preload and left ventricular (LV) performance at two levels of systolic loading in 20 patients with chronic aortic regurgitation to determine if the concept of afterload mismatch and preload reserve can be applied to this clinical entity. We identified two groups of patients at different stages in the natural history of volume overload. Patients in group I had moderate LV enlargement (LV end-diastolic volume 150 ml/m2). Both groups had sufficient eccentric hypertrophy, measured by LV mass, to keep afterload as measured by mean systolic LV wall stress only slightly above normal; LV mean systolic wall stress was similar in each group. Patients in group 2 had a lower LVejection fraction and velocity of circumferential fiber shortening than those in group 1 at a similar lower level of afterload. At a similar higher level of afterload, which increased end-diastolic volume from 134 4 to 157 ± 6ml/m2 in group 1 and from 191 ± 9 to 218 13 ml/m2 in group 2 (average increase 18% vs 14%, NS), patients in group 1 maintained their ejection fraction and forward stroke volume and had a significant increase in total LV stroke volume, whereas patients in group 2 had a decrease in ejection fraction and in forward stroke volume and no significant change in LV stroke volume. The velocity of circumferential fiber shortening decreased in both groups in response to increased afterload. These data indicate that patients with moderate LV dilatation due to aortic regurgitation and sufficient hypertrophy to normalize afterload have a preload reserve that permits normal LV performance during a basal state as well as during acute increases in afterload. Patients with severe LV dilatation, however, despite sufficient hypertrophy to normalize afterload, have afterload mismatch due to a depressed inotropic state, and have exhausted preload reserve such that acute increases in afterload worsen the afterload mismatch and cause further deterioration of LV performance. The velocity of circumferential fiber shortening appears to be a less useful indicator of afterload mismatch than other ejection-phase indexes of contractility. Thus, the concept of afterload mismatch and preload reserve describes the natural history of hemodynamic alterations in chronic aortic regurgitation.