Left Ventricular Contractile Response Research Articles

Left ventricular contractile reserve as a determinant of adverse clinical outcomes: a systematic review.

An abnormal left ventricular contractile reserve is often seen in patients undergoing stress echocardiogram and may indicate the presence of obstructive coronary artery disease. The techniques and indexes used to identify abnormal left ventricular contractile response and its prognostic value in the absence of known causes has not been well studied. To describe the characteristics and clinical outcomes associated with an abnormal left ventricular contractile response, we performed a systematic review that identified 27 eligible studies. A diverse range of indices were utilised to measure left ventricular contractile reserve, most commonly Δleft ventricular ejection fraction in 11 studies. Dobutamine stress echocardiogram was the most commonly performed modality (19 studies) followed by exercise stress echocardiogram (4 studies), dipyridamole stress echocardiogram (2 studies), invasive hemodynamic measurement (1 study) and dobutamine stress magnetic resonance imaging (1 study). All but one study demonstrated a significant association between the absence of left ventricular contractile reserve and increased rate of cardiovascular events, cardiac death and all-cause mortality.

Reversible exercise-induced left ventricular dysfunction in symptomatic patients with previous Takotsubo syndrome: insights from stress echocardiography.

Takotsubo syndrome (TTS) is usually associated with rapid and spontaneous recovery of left ventricular (LV) function. However, a proportion of patients may have persistent symptoms. This study aimed to determine the haemodynamic and LV contractile responses to exercise in these patients. Thirty symptomatic TTS patients referred for exercise echocardiography, a median of 15 months following the index TTS episode, were matched with 30 controls with normal exercise echocardiography. Beta-blockers were withheld prior to the test. LV volumes, ejection fraction (EF) and wall motion score index (WMSI), were measured at rest and stress. The TTS cohort were Caucasian women with mean age of 64.6 ± 7.4 years and similar coronary risk factor profile and EF to controls. Resting systolic blood pressure (SBP), LV end-diastolic volume, wall stress, and right ventricular fractional area change were higher in TTS patients compared with controls. Stress echo data showed similar exercise time, peak heart rate, and peak SBP in TTS patients vs. controls, but TTS patients had higher LV volumes, lower exercise LVEF (70 ± 10% vs. 78 ± 7%; P = 0.001), ΔLVEF (4 ± 8% vs. 12 ± 5%; P < 0.001), and WMSI (1.4 ± 0.4 vs. 1 ± 0; P < 0.001) compared with controls. Twenty TTS patients had clear exercise-induced wall motion abnormalities, mainly involving the apex or more globally, with a mean ΔLVEF of 1% compared with 12% in controls. Among the other 10 TTS patients, the ΔLVEF was 10%. Symptomatic patients with previous TTS have a blunted contractile response to exercise. The therapeutic and prognostic implications of these findings need further investigation.

P1497Reversible exercise-induced left ventricular dysfunction in symptomatic patients with previous Takotsubo syndrome - Insights from exercise echocardiography

Abstract Introduction Takotsubo syndrome (TTS) is an acute heart failure syndrome usually associated with rapid and spontaneous recovery of left ventricular (LV) function. However, approximately 10% of patients have persistent symptoms and seek further medical advice. Purpose To determine the cardiovascular haemodynamic and LV contractile response to exercise in these TTS survivors with ongoing symptoms. Methods This was a case-control study of 20 symptomatic patients with previous TTS referred for treadmill exercise echocardiography (EE), and 20 age-, sex- and ethnicity-matched control subjects with normal treadmill EE. Among the TTS group, EE was performed at a median of 8 months (mean 17±21 months) following the index event. Demographic characteristics, resting and EE data were collected. LV ejection fraction (EF) was measured at rest and peak stress. Global longitudinal and circumferential strain (GLS, GCS) were measured at rest. Results All 20 TTS patients were Caucasian postmenopausal females (mean age 63.5±6.6 years). There were no significant differences in body mass index (BMI), resting heart rate (HR) and the prevalence of cardiovascular risk factors compared to controls. Resting systolic and diastolic blood pressure (SBP, DBP) were higher in TTS patients (144±17 mmHg versus 128±18 mmHg, and 81±10 mmHg versus 74±9 mmHg, respectively). A comparative analysis of the resting and stress echo data is given in Table 1. The stress echo data showed similar exercise time and peak HR, but higher peak SBP in TTS patients. TTS patients had blunted contractile response to exercise with lower peak LVEF, ΔLVEF (exercise minus resting EF) and peak wall motion score index (WMSI) compared to controls. Among the 20 TTS patients, 12 had exercise-induced wall motion abnormalities: 6 involved the apical segments and 6 developed global dysfunction. In these 12 patients, the mean ΔLVEF was reduced (4%). In the other 8 patients, the ΔLVEF was 16% and pooled the TTS cohort had blunted contractile response with exercise compared to controls (ΔLVEF 8% vs. 19% in the control group, p=0.001). Table 1 Conclusions Our study shows that symptomatic patients with previous TTS have a blunted contractile response to exercise manifest as reversible apical or global LV dysfunction. These findings might indicate the need for treatment. Further systematic investigation of the therapeutic and prognostic implications of this reversible exercise-induced myocardial dysfunction is needed.

Usefulness of myocardial work measurement in the assessment of left ventricular systolic reserve response to spironolactone in heart failure with preserved ejection fraction.

Improvement in left ventricular (LV) systolic reserve, including exertional increase in global longitudinal strain (GLS), may contribute to the clinical benefit from therapeutic interventions in heart failure with preserved ejection fraction (HFpEF). However, GLS is an afterload-dependent parameter, and its measurements may not adequately reflect myocardial contractility recruitment with exercise. The estimation of myocardial work (MW) allows correction of GLS for changing afterload. We sought to investigate the associations of GLS and MW parameters with the response of exercise capacity to spironolactone in HFpEF. We analysed 114 patients (67 ± 8 years) participating in the STRUCTURE study (57 randomized to spironolactone and 57 to placebo). Resting and immediately post-exercise echocardiograms were performed at baseline and at 6-month follow-up. The following indices of MW were assessed: global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency. The amelioration of exercise intolerance at follow-up in the spironolactone group was accompanied by a significant improvement in exertional increase in GCW (P = 0.002) but not in GLS and other MW parameters. Increase in exercise capacity at 6 months was independently correlated with change in exertional increase in GCW from baseline to follow-up (β = 0.24; P = 0.009) but not with GLS (P = 0.14); however, no significant interaction with the use of spironolactone on peak VO2 was found (P = 0.97). GCW as a measure of LV contractile response to exertion is a better determinant of exercise capacity in HFpEF than GLS. Improvement in functional capacity during follow-up is associated with improvement in exertional increment of GCW.

Stress echocardiography in the assessment of native valve disease

### Learning objectives Stress echocardiography is an established technique for the detection of coronary artery disease, but the echocardiographic assessment of valve disease has conventionally been performed under static conditions....

Cardiovascular Outcomes in Patients with Abnormal Global Left Ventricular Contractile Response on Exercise Stress Echocardiogram

Cardiovascular Outcomes in Patients with Abnormal Global Left Ventricular Contractile Response on Exercise Stress Echocardiogram

P5620Predictors of the absence of obstructive coronary artery disease in patients with an abnormal global left ventricular contractile response to exercise

P5620Predictors of the absence of obstructive coronary artery disease in patients with an abnormal global left ventricular contractile response to exercise

Is exercise stress echocardiography useful in patients with suspected obstructive coronary artery disease who have resting left bundle branch block?

Current guidelines support exercise stress echocardiography (ESE) for evaluation of suspected obstructive coronary artery disease (OCAD) in ambulant patients with left bundle branch block (LBBB). Data regarding the diagnostic utility of ESE in patients with LBBB are limited. We hypothesized that the diagnostic performance of ESE for the assessment of suspected OCAD is reduced in the context of LBBB. We studied 191 consecutive patients with resting LBBB undergoing ESE for the investigation of suspected OCAD between 2008 and 2015 at our center. The studies were categorized as inconclusive, normal, or abnormal. Patients with an abnormal response were subcategorized as regional ischemic response or globally abnormal. Eighty-two patients (43%) demonstrated a normal left ventricular contractile response (LVCR) to exercise; 92 (48%) developed an abnormal LVCR to exercise, including 70 patients with globally abnormal and 22 patients with regional ischemic responses. Of the patients with abnormal responses, 62 patients had anatomic imaging, only 29 of whom had significant OCAD, conferring an overall specificity of ESE for significant OCAD of 21% and accuracy of 52%. Of patients who developed a regionally abnormal response, 89% had significant OCAD. For patients with LBBB who develop a globally abnormal LVCR during ESE, the specificity of ESE for reliably excluding significant OCAD is significantly reduced. ESE appears to be a suboptimal test for the evaluation of OCAD in patients with resting LBBB, as about 50% of patients will have an abnormal response, the majority due to globally abnormal contraction where OCAD cannot be reliably diagnosed. Alternative testing should be considered for the investigation of suspected OCAD in patients with resting LBBB.

Predictive Factors for the Absence of Obstructive Coronary Artery Disease in the Setting of an Abnormal Global Left Ventricular Contractile Response to Exercise

Predictive Factors for the Absence of Obstructive Coronary Artery Disease in the Setting of an Abnormal Global Left Ventricular Contractile Response to Exercise

Response to exercise and mechanical efficiency in non-ischaemic stunning, induced by short-term rapid pacing in dogs: a role for calcium?

Rapid pacing (RP) is a regularly used model to induce heart failure in dogs. The aim of the study was to evaluate Ca2+ handling, left ventricular (LV) contractile response during Ca2+ administration compared to exercise, as well as oxygen consumption and mechanical efficiency after 48h of RP. Fifty-three mongrel dogs were instrumented to measure LV pressure, LV fractional shortening, regional wall thickening and coronary blood flow. Contractile reserve was measured with isoproterenol and intravenous (IV) Ca2+ administration. To assess the function of the sarcoplasmic reticulum (SR), post-extrasystolic potentiation (PESP) and SR Ca2+ uptake were measured. A graded treadmill test was performed in baseline and after RP (n=14). In a separate group of animals (n=5), myocardial performance and oxygen consumption were measured using a wide range of loading conditions. Left ventricular contractility was significantly decreased upon cessation of pacing. The contractile response to isoproterenol was blunted compared to a preserved response to IV Ca2+ . Post-extrasystolic potentiation was slightly increased after RP. Maximal velocity (Vmax ) of SR Ca2+ uptake was unchanged. Contractile response during exercise is attenuated after RP. External work is reduced, whereas oxygen consumption is preserved, provoking a reduced mechanical efficiency. Forty-eight-hours RP provokes a reversible LV dysfunction, while the SR function and response to exogenous Ca2+ are preserved. This is compatible with an intracellular functional remodelling to counteract Ca2+ overload provoked by RP. Left ventricular dysfunction is accompanied by a reduced contractile reserve, but an unchanged oxygen consumption, illustrating an alteration in oxygen utilization.

Abnormal left ventricular contractile response to exercise in the absence of obstructive coronary artery disease is associated with resting left ventricular long-axis dysfunction.

The etiology of reduced left ventricular (LV) ejection fraction after exercise, without obstructive coronary artery disease or other established causes, is unclear. The aims of this study were to determine whether patients undergoing treadmill stress echocardiography with this abnormal LV contractile response to exercise (LVCRE) without established causes have resting LV long-axis dysfunction or microvascular dysfunction and to determine associations with this abnormal LVCRE. Of 5,275 consecutive patients undergoing treadmill stress echocardiography, 1,134 underwent cardiac computed tomography angiography or invasive angiography. Having excluded patients with obstructive coronary artery disease, hypertensive response, submaximal heart rate response, resting LV ejection fraction < 50%, and valvular disease, 110 with "abnormal LVCRE" and 212 with "normal LVCRE" were analyzed. Resting mitral annular velocities were measured to assess LV long-axis function. Myocardial blush grade and corrected Thrombolysis In Myocardial Infarction frame count were determined angiographically to assess microvascular function. Comparing normal LVCRE with abnormal LVCRE, age (mean, 59.7 ± 11.1 vs 61.4 ± 10.0 years), hypertension (53% vs 55%), diabetes (16% vs 20%), and body mass index (mean, 29.1 ± 5.4 vs 29.5 ± 6.4 kg/m(2)) were similar (P > .05). Abnormal LVCRE had reduced resting LV long-axis function with lower septal (mean, 6.1 ± 1.9 vs 7.7 ± 2.2 cm/sec) and lateral (mean, 8.1 ± 2.9 vs 10.4 ± 3.0 cm/sec) e' velocities (P < .001) and larger resting left atrial volumes (mean, 37.3 ± 10.1 vs 31.1 ± 7.2 mL/m(2), P < .001). On multivariate analysis, female gender (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.15-1.99; P < .001), exaggerated chronotropic response (OR, 1.49; 95% CI, 1.09-2.05; P < .001), resting left atrial volume (OR, 2.38; 95% CI, 1.63-3.47; P < .001), and resting lateral e' velocity (OR, 1.70; 95% CI, 1.22-2.49; P = .003) were associated with abnormal LVCRE, but not myocardial blush grade or corrected Thrombolysis In Myocardial Infarction frame count. An abnormal LVCRE in the absence of established causes is associated with resting LV long-axis dysfunction and is usually seen in women.

Abnormal left ventricular exercise stress echocardiography response in the absence of obstructive coronary disease: is subclinical left ventricular myocardial dysfunction another aetiology?

Purpose: Failure of left ventricular (LV) contractile reserve or reduced ejection fraction (EF) post-exercise is an abnormal stress echocardiography (ESE) response. The aetiology of this response in the absence of obstructive coronary artery disease (CAD) is often unclear. We sought to determine the resting echocardiogram characteristics of patients with an abnormal ESE with no known aetiology compared to patients with a normal ESE. Methods: Of 4,542 consecutive patients who underwent ESE for suspected CAD between 2009 and 2012, 521 underwent angiography within 90 days. Having excluded those with obstructive (≥50%) CAD, hypertensive response (>210/105 in men, >190/105 in women), failure to achieve >85% age-predicted heart rate, resting LVEF<50% or >mild valve disease, we identified 110 patients with an abnormal LV contractile response to exercise (abnormal ESE group). These were compared to 90 consecutive patients without obstructive (≥50%) CAD and a normal ESE (normal ESE group) during the same period. LV mass, early diastolic annular velocities (e'), left atrial volume and transmitral Doppler were measured. LVEF was calculated using Simpson's method. Results: Demographic and echocardiogram parameters are summarised in table. In the abnormal ESE group, LVEF decreased post-exercise in 85 (77%) patients and was unchanged in 23 (25%). Comparing normal ESE group vs abnormal ESE group, septal and lateral e' were abnormally reduced in 42 (47%) vs 86 (78%) and 27 (30%) vs 51 (47%) patients (both P<0.001), respectively (defined as >2 standard deviations below age-predicted mean). Demographic & echocardiogram parameters Conclusions: An abnormal LV contractile response to exercise in the absence of obstructive CAD or other established aetiologies is associated with subclinical LV myocardial dysfunction and occurs more commonly in females.

Abnormal Left Ventricular Contractile Response to Exercise Without Obstructive Coronary Disease: A Newly Described Phenomenon Associated with Subclinical Myocardial Dysfunction

Background: Failure of left ventricular (LV) contractile reserve or reduced ejection fraction (EF) post-exercise is an abnormal stress echocardiography (ESE) response. The aetiology in the absence of obstructive coronary artery disease (CAD) or hypertensive response is unclear, but possibly related to either microvascular dysfunction or subclinical myocardial dysfunction. Methods: Of 5,275 consecutive patients undergoing ESE for suspected CAD between 2009 and 2012, 1,134 had angiography within 90 days. Excluding those with obstructive CAD, hypertensive response, failure to achieve target heart rate, resting LVEF < 50% or valvular disease, we identified 110 patients with abnormal LV contractile response (abnormal ESE) and 212 with normal response (normal ESE). Resting echocardiogram mitral annular velocities (e′) were measured to assess subclinical myocardial function. Myocardial blush grade (MBG) and corrected TIMI frame count (CTFC) were determined angiographically to assess microvascular function. Results: Comparing normal ESE vs. abnormal ESE, there was no difference in age (60 ± 11 vs. 61 ± 10), BMI (29.1 ± 5.4 vs. 29.5 ± 6.4), hypertension (53% vs. 55%) or diabetes (16% vs. 20%), but a higher proportion of females with abnormal ESE (82% vs. 53%, p < 0.001). Resting LVEF was similar (60 ± 6% vs. 62 ± 6%, p = 0.05); post-exercise LVEF was lower in abnormal ESE (54 ± 8% vs. 75 ± 6%, p < 0.001). Abnormal ESE had higher LV mass-index (80 ± 21 vs. 73 ± 19 g/m2, p = 0.006), lower septal (6.1 ± 1.9 vs. 7.7 ± 2.2 cm/s) and lateral (8.1 ± 2.9 vs. 10.4 ± 3.0) e′ velocities (p < 0.001), larger left atrial volume index (37.3 ± 10.1 vs. 31.1 ± 7.2 ml/m2, p < 0.001), and lower exercise capacity (8.8 ± 3.0 METS vs. 10.5 ± 4.3 METS, p < 0.001). There was no difference in MBG or CTFC. Conclusions: An abnormal LV contractile response to exercise in the absence of obstructive CAD is most frequently seen in middle-aged females and is associated with subclinical LV myocardial dysfunction, but not with microvascular dysfunction.

Abnormal Left Ventricular Contractile Response to Exercise in the Absence of Obstructive Coronary Disease: A Newly Described Phenomenon Associated With Subclinical Left Ventricular Myocardial Dysfunction

Background: Failure of left ventricular (LV) contractile reserve or reduced ejection fraction (EF) post-exercise represents an abnormal stress echocardiography (ESE) response. The aetiology of this response in the absence of obstructive coronary disease in patients with normal resting LVEF is unclear. We sought to determine whether patients with this response have subclinical LV myocardial dysfunction.Methods: Of 4542 consecutive patients who underwent ESE between January 2009 and January 2012, 521 underwent either CT or invasive angiography within three months. Having excluded those with obstructive (≥50%) coronary disease, hypertensive response to exercise, failure to achieve target heart rate, resting LVEF < 50% and >mild valvular disease, we identified 89 patients who demonstrated an abnormal LV contractile response to exercise. Resting early diastolic mitral annular velocity (e′), left atrial (LA) volume and transmitral Doppler were measured.Results: Of 89 included patients (age 61 ± 10, 83% female, BMI 30 ± 6), 78 underwent ESE to investigate chest pain and/or dyspnoea. Mean Bruce treadmill time was 7.1 ± 2.7 min. LVEF decreased post-exercise in 77 (75%) patients and was unchanged in 22 (25%). Mean resting calculated LVEF 60.0 ± 6.5% fell to 54.7 ± 8.2% post-exercise (p < 0.01). Resting echocardiography findings included: LV mass index 78 ± 21 g/m2, septal e′ 6.1 ± 2.0 cm/s, lateral e′ 8.1 ± 2.9 cm/s, septal E/e′ 11.9 ± 4.0, LA volume 36.8 ± 10.7 ml/m2. Septal and lateral e′ velocities were abnormally reduced in 68 (76%) and 43 (48%) patients respectively (defined as >2 SDs below age-predicted mean). Based on ASE criteria, 76 patients (85%) had LA dilatation.Conclusions: An abnormal LV contractile response to exercise, in the absence of obstructive coronary disease or a hypertensive response, is associated with subclinical LV myocardial dysfunction and predominantly occurs in middle-aged females. Background: Failure of left ventricular (LV) contractile reserve or reduced ejection fraction (EF) post-exercise represents an abnormal stress echocardiography (ESE) response. The aetiology of this response in the absence of obstructive coronary disease in patients with normal resting LVEF is unclear. We sought to determine whether patients with this response have subclinical LV myocardial dysfunction. Methods: Of 4542 consecutive patients who underwent ESE between January 2009 and January 2012, 521 underwent either CT or invasive angiography within three months. Having excluded those with obstructive (≥50%) coronary disease, hypertensive response to exercise, failure to achieve target heart rate, resting LVEF < 50% and >mild valvular disease, we identified 89 patients who demonstrated an abnormal LV contractile response to exercise. Resting early diastolic mitral annular velocity (e′), left atrial (LA) volume and transmitral Doppler were measured. Results: Of 89 included patients (age 61 ± 10, 83% female, BMI 30 ± 6), 78 underwent ESE to investigate chest pain and/or dyspnoea. Mean Bruce treadmill time was 7.1 ± 2.7 min. LVEF decreased post-exercise in 77 (75%) patients and was unchanged in 22 (25%). Mean resting calculated LVEF 60.0 ± 6.5% fell to 54.7 ± 8.2% post-exercise (p < 0.01). Resting echocardiography findings included: LV mass index 78 ± 21 g/m2, septal e′ 6.1 ± 2.0 cm/s, lateral e′ 8.1 ± 2.9 cm/s, septal E/e′ 11.9 ± 4.0, LA volume 36.8 ± 10.7 ml/m2. Septal and lateral e′ velocities were abnormally reduced in 68 (76%) and 43 (48%) patients respectively (defined as >2 SDs below age-predicted mean). Based on ASE criteria, 76 patients (85%) had LA dilatation. Conclusions: An abnormal LV contractile response to exercise, in the absence of obstructive coronary disease or a hypertensive response, is associated with subclinical LV myocardial dysfunction and predominantly occurs in middle-aged females.

Left ventricular morphology and response to beta-adrenergic stimulation in apical ballooning syndrome

The patho-physiology of apical ballooning syndrome (ABS) has not been clearly defined. The aim of this study was to determine whether patients with a history of ABS are more likely to develop left ventricular (LV) mid-cavity or outflow tract obstruction, or have a greater regional LV contractile response to an adrenergic stimulus compared with normal controls. Twenty patients who had recovered from ABS and 15 age-and sex-matched controls had dobutamine stress echocardiography with incremental doses up to 20 µg/kg/min. On average ABS subjects had slightly greater basal LV interventricular septal (1.1 ± 0.24 cm vs. 0.93 ± 0.12, P = 0.03) and posterior wall (1.04 ± 0.16 vs. 0.91 ± 0.11 cm, P = 0.02) diameters compared with controls but LV end-diastolic and end-systolic volumes and LV ejection fraction were similar both at rest and after dobutamine. Regional and global LV contractility, measured with the strain rate and tissue velocity imaging were also similar during the dobutamine infusion up to 10 µg/kg/min in ABS and controls. Mid-LV or LV outflow tract obstruction was not present at rest in any subjects, but was common during peak dobutamine infusion both in the ABS (45%) and controls (53%, P = 0.62). Dynamic LV obstruction with dobutamine is common in those with and without prior ABS. However, this study did not identify a greater individual predisposition to LV obstruction, or a different regional or global LV contractile response to dobutamine in patients with a history of ABS compared with control subjects.

Cardiac performance is impaired in morbidly obese pregnant females

To evaluate the effect of pregnancy on ventricular function in morbidly obese as compared to lean controls. We serially studied 33 obese and non-obese pregnant females with echocardiography during each trimester of pregnancy and after delivery. Two well-validated, relatively load-independent indices of contractility (systolic shortening index and systolic velocity index) were assessed, along with more traditional echocardiographic parameters. ANOVA for repeated measures was used to compare data between sequential studies in the normal and obese pregnant groups. In lean controls, stroke volume increased and contractility was maintained during pregnancy as compared to pre-pregnancy levels. In contrast, both stroke volume and contractility declined significantly by the third trimester in morbidly obese females. There is a maladaptive left ventricular contractile response to pregnancy in morbidly obese patients.

Quantitative left ventricular contractility analysis under stress: a new practical approach in follow-up of hypertensive patients

Excessive sympathetic activity and stress-induced left ventricular (LV) hypercontractility have been described in hypertensive LV hypertrophy. Recent quantitative data have shown that hypertensive LV hypertrophy is associated with preserved global LV function. However, progression of uncontrolled hypertension have detrimental effects on both the ejection fraction (EF) and LV contractile response to stress. Hypertensive LV hypertrophy has some common characteristics, including preserved global LV systolic function and LV volume with heart failure with preserved EF (HFPEF), which makes it difficult to differentiate between the two conditions at rest. Studies suggest that adopting an efficient antihypertensive therapy regimen may positively effect on the LV contractile capability in patients with long-standing hypertension. Evaluation of quantitative LV contractility under stress may be beneficial to differentiate between the hypertensive LV hypertrophy and HFPEF. It may also assist in developing a more effective modality in medical management of patients with hypertensive heart disease.

Repeated inspiratory occlusions acutely impair myocardial function in rats

Repeated episodes of hypoxia and sympathetic activation during obstructive sleep apnoea are implicated in the initiation and progression of cardiovascular diseases, but the acute effects are unknown. We hypothesized that repeated inspiratory occlusions cause acute myocardial dysfunction and injury. In 22 spontaneously breathing pentobarbital-anaesthetized rats, inspiration was occluded for 30 s every 2 min for 3 h. After approximately 1.5 h, mean arterial pressure started to fall; heart rate between occlusions was stable throughout, consistent with only transient increases in sympathetic activity during each occlusion. Three hours of occlusions resulted in ventricular diastolic dysfunction (reduced peak rate of change of ventricular pressure and slower relaxation). Post-occlusions, the left ventricular contractile response to dobutamine was blunted. After 1 h of recovery, left ventricular pressure generation had returned to values no different from those in sham animals in 5 of 9 of the animals. Cardiac myofibrils from rats subjected to occlusions had depressed calcium-activated myosin ATPase activity, indicating myofilament contractile dysfunction that was not due to breakdown of contractile proteins. Haematoxylin and eosin-stained cross-sections revealed multifocal areas of necrosis within the septum and both ventricles. Repeated inspiratory occlusions, analogous to moderately severe obstructive sleep apnoea, acutely cause global cardiac dysfunction with multifocal myocardial infarcts.

Increased Cardiac Adenylyl Cyclase Expression Is Associated With Increased Survival After Myocardial Infarction

Cardiac-directed expression of adenylyl cyclase type VI (AC(VI)) in mice results in structurally normal hearts with normal basal heart rate and function but increased responses to catecholamine stimulation. We tested the hypothesis that increased left ventricular (LV) AC(VI) content would increase mortality after acute myocardial infarction (MI). Transgenic mice with cardiac-directed AC(VI) expression and their transgene-negative littermates (control) underwent coronary ligation, and survival, infarct size, and LV size and function were assessed 1 to 7 days after MI. Mice with increased AC(VI) expression had increased survival (control 41%, AC(VI) 74%; P = 0.004). Infarct size and myocardial apoptotic rates were similar in AC(VI) and control mice; however, AC(VI) mice had less LV dilation (P < 0.001) and increased ejection fractions (P < 0.03). Three days after MI, studies in isolated perfused hearts showed that basal LV +dP/dt was similar, but graded dobutamine infusion was associated with a more robust LV contractile response in AC(VI) mice (P < 0.05). Increased LV function was associated with increases in cAMP generation (P = 0.0002), phospholamban phosphorylation (P < 0.04), sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) affinity for calcium (P < 0.015), and reduced AV block (P = 0.04). In acute MI, increased cardiac AC(VI) content attenuates adverse LV remodeling, preserves LV contractile function, and reduces mortality.

Exhaustion of the Frank–Starling mechanism in conscious dogs with heart failure induced by chronic coronary microembolization

The role of the Frank–Starling mechanism in the regulation of cardiac systolic function in the ischemic failing heart was examined in conscious dogs. Left ventricular (LV) dimension, pressure and systolic function were assessed using surgically implanted instrumentations and non-invasive echocardiogram. Heart failure was induced by daily intra-coronary injections of microspheres for 3–4 weeks via implanted coronary catheters. Chronic coronary embolization resulted in a progressive dilation of the left ventricle (12 ± 3%), increase in LV end-diastolic pressure (118 ± 19%), depression of LV d P / d t max (− 19 ± 4%), fractional shortening (− 36 ± 7%), and cardiac work (− 60 ± 9%), and development of heart failure, while the LV contractile response to dobutamine was depressed. A brief inferior vena caval occlusion in dogs with heart failure decreased LV preload to match the levels attained in their control state and caused a further reduction of LV d P / d t max, fractional shortening, stroke work and cardiac work. Moreover, in response to acute volume loading, the change in the LV end-diastolic dimension–pressure (ΔLVEDD–ΔLVEDP) curve in the failing heart became steeper and shifted significantly to the left, while the increases in LV stroke work and cardiac work were blunted. Thus, our results suggest that the Frank–Starling mechanism is exhausted in heart failure and unable to further respond to increasing volume while it plays an important compensatory role in adaptation to LV dysfunction in heart failure.