Marek Orban

Dynamic Changes of Left Ventricular Performance and Left Atrial Volume Induced by the Mueller Maneuver in Healthy Young Adults and Implications for Obstructive Sleep Apnea, Atrial Fibrillation, and Heart Failure

Using the Mueller maneuver (MM) to simulate obstructive sleep apnea (OSA), our aim was to investigate acute changes in left-sided cardiac morphologic characteristics and function which might develop with apneas occurring during sleep. Strong evidence supports a relation between OSA and both atrial fibrillation and heart failure. However, acute effects of airway obstruction on cardiac structure and function have not been well defined. In addition, it is unclear how OSA might contribute to the development of atrial fibrillation and heart failure. Echocardiography was used in healthy young adults to measure various parameters of cardiac structure and function. Subjects were studied at baseline, during, and immediately after performance of the MM and after a 10-minute recovery. Continuous heart rate, blood pressure, and pulse oximetry measurements were made. During the MM, left atrial (LA) volume index markedly decreased. Left ventricular (LV) end-systolic dimension increased in association with a decrease in LV ejection fraction. On release of the maneuver, there was a compensatory increase in blood flow to the left side of the heart, with stroke volume, ejection fraction, and cardiac output exceeding baseline. After 10 minutes of recovery, all parameters returned to baseline. In conclusion, sudden imposition of severe negative intrathoracic pressure led to an abrupt decrease in LA volume and a decrease in LV systolic performance. These changes reflected an increase in LV afterload. Repeated swings in afterload burden and chamber volumes may have implications for the future development of atrial fibrillation and heart failure.

Under-diagnosis of Sleep Apnea in Patients after Acute Myocardial Infarction

TO THE EDITOR: Obstructive sleep apnea (OSA) is highly prevalent in the general population and has been associated with arrhythmias, hypertension, stroke, and heart failure (1). Identification of OSA in cardiovascular patients is especially important as untreated OSA may be accompanied by increased cardiovascular events, and this risk may be attenuated by treatment with continuous positive airway pressure (CPAP)(2). We sought to investigate how the rates of recognition and diagnosis of obstructive sleep apnea compare to the actual prevalence of OSA in patients after myocardial infarction (MI). This study comprised two parts: a chart review of consecutive patients presenting with acute MI, and a prospective evaluation of MI patients who were recruited to undergo polysomnography. These studies were approved by the Institutional Review Board. First, we reviewed the medical records of 798 consecutive patients who were hospitalized with a diagnosis of acute MI between January and September 2007. Electronic records, including admission and dismissal notes were searched for diagnosed or suspected sleep disordered breathing, and especially for mention of OSA during the MI hospitalization. In the event of several hospital admissions for the same patient, only the first admission was used in our analysis. We further prospectively studied 74 patients who were hospitalized with acute myocardial infarction between 2004 and 2008, and were recruited to undergo attended overnight polysomnography, which is the gold standard in the diagnosis of OSA (Compumedics Siesta Wireless Sleep Recorder, Oxford Instruments, UK). All polysomnographies were performed within 6 weeks of the MI hospitalization, and scored by standard criteria (1). OSA was defined as present when the apnea hypopnea index (AHI) was >5. The diagnosis of MI was based on standard guidelines, and was made by the attending physicians who were blinded to this study. Patients were approached during their MI hospitalization, and their participation was based on their consent and availability of the study personnel and equipment. There was no systematic selection for specific demographic or patient characteristics. A review of electronic and paper records of these patients was also performed in similar fashion to that of the first part of our study. Between January and September 2007 there were 798 patients admitted to our institution with the diagnosis of acute MI. The mean age of this cohort was 69±14 years, and 512 (64%) were male. Diagnosed and suspected OSA was recorded in 97 (12%) patient records. The prospective cohort of 74 patients had a mean age of 62±13 years, and 46 (78%) were male. On review of their hospital records, 10 (14%) had documentation of diagnosed or suspected OSA. All of these patients underwent overnight polysomnography (PSG). For this group the mean AHI was 17±18 events/hour. OSA was present in 51 (69%), and severe OSA (AHI >15) in 30 (41%) patients. The main finding of this study was the low rate of documented or suspected OSA in patients hospitalized for acute MI, contrasting with the high prevalence of OSA in those in whom we conducted prospective PSG studies. This suggests a lack of awareness and recognition of OSA during treatment of acute MI. A high prevalence of OSA in the unselected general population has been well documented (1). Our results suggest that only 12 percent of patients hospitalized with acute MI had documentation of diagnosed or suspected OSA. When prospectively evaluated by overnight PSG a subgroup of patients had a much higher actual prevalence of OSA (over two thirds had at least mild OSA) but even in these patients with proven sleep apnea the possibility of OSA was documented in only 14 percent of patients. There are several limitations to our study. First, documentation in the medical record does not necessarily reflect the entire scope of medical evaluation; it is possible that in some patients OSA was suspected and they were verbally recommended to have an OSA evaluation which was not documented in the records, or this was left for a follow-up visit. Even so, it would be advantageous to arrange for screening for OSA during the hospitalization, just as we routinely initiate aspirin, beta-blocker, statin, and ACE inhibitor therapy before patient discharge. Cardiovascular disease patients with untreated severe OSA are thought to have worse cardiovascular outcomes (2,3), which may be improved with CPAP. Randomized controlled trials testing this assumption are lacking. Demonstrated beneficial effects of CPAP could lead to significant practice and guidelines changes. An absence of such clinical trials may help explain the relatively low awareness of OSA as an important consideration in the patient with MI.

Modest Visceral Fat Gain Causes Endothelial Dysfunction in Healthy Humans

OBJECTIVES The aim of this study was to determine the impact of fat gain and its distribution on endothelial function in lean healthy humans. BACKGROUND Endothelial dysfunction has been identified as an independent predictor of cardiovascular events. Whether fat gain impairs endothelial function is unknown. METHODS A randomized controlled study was conducted to assess the effects of fat gain on endothelial function. Forty-three normal-weight healthy volunteers were recruited (mean age 29 years; 18 women). Subjects were assigned to gain weight (approximately 4 kg) (n=35) or to maintain weight (n=8). Endothelial function (brachial artery flow-mediated dilation [FMD]) was measured at baseline, after fat gain (8 weeks), and after weight loss (16 weeks) for fat gainers and at baseline and follow-up (8 weeks) for weight maintainers. Body composition was measured by dual-energy X-ray absorptiometry and abdominal computed tomographic scans. RESULTS After an average weight gain of 4.1 kg, fat gainers significantly increased their total, visceral, and subcutaneous fat. Blood pressure and overnight polysomnography did not change after fat gain or loss. FMD remained unchanged in weight maintainers. FMD decreased in fat gainers (9.1+/-3% vs. 7.8+/-3.2%, p=0.003) but recovered to baseline when subjects shed the gained weight. There was a significant correlation between the decrease in FMD and the increase in visceral fat gain (rho=-0.42, p=0.004), but not with subcutaneous fat gain (rho=-0.22, p=0.15). CONCLUSIONS In normal-weight healthy young subjects, modest fat gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial function recovers after weight loss. Increased visceral rather than subcutaneous fat predicts endothelial dysfunction. (Fat Gain and Cardiovascular Disease Mechanisms; NCT00589498).

Left Ventricular Mechanics in Idiopathic Dilated Cardiomyopathy: Systolic-Diastolic Coupling and Torsion

BACKGROUND In idiopathic dilated cardiomyopathy (IDC), myocardial deformational parameters and their mutual relationships remain incompletely characterized. METHODS Thirty-seven patients with IDC underwent two-dimensional speckle-tracking echocardiography (2D-STE) to assess left ventricular rotation, torsion, and longitudinal, circumferential, and radial systolic and diastolic strains and strain rates. Additionally, 2D-STE was performed in 14 controls. RESULTS All deformational parameters on 2D-STE were significantly lower in patients with IDC compared with controls. Seven patients exhibited opposite basal (positive, counterclockwise) and 11 patients exhibited opposite apical (negative, clockwise) rotation at end-systole. Circumferential, radial, and longitudinal early diastolic strain rates were correlated most strongly with the corresponding spatial components of systolic deformation. CONCLUSION In patients IDC, all torsional, systolic, and diastolic deformational parameters were decreased. Corresponding three-dimensional components of systolic and diastolic deformations were closely coupled. Considerable variation in the direction of basal and apical rotation exists in a subset of patients with IDC.

Changes in Left and Right Ventricular Mechanics During the Mueller Maneuver in Healthy Adults A Possible Mechanism for Abnormal Cardiac Function in Patients With Obstructive Sleep Apnea

Background—Obstructive sleep apnea is highly prevalent in patients with cardiovascular disease and has detrimental effects on systolic and diastolic function of the ventricles. In this research, the changes in strain (S) and strain rate (SR) during the performance of the Mueller maneuver (MM) in an effort to better understand how negative intrathoracic pressures affect ventricular mechanics. Methods and Results—The MM was performed to maintain a target intrathoracic pressure of −40 mm Hg. Echocardiography was used to measure various parameters of cardiac structure and function. Myocardial deformation measurements were performed using tissue speckle tracking. Twenty-four healthy subjects (9 women; mean age, 30±6 years) were studied. Global left ventricular longitudinal S in systole and SR in early filling were significantly decreased during the MM (S: baseline, −17.0±1.6%; MM, −14.5±2.2%; P<0.0001, SR: baseline, 1.09±0.20 s−1; MM, 0.92±0.21 s−1; P=0.01). Global right ventricular longitudinal S was also significantly decreased during the MM (baseline, −22.0±3.1%; MM, −17.2±2.5%; P<0.0001), as was global right ventricular longitudinal systolic SR (baseline, −1.34±0.35 s−1; MM, −1.02±0.21 s−1; P=0.0006). Conclusions—Left ventricular and right ventricular longitudinal deformation are significantly reduced during the MM. These results suggest that negative intrathoracic pressure during apnea may contribute to changes in myocardial mechanics. These results could help explain the observed changes in left ventricular and right ventricular mechanics in patients with obstructive sleep apnea.

Short-term Effects of Cardiac Resynchronization Therapy on Sleep-Disordered Breathing in Patients With Systolic Heart Failure

OBJECTIVES We evaluated the short-term effect of cardiac resynchronization therapy (CRT) on sleep apnea in patients with systolic heart failure. BACKGROUND Sleep-disordered breathing is common in patients with left ventricular systolic dysfunction. METHODS Twelve patients (mean [+/-SE] age, 59.6+/-7.8 years; mean left ventricular ejection fraction, 28.0+/-2.8%) with an implanted atrial-synchronized biventricular pacemaker for the treatment of left ventricular systolic dysfunction were selected and studied. Each subject underwent polysomnography on 3 consecutive nights with CRT on the first night, CRT off the second night, and CRT on the third night. Echocardiography was performed prior to each polysomnogram. RESULTS The central sleep event index (ie, the number of central sleep apneas [CSAs] and hypopneas per hour of sleep) score was lower with CRT compared to that without CRT (mean central sleep event index score with CRT on, 6.9+/-1.7 events per hour of sleep; mean central sleep event index score with CRT off, 14.3+/-2.9 events per hour of sleep; mean central sleep event index score with CRT on, 8.1+/-1.5 events per hour of sleep; p<0.001). Similarly, the cumulative duration of central sleep events (the number of minutes per hour of sleep during CRT) was one half that observed without CRT (CRT on, 2.8+/-0.7 min per hour of sleep; CRT OFF 6.2+/-1.2 min per hour of sleep; CRT ON 3.1+/-0.7 min per hour of sleep; p<0.001). There was a significant correlation between mitral regurgitant volume and central sleep event index on all three nights (r>or=0.77; p<0.01). CONCLUSIONS CRT reduces CSA severity in the short term. This reduction correlated significantly with the CRT-mediated reduction of mitral regurgitation.

High Prevalence of Abnormal Nocturnal Oximetry in Patients With Hypertrophic Cardiomyopathy

OBJECTIVES We sought to determine the prevalence of nocturnal oxygen desaturation and obstructive sleep apnea (OSA) in a population of patients with hypertrophic cardiomyopathy (HCM). BACKGROUND The coexistence of sleep apnea and HCM, 2 common cardiovascular conditions, has been largely unrecognized in the treatment of patients with HCM. The nocturnal hypoxia-induced hyperadrenergic state in OSA is expected to worsen hemodynamics and outcomes in HCM. METHODS One hundred subjects with HCM between June 1, 2006, and July 14, 2008, were screened with nocturnal oximetry. Clinical variables were collected for statistical analysis. Oximetry was classified abnormal (suspicion of sleep-disordered breathing) in the presence of repetitive desaturation (> or =5 events/h) followed by a rapid return to baseline oxygen saturation (SaO(2)) level with a decrease of > or =4% and threshold of 90%. RESULTS Seventy-one (71%) patients with HCM had abnormal nocturnal oximetry (71 +/- 9%, 95% confidence interval: 62% to 80%). Subjects with abnormal oximetry were older (age 59.5 +/- 15.3 years) and more were hypertensive (n = 39 [55%]) than those with normal oximetry (age 45.8 +/- 18.5 years, n = 9 [31%], p < 0.001, p = 0.03). Patients with HCM were more symptomatic in the presence of abnormal oximetry (New York Heart Association functional class II to III) (62% vs. 83%, p = 0.023). HCM patients had a higher prevalence of abnormal nocturnal oximetry (n = 71, 71%) compared with a control group of similar age and sex distribution (n = 49, 49%) (p = 0.001). CONCLUSIONS Abnormal nocturnal oximetry is common in patients with HCM, suggesting that OSA is prevalent. OSA may impact hemodynamics and symptoms in HCM. Further studies are needed to determine the long-term benefit of OSA treatment on hemodynamics and disease progression in HCM.

Relation of Chronic Obstructive Pulmonary Disease to Atrial and Ventricular Arrhythmias

Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality, yet the exact pathophysiological links remain unclear. Whether the presence and severity of COPD are associated with atrial or ventricular arrhythmias recorded on continuous electrocardiographic monitoring is unknown. We identified consecutive adult patients who underwent clinically indicated pulmonary function testing as well as 24-hour Holter monitoring at the Mayo Clinic, Rochester, from 2000 to 2009. Demographic data and relevant co-morbidities were gathered from the electronic medical record; severity of COPD was classified according to the GOLD classification, and arrhythmias were classified in concordance with the current clinical guidelines. From 7,441 patients who were included (age 64±16 years, 49% woman, 92% Caucasian), COPD was diagnosed in 3,121 (41.9%). Compared with those without COPD, the presence and severity of COPD were associated with increased likelihood of atrial fibrillation/atrial flutter (AF/AFL; 23.3% vs 11.0%, respectively, p<0.0001), nonsustained ventricular tachycardia (NSVT; 13.0% vs 5.9%, respectively, p<0.0001), and sustained ventricular tachycardia (0.9% vs 1.6%, respectively, p<0.0001). COPD remained a significant predictor of AF/AFL and NSVT (p<0.0001 and p<0.0001, respectively) after adjusting for age, gender, tobacco use, obesity, hypertension, coronary artery disease, heart failure, diabetes, anemia, cancer, chronic kidney disease, and rate/rhythm control medications. In conclusion, the independent association between the presence and severity of COPD and arrhythmias (AF/AFL and NSVT) provides further insight into the markedly increased cardiovascular mortality of patients with COPD. Further studies should explore which anti-arrhythmic strategies would best apply to the patients with COPD.

Estimation of left ventricular filling pressures by speckle tracking echocardiography in patients with idiopathic dilated cardiomyopathy

AIMS the ratio of early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (E(a)) is frequently used to predict an increase in left ventricular filling pressure (LVFP). However, this approach has several limitations. The aim of this study was to test whether additional information is gained by new echocardiographic indexes utilizing strain and strain rate (SR) derived from 2-dimensional speckle tracking echocardiography (2D-STE) for the estimation of LVFP. METHODS AND RESULTS fifty-one patients with idiopathic dilated cardiomyopathy (IDC) underwent pulsed-wave tissue Doppler echocardiography and 2D-STE performed simultaneously with right heart catheterization. Receiver operating characteristic analysis showed that circumferential strain and the SR during late diastolic LV filling (0.956 and 0.951, both P = 0.001), E/circumferential SR at early diastolic LV filling (0.949, P = 0.001), and E/circumferential strain at the time of peak E-wave (0.948, P = 0.001) had greater area under the curve than the E/E(a) ratio (0.911, P = 0.001) for the prediction of pulmonary capillary wedge pressure > 12 mmHg. CONCLUSION when compared with the E/E(a) ratio, several 2D-STE-derived parameters better estimated the increase in LVFP in patients with IDC.

Interactions Between Sleep Disordered Breathing and Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy

The aim of this study was to investigate whether patients with hypertrophic cardiomyopathy (HC) and sleep disordered breathing (SDB) have a higher prevalence of atrial fibrillation (AF) compared to patients with HC without SDB. HC is associated with a high prevalence of AF that contributes to increased morbidity and mortality. SDB is strongly associated with a higher incidence, prevalence, and recurrence of AF in patients without HC. Whether this association also applies to patients with HC is not known. Overnight oximetry was prospectively performed on 91 consecutive patients with echocardiographically confirmed HC. The presence or absence of AF in this population was correlated with the oximetric findings. SDB was associated with a higher prevalence of AF (40% vs 11%, p = 0.005). In addition, SDB was accompanied by significantly increased left atrial volume index (58 +/- 19 vs 42 +/- 13 ml/m(2), p = 0.0002). Increasing severity of SDB was correlated with higher AF prevalence and with increase in left atrial volume index. These associations remained significant even after accounting for potential confounders in a multivariate analysis. In conclusion, these findings suggest that the presence and severity of SDB may influence left atrial volume index and the prevalence of AF in patients with HC. SDB may therefore be an important and potentially modifiable cause of morbidity and mortality in this population.