Presence of obesity is associated with lower mortality in elderly patients with implantable cardioverter defibrillator.

BACKGROUND: Higher body mass index (BMI) is associated with greater prevalence of cardiovascular risk factors, yet an inverse relationship between obesity and survival after cardiovascular events has been described. It is unclear whether a similar relationship exists for patients with implantable cardioverter defibrillators (ICDs) at high risk for mortality. We aimed to assess the impact of BMI on mortality and cardiovascular hospitalization in patients with ICD. METHODS: Patients who underwent ICD implantation in 2010-2011 were divided into normal (<25 kg m-2), overweight (25-29.9 kg m-2) and obese (⩾30 kg m-2) groups based on BMI. Clinical parameters were compared and long-term outcomes were determined using χ2 test, Wilcoxon's rank-sum test, logistic regression models and Kaplan-Meier curves. RESULTS: Of 904 patients (mean age 67±13 years), 26% had normal BMI, 32% were overweight and 42% were obese. No significant baseline differences in ventricular ejection fraction, ICD for primary or secondary prevention, history of heart failure, syncope or cardiac arrest existed. Despite a greater prevalence of diabetes, hypertension and prior myocardial infarction, the obese and overweight groups had lower mortality (10.1% and 7.9%, respectively) than the normal group (22.9%, P<0.001). On multivariate logistic regression, BMI in the obese and overweight range (odds ratio (OR): 0.35; 95% confidence interval (CI): 0.21-0.58 and OR: 0.25; 95% CI: 0.13-0.40, respectively) was protective against mortality, whereas history of diabetes (OR: 2.01; 95% CI: 1.30-3.09), myocardial infarction (OR: 1.76; 95% CI: 1.11-2.80), heart failure (OR: 3.88; 95% CI: 1.56-9.66), stroke (OR: 3.19; 95% CI: 1.63-6.23) and history of cardiac arrest (OR: 2.65; 95% CI: 1.37-5.15) were independent risk factors for higher mortality. CONCLUSIONS: A paradoxical relationship between BMI and mortality risk is present in elderly patients with ICD at high risk of sudden death with a lower mortality in obese or overweight patients than in those with normal BMI.

Valvular regurgitation and stenosis: when is surgery required?

Valvular heart disease is a growing public health problem, with an increasing prevalence due to an ageing population. Despite advances, the medical management of symptomatic valvular heart diseases remains suboptimal, necessitating surgical correction. The challenge remains in identifying an asymptomatic or mildly symptomatic patient who will benefit from timely surgery before irreversible changes in cardiac function have occurred. The potential risks of surgery versus watchful expectancy require careful decision-making. This review is a focused update on the existing guidelines and identifies the knowledge gaps and avenues of future research in the management of patients with valvular heart diseases.

Human aortic valve calcification is associated with an osteoblast phenotype.

BACKGROUND: Calcific aortic stenosis is the third most common cardiovascular disease in the United States. We hypothesized that the mechanism for aortic valve calcification is similar to skeletal bone formation and that this process is mediated by an osteoblast-like phenotype. METHODS AND RESULTS: To test this hypothesis, we examined calcified human aortic valves replaced at surgery (n=22) and normal human valves (n=20) removed at time of cardiac transplantation. Contact microradiography and micro-computerized tomography were used to assess the 2-dimensional and 3-dimensional extent of mineralization. Mineralization borders were identified with von Kossa and Goldner's stains. Electron microscopy and energy-dispersive spectroscopy were performed for identification of bone ultrastructure and CaPO4 composition. To analyze for the osteoblast and bone markers, reverse transcriptase-polymerase chain reaction was performed on calcified versus normal human valves for osteopontin, bone sialoprotein, osteocalcin, alkaline phosphatase, and the osteoblast-specific transcription factor Cbfa1. Microradiography and micro-computerized tomography confirmed the presence of calcification in the valve. Special stains for hydroxyapatite and CaPO4 were positive in calcification margins. Electron microscopy identified mineralization, whereas energy-dispersive spectroscopy confirmed the presence of elemental CaPO4. Reverse transcriptase-polymerase chain reaction revealed increased mRNA levels of osteopontin, bone sialoprotein, osteocalcin, and Cbfa1 in the calcified valves. There was no change in alkaline phosphatase mRNA level but an increase in the protein expression in the diseased valves. CONCLUSIONS: These findings support the concept that aortic valve calcification is not a random degenerative process but an active regulated process associated with an osteoblast-like phenotype.

Comparison of ethanol septal reduction therapy with surgical myectomy for the treatment of hypertrophic obstructive cardiomyopathy.

OBJECTIVES: This study was designed to compare the hemodynamic efficacy of nonsurgical septal reduction therapy (NSRT) by intracoronary ethanol with standard therapy (surgical myectomy) for the treatment of hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND: Nonsurgical septal reduction therapy has gained interest as a new treatment modality for patients with drug-refractory symptoms of HOCM; however, its benefits in comparison to surgery are unknown. METHODS: Forty-one consecutive NSRT patients at Baylor College of Medicine with one-year follow-up were compared with age- and gradient-matched septal myectomy patients at the Mayo Clinic. All patients had left ventricular outflow obstruction with a resting gradient > or =40 mm Hg and none had concomitant procedures. RESULTS: There were no baseline differences in New York Heart Association class, severity of mitral regurgitation, use of cardiac medications or exercise capacity. One death occurred during NSRT because of dissection of the left anterior descending artery. At one year, all improvements in both groups were similar. After surgical myectomy, more patients were on medications (p < 0.05) and there was a higher incidence of mild aortic regurgitation (p < 0.05). After NSRT, the incidence of pacemaker implantation for complete heart block was higher (22% vs. 2% in surgery; p = 0.02). However, seven of the nine pacemakers in the NSRT group were implanted before a modified ethanol injection technique and the use of contrast echocardiography. CONCLUSIONS: Nonsurgical septal reduction therapy resulted in a significantly higher incidence of complete heart block, but the risk was reduced with contrast echocardiography and slow ethanol injection. Surgical myectomy resulted in a significantly higher incidence of mild aortic regurgitation. Nonsurgical septal reduction therapy, guided by contrast echocardiography, is an effective procedure for treating patients with HOCM. The hemodynamic and functional improvements at one year are similar to those of surgical myectomy.

Thromboembolic complications after electrical cardioversion in patients with atrial flutter.

PURPOSE: To determine the incidence of thromboembolic complications after cardioversion in patients with atrial flutter. SUBJECTS AND METHODS: We reviewed 615 electrical cardioversions performed electively in 493 patients with atrial flutter. Embolic complications were evaluated during the 30 days after cardioversion. Follow-up data were obtained by follow-up visits and by contacting the treating physician. RESULTS: Anticoagulants had been administered in 415 cardioversions (67%). Cardioversion was successful in 570 procedures (93%). Three embolic events (in 3 patients) occurred in the 30 days after 550 successful cardioversions with completed follow-up (0.6% of successful procedures; 95% confidence interval, 0.1% to 1.6%). Two of the 3 patients had not been anticoagulated, whereas the third patient had subtherapeutic oral anticoagulation. No embolic event occurred in procedures performed with adequate anticoagulation. The incidence of embolism in patients regardless of subtherapeutic anticoagulation was 1% (3 of 303 successful cardioversions). CONCLUSIONS: We observed a low (0.6%) incidence of postcardioversion thromboembolic complications in patients with atrial flutter. Embolic events did not occur in patients with adequate anticoagulation.

Pathophysiologic determinants of third heart sounds: a prospective clinical and Doppler echocardiographic study.

PURPOSE: We sought to determine the importance of a third heart sound (S(3)) and its relation to hemodynamic and valvular dysfunction. SUBJECTS AND METHODS: We prospectively enrolled 580 patients who had isolated valvular regurgitation (mitral, n = 299; aortic, n = 121) or primary left ventricular dysfunction with or without functional mitral regurgitation (n = 160). We analyzed the associations between the clinical finding of an audible S(3) (as noted in routine clinical practice by internal medicine physicians) and hemodynamic alterations measured by comprehensive quantitative Doppler echocardiography. RESULTS: S(3) was more prevalent in patients with primary left ventricular dysfunction (46%, n = 73) than in organic mitral (16%, n = 47) or aortic (12%, n = 14) regurgitation (P <0.001). Patients with an S(3) were more likely to have class III-IV symptoms (55% [74 of 137] vs. 18% [80 of 443] of those without an S(3), P <0.001) and had a higher mean [+/- SD] pulmonary pressure (55 +/- 15 vs. 41 +/- 11 mm Hg, P <0.001). An S(3) was also related to a higher early filling velocity due to a greater filling volume, restrictive filling, or both. An S(3) was a marker of severe regurgitation (regurgitant fraction > or =40%) in patients with primary left ventricular dysfunction (odds ratio [OR] = 2.4; 95% confidence interval [CI]: 1.1 to 5.5), mitral regurgitation (OR = 17; 95% CI: 5.8 to 52), and aortic regurgitation (OR = 7.1; 95% CI: 1.8-28). An S(3) was also associated with restrictive filling in primary left ventricular dysfunction (OR = 3.0; 95% CI, 1.6 to 5.9), marked dilatation in mitral regurgitation (OR = 20; 95% CI: 6.8 to 58), and an ejection fraction (<50%) in aortic regurgitation (OR = 19; 95% CI: 6.0 to 62). CONCLUSION: An audible S(3) is an important clinical finding, indicating severe hemodynamic alterations, and should lead to a comprehensive assessment and consideration of vigorous medical or surgical treatment.

Left ventricular and biventricular pacing in congestive heart failure.

Dual-chamber pacing improved hemodynamics acutely in a subset of patients with left ventricular (LV) dysfunction but conveyed no long-term symptomatic benefit in most. More recently, LV pacing and biventricular (multisite) pacing have been used to improve systolic contractility by altering the electrical and mechanical ventricular activation sequence in patients with severe congestive heart failure (CHF) and intraventricular conduction delay or left bundle branch block (LBBB). Intraventricular conduction delay and LBBB cause dyssynchronous right ventricular and LV contraction and worsen LV dysfunction in cardiomyopathies. Both LV and biventricular cardiac pacing are thought to improve cardiac function in this situation by effecting a more coordinated and efficient ventricular contraction. Short-term hemodynamic studies have shown improvement in LV systolic function, which seems more pronounced with monoventricular LV pacing than with biventricular pacing. Recent clinical studies in limited numbers of patients suggest long-term clinical benefit of biventricular pacing in patients with severe CHF symptoms. Continuing and future studies will demonstrate whether and in which patients LV and biventricular pacing are permanently effective and equivalent and which pacing site within the LV produces the most beneficial hemodynamic results.

Annulus paradoxus: transmitral flow velocity to mitral annular velocity ratio is inversely proportional to pulmonary capillary wedge pressure in patients with constrictive pericarditis.

BACKGROUND: The early diastolic velocity of the mitral annulus (E') is reduced in patients with diastolic dysfunction and increased filling pressures. Because transmitral inflow early velocity (E) increases progressively with higher filling pressures, E/E' has been shown to have a strong positive relationship with pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure. However, previous studies have primarily involved patients without a pericardial abnormality. In constrictive pericarditis (CP), E' is not reduced, despite increased filling pressures. This study evaluated the relationship between E/E' and PCWP in patients with CP. METHODS AND RESULTS: We studied 10 patients (8 men; mean age, 64+/-7 years) with surgically confirmed CP. Doppler echocardiography was performed to measure early and late diastolic transmitral flow velocities. Tissue Doppler echocardiography was performed to measure E'. PCWP was measured with right heart catheterization. All patients were in sinus rhythm. Mean E and E' were 91+/-15 cm/s and 11+/-4 cm/s, respectively. Mean PCWP was 25+/-6 mm Hg. E' was positively correlated with PCWP (r=0.69, P=0.027). There was a significant inverse correlation between E/E' and PCWP (r=-0.74, P=0.014). Despite high left ventricular filling pressures, E/E' (mean, 9+/-4) was <15 in all but 1 patient. CONCLUSIONS: Paradoxical to the positive correlation between E/E' and PCWP in patients with myocardial disease, an inverse relationship was found in patients with CP.

Aortic valve sclerosis and aortic atherosclerosis: different manifestations of the same disease? Insights from a population-based study.

OBJECTIVES: The aim of this study was to examine the association between atherosclerosis risk factors, aortic atherosclerosis and aortic valve abnormalities in the general population. BACKGROUND: Clinical and experimental studies suggest that aortic valve sclerosis (AVS) is a manifestation of the atherosclerotic process. METHODS: Three hundred eighty-one subjects, a sample of the Olmsted County (Minnesota) population, were examined by transthoracic and transesophageal echocardiography. The presence of AVS (thickened valve leaflets), elevated transaortic flow velocities and aortic regurgitation (AR) was determined. The associations between atherosclerosis risk factors, aortic atherosclerosis (imaged by transesophageal echocardiography) and aortic valve abnormalities were examined. RESULTS: Age, male gender, body mass index (odds ratio [OR]: 1.07 per kg/m(2); 95% confidence interval [CI]: 1.02 to 1.12), antihypertensive treatment (OR: 1.93; CI: 1.12 to 3.32) and plasma homocysteine levels (OR: 1.89 per twofold increase; CI: 0.99 to 3.61) were independently associated with an increased risk of AVS. Age, body mass index and pulse pressure (OR: 1.21 per 10 mm Hg; CI: 1.00 to 1.46) were associated with elevated (upper quintile) transaortic velocities, whereas only age was independently associated with AR. Sinotubular junction sclerosis (p = 0.001) and atherosclerosis of the ascending aorta (p = 0.03) were independently associated with AVS and elevated transaortic velocities, respectively. CONCLUSIONS: Atherosclerosis risk factors and proximal aortic atherosclerosis are independently associated with aortic valve abnormalities in the general population. These observations suggest that AVS is an atherosclerosis-like process involving the aortic valve.

Experimental hypercholesterolemia induces apoptosis in the aortic valve.

BACKGROUND AND AIM OF THE STUDY: Aortic valve disease is presently the number one indication for valve replacement in the United States, yet its molecular mechanisms remain unknown. As apoptosis (programmed cell death) occurs in degenerative disease states, it was postulated that experimental hypercholesterolemia is associated with apoptosis in rabbit aortic valves. METHODS: New Zealand White rabbits (n = 8) were fed a 1% cholesterol diet for 12 weeks; control rabbits (n = 8) were fed a normal diet. After sacrifice of the animals, the aortic valves were dissected. Apoptosis was identified in the valvular lesion by TdT-mediated dUTP-biotin nick end-labeling (TUNEL) technique, and confirmed with transmission electron microscopy. The number of apoptotic cells was measured by computed morphometry. RESULTS: Valves from hypercholesterolemic rabbits showed an increase in apoptosis. TUNEL staining was identified in the atherosclerotic layer of hypercholesterolemic valves (0.1% of cells), but not in the cells of controls (p <0.0001). CONCLUSION: Apoptosis is increased in rabbit aortic valves during experimental hypercholesterolemia. If fatal cellular degeneration occurs in hypercholesterolemic valve disease, these data suggest that apoptosis may play a role in the mechanism of valvular disease.

Ischemic mitral regurgitation: long-term outcome and prognostic implications with quantitative Doppler assessment.

BACKGROUND: Myocardial infarction (MI) can directly cause ischemic mitral regurgitation (IMR), which has been touted as an indicator of poor prognosis in acute and early phases after MI. However, in the chronic post-MI phase, prognostic implications of IMR presence and degree are poorly defined. METHODS AND RESULTS: We analyzed 303 patients with previous (>16 days) Q-wave MI by ECG who underwent transthoracic echocardiography: 194 with IMR quantitatively assessed in routine practice and 109 without IMR matched for baseline age (71+/-11 versus 70+/-9 years, P=0.20), sex, and ejection fraction (EF, 33+/-14% versus 34+/-11%, P=0.14). In IMR patients, regurgitant volume (RVol) and effective regurgitant orifice (ERO) area were 36+/-24 mL/beat and 21+/-12 mm(2), respectively. After 5 years, total mortality and cardiac mortality for patients with IMR (62+/-5% and 50+/-6%, respectively) were higher than for those without IMR (39+/-6% and 30+/-5%, respectively) (both P<0.001). In multivariate analysis, independently of all baseline characteristics, particularly age and EF, the adjusted relative risks of total and cardiac mortality associated with the presence of IMR (1.88, P=0.003 and 1.83, P=0.014, respectively) and quantified degree of IMR defined by RVol >/=30 mL (2.05, P=0.002 and 2.01, P=0.009) and by ERO >/=20 mm(2) (2.23, P=0.003 and 2.38, P=0.004) were high. CONCLUSIONS: In the chronic phase after MI, IMR presence is associated with excess mortality independently of baseline characteristics and degree of ventricular dysfunction. The mortality risk is related directly to the degree of IMR as defined by ERO and RVol. Therefore, IMR detection and quantification provide major information for risk stratification and clinical decision making in the chronic post-MI phase.

Timing of surgery in patients with chronic, severe mitral regurgitation.

Patients with severe mitral regurgitation (MR) who are managed conservatively sustain excess mortality and morbidity. With improved mortality and morbidity rates being achieved with surgical management, cardiologists and cardiac surgeons are becoming more aggressive in treating patients with severe MR with surgery. Recent data indicate that even in the absence of symptoms or left ventricular dysfunction, surgery should be offered as a treatment for MR, provided that the regurgitation is severe, the valve seems to be repairable, and the surgeon is experienced in valve repair and is aided by intraoperative transesophageal echocardiography.

Effect of losartan on degree of mitral regurgitation quantified by echocardiography.

The objective of this study was to determine the effect of oral losartan on the degree of mitral regurgitation (MR). The regurgitant volume and effective regurgitant orifice were quantified using 3 methods (flow convergence, quantitative Doppler, and quantitative 2-dimensional echocardiography) in 32 patients (26 men, mean age 67 +/- 14 years) with MR, both at baseline and 4 hours after losartan (50 mg orally). Twenty-eight patients were also reevaluated after 1 month of continued treatment with losartan (50 mg/day). With treatment, systolic blood pressure decreased from 143 +/- 16 to 130 +/- 18 mm Hg and left ventricular end-systolic wall stress from 173 +/- 46 to 156 +/- 44 g/cm2 (both p < 0.001). With treatment, regurgitant volume decreased (from 77 +/- 28 to 64 +/- 26 ml, - 18 +/- 10%; p < 0.001) in direct relation to the effective regurgitant orifice change (from 43 +/- 16 to 37 +/- 15 mm2, -17 +/- 10%; p < 0.001) but without significant change in regurgitant gradient or duration. Wide individual variability in response was observed unrelated to the magnitude of blood pressure changes. Larger reduction in regurgitant volume was observed in patients with a marked decrease in wall stress (r = 0.47, p = 0.01) and higher baseline end-diastolic volume index (r = -0.38, p = 0.03) and regurgitant volume (r = -0.45, p = 0.01). Acute improvements were sustained and unchanged at 1 month (all p > 0.15). Treatment of MR using the angiotensin receptor antagonist losartan produces a significant and sustained decrease in the degree of MR, with decreases in regurgitant volume and effective regurgitant orifice. However, the changes are of modest and variable magnitude.

Reoperation for prosthetic aortic valve obstruction in the era of echocardiography: trends in diagnostic testing and comparison with surgical findings.

OBJECTIVES: We sought to: 1) identify trends in the diagnostic testing of patients with prosthetic aortic valve (AVR) obstruction who undergo reoperation and 2) compare diagnostic test results with pathologic findings at surgery. BACKGROUND: It is unclear whether Doppler transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) have reduced hemodynamic catheterization rates. METHODS: We reviewed 92 consecutive cases ofAVR reoperation at a single center from 1989 to 1998, comparing 49 cases of mechanical AVR obstruction (group A) to 43 cases of bioprosthetic obstruction (group B). Preoperative Doppler TTE was performed in all cases. RESULTS: In group A cases, there was a marginally significant trend towards lower catheterization rates for the Gorlin AVR area, from 36% in 1989 to 1990 to 10% in 1997 to 1998 (p = 0.07), but diagnostic TEE utilization (47% of cases) did not vary. The cause of mechanical AVR obstruction was pannus in 26 cases (53%), mismatch (P-PM) in 19 (39%) and thrombosis in 4 (8%). The mechanism (pannus/thrombus vs. mismatch) was identified in 10% by TTE and 49% by TEE (p < 0.001). In group B cases, hemodynamic catheterization rates (21%) and diagnostic TEE utilization (21%) did not vary with time. Obstruction was caused by structural degeneration in 37 cases (86%), thrombosis in 3 (7%), mismatch in 2 (5%) and pannus in 1 (2%). The mechanism was correctly identified in 63% by TTE and in 81% by TEE (p = 0.18). CONCLUSIONS: Doppler TTE is the primary means to diagnose AVR obstruction; hemodynamic catheterization is not routinely needed. In unselected patients with mechanical AVR obstruction, TEE differentiation of pannus or thrombus from mismatch is challenging.

Five or more years of survival in patients with primary systemic amyloidosis and biopsy-proven cardiac involvement.

Survival of > or =5 years was seen in 8 of 153 patients (5%) with primary systemic amyloidosis and cardiac involvement. All patients with survival of >5 years received chemotherapy and all but 1 had an objective chemotherapeutic response.

Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous Doppler-catheterization study.

BACKGROUND: Noninvasive assessment of diastolic filling by Doppler echocardiography provides important information about left ventricular (LV) status in selected subsets of patients. This study was designed to assess whether mitral annular velocities as assessed by tissue Doppler imaging are associated with invasive measures of diastolic LV performance and whether additional information is gained over traditional Doppler variables. METHODS AND RESULTS: One hundred consecutive patients referred for cardiac catheterization underwent simultaneous Doppler interrogation. Invasive measurements of LV pressures were obtained with micromanometer-tipped catheters, and the mean LV diastolic pressure (M-LVDP) was used as a surrogate for mean left atrial pressure. Doppler signals from the mitral inflow, pulmonary venous inflow, and TDI of the mitral annulus were obtained. Isolated parameters of transmitral flow correlated with M-LVDP only when ejection fraction <50%. The ratio of mitral velocity to early diastolic velocity of the mitral annulus (E/E') showed a better correlation with M-LVDP than did other Doppler variables for all levels of systolic function. E/E' <8 accurately predicted normal M-LVDP, and E/E' >15 identified increased M-LVDP. Wide variability was present in those with E/E' of 8 to 15. A subset of those patients with E/E' 8 to 15 could be further defined by use of other Doppler data. CONCLUSIONS: The combination of tissue Doppler imaging of the mitral annulus and mitral inflow velocity curves provides better estimates of LV filling pressures than other methods (pulmonary vein, preload reduction). However, accurate prediction of filling pressures for an individual patient requires a stepwise approach incorporating all available data.