Robert N. Belkin

Effect of Amlodipine on Morbidity and Mortality in Severe Chronic Heart Failure

BACKGROUND Previous studies have shown that calcium-channel blockers increase morbidity and mortality in patients with chronic heart failure. We studied the effect of a new calcium-channel blocker, amlodipine, in patients with severe chronic heart failure. METHODS We randomly assigned 1153 patients with severe chronic heart failure and ejection fractions of less than 30 percent to double-blind treatment with either placebo (582 patients) or amlodipine (571 patients) for 6 to 33 months, while their usual therapy was continued. The randomization was stratified on the basis of whether patients had ischemic or nonischemic causes of heart failure. The primary end point of the study was death from any cause and hospitalization for major cardiovascular events. RESULTS Primary end points were reached in 42 percent of the placebo group and 39 percent of the amlodipine group, representing a 9 percent reduction in the combined risk of fatal and nonfatal events with amlodipine (95 percent confidence interval, 24 percent reduction to 10 percent increase; P=0.31). A total of 38 percent of the patients in the placebo group died, as compared with 33 percent of those in the amlodipine group, representing a 16 percent reduction in the risk of death with amlodipine (95 percent confidence interval, 31 percent reduction to 2 percent increase; P=0.07). Among patients with ischemic heart disease, there was no difference between the amlodipine and placebo groups in the occurrence of either end point. In contrast, among patients with nonischemic cardiomyopathy, amlodipine reduced the combined risk of fatal and nonfatal events by 31 percent (P=0.04) and decreased the risk of death by 46 percent (P<0.001). CONCLUSIONS Amlodipine did not increase cardiovascular morbidity or mortality in patients with severe heart failure. The possibility that amlodipine prolongs survival in patients with nonischemic dilated cardiomyopathy requires further study.

Comparison of transesophageal and transthoracic echocardiography with contrast and color flow Doppler in the detection of patent foramen ovale

We directly compared the utility of agitated saline solution contrast echocardiography and color flow Doppler with both transthoracic and transesophageal echocardiography in the detection of patient foramen ovale (PFO). Forty-three patients referred for contrast echocardiography and transesophageal echocardiography were prospectively studied. Three were excluded because of technically inadequate contrast, and two were excluded because of hemodynamically significant atrial septal defect. The remaining 38 patients, who ranged in age from 19 to 73 years, were referred for cerebrovascular events (31), peripheral embolus (5), atrial septal aneurysm (1), and suspected atrial septal defect (1). With either contrast or color flow Doppler, PFO was detected by transthoracic imaging in 9 (24%) of 38 patients compared with 20 (53%) of 38 with transesophageal echo. PFO was present in 1 (3%) of 38 by TTE color flow, 9 (24%) of 38 by TTE contrast, 17 (45%) of 38 by TEE color flow, and 14 (37%) of 38 by TEE contrast. Discordant findings with TEE were the result of contrast-positive, color-negative results in 3 patients and color-positive, contrast-negative results in 6. With TEE contrast used as a diagnostic gold standard, other techniques detected PFO with the following sensitivities, specificities, and positive and negative predictive values: TEE color flow 79%, 75%, 65%, 86%, respectively; TTE contrast 50%, 92%, 78%, 76%, respectively; and TTE color flow 7%, 100%, 50%, 65%, respectively. Thus PFO is detected more frequently with TEE. TEE contrast and color flow Doppler yielded discordant findings in a minority of patients, probably as a result of intrinsic limitations in each technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of amlodipine on mode of death among patients with advanced heart failure in the praise trial

Investigations of calcium antagonists in patients with advanced heart failure have raised concern over an increased risk of worsening heart failure and heart failure deaths. We assessed the effect of amlodipine on cause-specific mortality in such patients enrolled in a randomized, double-blind, placebo-controlled trial. In total, 1,153 patients in New York Heart Association class IIIb or IV heart failure were randomized to receive amlodipine or placebo, along with angiotensin-converting enzyme inhibitors, diuretics, and digitalis. Over a median 14.5 months of follow-up, 413 patients died. Cardiovascular deaths accounted for 89% of fatalities, 50% of which were sudden deaths and 45% of which were due to pump failure, with fewer attributed to myocardial infarction (3.3%) or other cardiovascular causes (1.6%). Amlodipine treatment resulted in a greater relative reduction in sudden deaths (21%) than in pump failure deaths (6.6%) overall. When patients were classified by etiology of heart failure (ischemic or nonischemic), cause-specific mortality did not differ significantly between treatment groups in the ischemic stratum. In the nonischemic stratum, however, sudden deaths and pump failure deaths were reduced by 38% and 45%, respectively, with amlodipine. Thus, when added to digitalis, diuretics, and angiotensin-converting enzyme inhibitors in patients with advanced heart failure, amlodipine appears to have no effect on cause-specific mortality in ischemic cardiomyopathy, but both pump failure and sudden deaths appear to be decreased in nonischemic heart failure patients treated with amlodipine.

Increased prevalence of coronary artery disease, silent myocardial ischemia, complex ventricular arrhythmias, atrial fibrillation, left ventricular hypertrophy, mitral annular calcium, and aortic valve calcium in patients with chronic renal insufficiency.

Cardiovascular morbidity and mortality is high in patients with chronic renal insufficiency. Patients with chronic renal insufficiency have an increased prevalence of coronary artery disease, silent myocardial ischemia, complex ventricular arrhythmias, atrial fibrillation, left ventricular hypertrophy, mitral annular calcium, and aortic valve calcium than patients with normal renal function. These risk factors for cardiovascular morbidity and mortality contribute to the increased incidence of cardiovascular morbidity and mortality seen in patients with chronic renal insufficiency.

Circadian rhythm and sudden death in heart failure: results from Prospective Randomized Amlodipine Survival Trial.

OBJECTIVE The purpose of this study was to address the timing of sudden death in advanced heart failure patients. BACKGROUND Sudden death is a catastrophic event in cardiovascular disease. It has a circadian pattern prominent in the early AM, which has been thought to be due to a surge of sympathetic stimulation. We postulated that the distribution of events in advanced heart failure, with chronic sympathetic activation, would be more uniform implicating other potential mechanisms. METHODS We analyzed data from Prospective Randomized Amlodipine Survival Trial (PRAISE). Sudden deaths were analyzed by time of death in 4-h and 1-h blocks for uniformity of distribution in the entire cohort, and in the prespecified ischemic and nonischemic stratum. Further analyses were undertaken in the treatment groups of amlodipine and placebo, and among those receiving background therapy of aspirin and warfarin. RESULTS Sudden deaths in the overall cohort showed a nonuniform distribution with a PM peak but not an AM peak. The ischemic stratum also showed a PM peak, but sudden deaths within the nonischemic stratum were uniformly distributed. Neither amlodipine treatment nor aspirin or warfarin use altered the distribution. CONCLUSIONS Sudden death in advanced heart failure did not show an AM peak, suggesting that circadian sympathetic activation did not strongly influence these events. The PM peak noted is likely complex in origin and was not affected by antiischemic or antithrombotic medications.

Comparison of sensitivity, specificity, positive predictive value, and negative predictive value of stress testing versus 64-multislice coronary computed tomography angiography in predicting obstructive coronary artery disease diagnosed by coronary angiography.

Sixty-four-multislice coronary computed tomographic angiography (CTA) and coronary angiography were performed in 145 patients (mean age 67 +/- 10 years), and stress testing was performed in 47 of these patients to determine the sensitivity, specificity, positive predictive value, and negative predictive value of coronary CTA and of stress testing in diagnosing obstructive coronary artery disease (CAD) in patients with suspected CAD. In 145 patients, coronary CTA had 98% sensitivity, 74% specificity, 90% positive predictive value, and 94% negative predictive value in diagnosing obstructive CAD. In 47 patients, stress testing had 69% sensitivity, 36% specificity, 78% positive predictive value, and 27% negative predictive value for diagnosing obstructive CAD, whereas coronary CTA had 100% sensitivity, 73% specificity, 92% positive predictive value, and 100% negative predictive value for diagnosing obstructive CAD. In conclusion, coronary CTA has better sensitivity, specificity, positive predictive value, and negative predictive value than stress testing in diagnosing obstructive CAD.

Prevalence of Moderate or Severe Left Ventricular Diastolic Dysfunction in Obese Persons with Obstructive Sleep Apnea

We investigated prior to gastric bypass surgery the prevalence of left ventricular diastolic dysfunction (LVDD) by Doppler and tissue Doppler echocardiography in 14 obese women and in 6 obese men, mean age 45 years, with a mean body mass index of 49 ± 5 kg/m2 who had nocturnal polysomnography for obstructive sleep apnea (OSA). The Doppler and tissue Doppler echocardiographic data were analyzed blindly without knowledge of the clinical characteristics or whether OSA was present or absent. Of 20 patients, 8 (40%) had no OSA, 4 (20%) had mild OSA, and 8 (40%) had moderate or severe OSA. Moderate or severe LVDD was present in 4 of 8 patients (50%) with moderate or severe OSA and in none of 12 patients (0%) with no or mild OSA (p < 0.01). Obese patients with moderate or severe OSA have a higher prevalence of moderate or severe LVDD than obese patients with no or mild OSA.

Aneurysm of the mitral-aortic intervalvular fibrosa complicating infective endocarditis: Preoperative characterization by two-dimensional and color flow Doppler echocardiography, magnetic resonance imaging, and cineangiography

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Outcomes and survival with aortic valve replacement compared with medical therapy in patients with low-, moderate-, and severe-gradient severe aortic stenosis and normal left ventricular ejection fraction.

Background: This study determined outcomes and survival with aortic valve replacement (AVR) versus medical therapy in patients with normal left ventricular ejection fraction (LVEF) with severely reduced aortic valve areas (AVA) but nonsevere mean gradients. Methods: We identified 248 aortic stenosis (AS) patients with LVEF ≥ 50% and echocardiographic AVA < 1.0 cm2. Group 1 had low‐gradient: <30 mmHg mean gradient; group 2 (moderate: 30 to 40 mm Hg); and group 3 (severe: >40 mm). Results: There were 94, 87, and 67 patients in groups 1, 2, and 3. Incidence of death in groups 1, 2, and 3 were 55%, 39%, and 39% (P not significant). Incidence of AVR in groups 1, 2, and 3 were 23%, 53%, and 49% (P < 0.0001 for group 1 vs. 2; P = 0.0003 for group 1 vs. group 3). Incidence of AVR or death was 71%, 77%, and 76% (P not significant). AVR (hazard ratio = 0.30; 95% CI, 0.18, 0.51; P < 0.0001) and mitral annular calcification (hazard ratio = 2.33; 95% CI, 1.40, 3.88; P = 0.001) were independently associated with time to mortality. Kaplan–Meier curves for time to death did not differ significantly among the three groups. Kaplan–Meier survival curves for patients with and without AVR showed patients in all three groups who underwent AVR had significantly greater survival. Conclusion: Among patients with normal LVEF and AVA < 1.0 cm2, overall survival does not differ among those with low‐, moderate‐, or severe‐aortic valve gradients. Survival is significantly improved with AVR, regardless of gradient. (Echocardiography 2011;28:378‐387)

Acute myopericarditis resulting from Lyme disease

left a t r ia l cavi ty function was s tudied by Doppler interrogat ion of mi t ra l inflow after cardioversion of a t r ia l fibrillation, wi th g rea te r and more prolonged depression of a t r ia l function occurring in pa t ien ts who had electrical versus chemical cardioversion. Because TEE was only performed before cardioversion in tha t study, the appra isa l of SEC after cardioversion was not accomplished. In each of these studies, the causal re la t ion of electric cardioversion to impai red a t r ia l and LAA function after the procedure was largely ci rcumstant ia l . The resul ts of the two case s tudies repor ted here demons t ra te t ha t worsening LAA function occurs after spontaneous conversion from a t r ia l f ibri l lat ion and f lut ter to sinus rhy thm, independent of electric or chemical therapeutic interventions. Moreover, SEC can intensify after spontaneous conversion from a t r ia l f ibri l lat ion to sinus rhythm, again wi thout the interference of electric or chemical intervention. Therefore, i t appears as though the mere conversion to s inus rhy thm may be sufficient to predispose the a t r i a l appendage to thrombogenesis and thromboembolism. Increased vagal tone and/or an a t r ia l myopa thy may be under ly ing causes of this phenomenon, a l though a contr ibutory role for electric and/or chemical effects cannot be excluded. The clinical implicat ions of these case studies are pert i nen t to the embolic r i sk associated with cardioversion of a t r ia l a r r h y t h m i a s and to the embolic r isk a t t r ibu ted to va lvu la r and nonvalvular a t r i a l fibrillation. Electric cardioversion should not be abandoned for fear of causing LAA stunning, which may in tu rn place the pa t i en t a t increased r isk for s t roke af ter the procedure. Addit ional ly, i t is unproven tha t pharmacologic cardioversion has any more or less of an effect on LAA function t han electric cardioversion. Therefore, al l pa t ien ts undergoing cardioversion of a t r ia l a r rhy thmias (whether chemical or electric) should be considered a t equivalent r i sk for the development of postcardioversion thromboembolism, and s imi lar ant icoagulat ion s t ra tegies should be used regardless of the modal i ty of cardioversion. Clinical s tudies suppor t this contention because a s imi lar incidence of thromboembolic complications has been repor ted after chemical and electric cardioversion.3, 8 In this repor t we summar ized the findings of two pa t ien ts wi th a t r ia l f ibri l lat ion and f lut ter who demons t ra ted worsening LAA function af ter spontaneous conversion to sinus r h y t h m while being monitored with Doppler TEE. In the pa t ien t ,with spontaneous conversion from a t r ia l f ibri l lat ion into sinus rhy thm, we also observed an increase in the in tens i ty of left a t r ia l SEC after the conversion. These findings demons t ra te the phenomenon of LAA s tunning af ter spontaneous conversion to sinus r h y t h m without use of di rect-current countershock, therefore exonerat ing electric energy as the sole cause of postcardioversion thrombogenesis .