Effects of angiotensin-converting enzyme inhibition on mitral regurgitation severity, left ventricular size, and functional capacity.

BACKGROUND: Mitral regurgitation (MR) is a progressive disorder that leads to left ventricular (LV) dilatation and dysfunction. Previous small studies have shown conflicting results regarding the benefits of afterload reduction for MR. METHODS: We assessed by serial echocardiography the effects of ramipril on MR severity and LV size by a number of quantitative methods in 26 asymptomatic patients with moderate to severe MR at baseline and again after 6 months of ramipril treatment. We also evaluated exercise capacity, neurohormonal levels, and the Minnesota Living With Heart Failure score. RESULTS: Despite a significant reduction in blood pressure with ramipril, there was no change in MR severity. MR severity, as assessed by effective regurgitant orifice area, was reduced in individuals with baseline systolic blood pressure (SBP) > or = 140 mm Hg (55.1 +/- 26 vs 37.4 +/- 35.4 mm2, P = .03), but not in individuals with SBP < 140 mm Hg (39.7 +/- 37.7 vs 46.1 +/- 34.1 mm2, P = not significant). Neither LV cavity size, exercise capacity, nor the Minnesota Living With Heart Failure score exhibited a significant change. CONCLUSIONS: Patients with MR do not experience significant changes in MR severity, LV size, or functional status after 6 months of treatment with angiotensin-converting enzyme inhibition. However, patients with SBP > or = 140 mm Hg represent a subgroup that shows reduction in MR. These data are consistent with current American College of Cardiology/American Heart Association guidelines, which reserve the use of afterload reduction for MR patients with systemic hypertension or LV dysfunction.

Prevalence and effect of varicoceles in an elderly population.

OBJECTIVES: The prevalence of a varicocele in the adolescent and young adult populations is approximately 15%. Because other varicose veins increase in prevalence with advanced age, we hypothesized that the incidence of varicoceles in the elderly population would be greater and might affect testicular size, consistency, and function. METHODS: As part of a prostate cancer screening program, we prospectively evaluated 354 men (mean age 60.7 years) by physical examination for the presence of a varicocele, testicular size, and consistency, and measured the serum testosterone level. RESULTS: A varicocele was present bilaterally in 19.8% (70 of 354), left sided only in 22.0% (78 of 354), and right sided only in 1.1% (4 of 354) of patients. Decreased testosterone levels correlated with older age (P = 0.001) and the presence of bilaterally soft testes (P = 0.02) but not the presence of a varicocele. Testes in men with bilateral varicoceles were significantly smaller (P = 0.001) and softer (P = 0.001) than in men without varicoceles. Higher grade varicoceles were more likely to be associated with soft testes (P = 0.001) than were lower grade varicoceles. CONCLUSIONS: The 42% prevalence of varicoceles in our elderly population was greater than that for historic control younger populations, suggesting either an increase with age or examiner sensitivity bias. Varicoceles in the elderly, especially when bilateral, significantly affect testicular consistency (softer) and testicular size (smaller), but do not directly decrease serum testosterone levels. The presence of bilaterally soft testes in elderly men indicates bilateral gonadal dysfunction and may be a physical examination finding associated with decreased serum testosterone.

Significance and relation between magnitude of left ventricular hypertrophy and heart failure symptoms in hypertrophic cardiomyopathy.

In hypertrophic cardiomyopathy (HC), an important subgroup of patients develop progressive and disabling symptoms that are related to heart failure and death. Although a direct relation has been demonstrated between left ventricular (LV) wall thickness and likelihood of sudden and unexpected death (usually in patients who are asymptomatic or mildly symptomatic), it is unresolved whether magnitude of hypertrophy is similarly associated with severity of heart failure. To determine the relation of LV wall thickness to heart failure symptoms in HC, 700 consecutive patients who had HC were assessed by 2-dimensional echocardiography. The relation between maximum level of heart failure symptoms by New York Heart Association functional class and maximum LV wall thickness was not linear but rather parabolic. Therefore, marked symptoms were most commonly associated with moderate degrees of LV hypertrophy (wall thickness 16 to 24 mm; 27%) but less frequently with extreme hypertrophy (>/=30 mm 13%) or mild hypertrophy (

Usefulness of B-type natriuretic peptide assay in the assessment of symptomatic state in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) has a diverse clinical spectrum that often includes progressive heart failure symptoms and disability. Assessment of symptom severity may be highly subjective, encumbered by the heterogeneous clinical presentation. Plasma B-type natriuretic peptide (BNP) has been used widely as an objective marker for heart failure severity and outcome, predominantly in coronary heart disease with ventricular dilatation and systolic dysfunction. METHODS AND RESULTS: We prospectively assessed plasma BNP as a quantitative clinical marker of heart failure severity in 107 consecutive HCM patients. BNP showed a statistically significant relationship to magnitude of functional limitation, assessed by New York Heart Association (NYHA) functional class: I, 136+/-159 pg/mL; II, 338+/-439 pg/mL; and III/IV, 481+/-334 pg/mL (P<0.001). Multivariable analysis showed that BNP was independently related to NYHA class as well as age and left ventricular wall thickness (each with a value of P=0.0001). BNP > or =200 pg/mL was the most reliable predictor of heart failure symptoms, with positive and negative predictive values of 63% and 79%, respectively. BNP power in distinguishing patients with or without heart failure symptoms was less than that for differentiating between no (or only mild) and severe symptoms (area under receiver operating characteristic curve=0.75 and 0.83, respectively). CONCLUSIONS: Plasma BNP is independently related to the presence and magnitude of heart failure symptoms in patients with HCM. As a clinical marker for heart failure, BNP is limited by considerable overlap in values between categories of heart failure severity as well as confounding variables of left ventricular wall thickness and age.

Comparison of standard cardiopulmonary resuscitation versus the combination of active compression-decompression cardiopulmonary resuscitation and an inspiratory impedance threshold device for out-of-hospital cardiac arrest.

BACKGROUND: Active compression-decompression (ACD) CPR combined with an inspiratory impedance threshold device (ITD) improves vital organ blood flow during cardiac arrest. This study compared survival rates with ACD+ITD CPR versus standard manual CPR (S-CPR). METHODS AND RESULTS: A prospective, controlled trial was performed in Mainz, Germany, in which a 2-tiered emergency response included early defibrillation. Patients with out-of-hospital arrest of presumed cardiac pathogenesis were sequentially randomized to ACD+ITD CPR or S-CPR by the advanced life support team after intubation. Rescuers learned which method of CPR to use at the start of each work shift. The primary end point was 1-hour survival after a witnessed arrest. With ACD+ITD CPR (n=103), return of spontaneous circulation and 1- and 24-hour survival rates were 55%, 51%, and 37% versus 37%, 32%, and 22% with S-CPR (n=107) (P=0.016, 0.006, and 0.033, respectively). One- and 24-hour survival rates in witnessed arrests were 55% and 41% with ACD+ITD CPR versus 33% and 23% in control subjects (P=0.011 and 0.019), respectively. One- and 24-hour survival rates in patients with a witnessed arrest in ventricular fibrillation were 68% and 58% after ACD+ITD CPR versus 27% and 23% after S-CPR (P=0.002 and 0.009), respectively. Patients randomized > or =10 minutes after the call for help to the ACD+ITD CPR had a 3 times higher 1-hour survival rate than control subjects (P=0.002). Hospital discharge rates were 18% after ACD+ITD CPR versus 13% in control subjects (P=0.41). In witnessed arrests, overall neurological function trended higher with ACD+ITD CPR versus control subjects (P=0.07). CONCLUSIONS: Compared with S-CPR, ACD+ITD CPR significantly improved short-term survival rates for patients with out-of-hospital cardiac arrest. Additional studies are needed to evaluate potential long-term benefits of ACD+ITD CPR.

Clinical course of hypertrophic cardiomyopathy with survival to advanced age.

OBJECTIVES: This study was designed to clarify and resolve the clinical profile of older patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Adverse consequences of HCM such as sudden death and incapacitating symptoms have been emphasized for the young and middle-aged. METHODS: Long-term outcome of HCM was assessed in a community-based cohort not subject to tertiary center referral bias. RESULTS: Of 312 patients, 73 (23%) achieved normal life expectancy (> or =75 years; range to 96); 44 (14%) were > or =80 years old. Most patients > or =75 years (47; 64%) experienced no or only mild limiting symptoms and lived virtually their entire lives with few HCM-related clinical consequences; 26 patients (36%) experienced severe progressive symptoms. In elderly patients with HCM, diagnosis and symptom onset were considerably delayed to 74 +/- 8 and 70 +/- 11 years, respectively. For patients > or =50 years at diagnosis, the probability of survival for 5, 10, and 15 years was 85 +/- 3%, 74 +/- 4%, and 57 +/- 6%, respectively, and did not significantly differ from a matched general population (p = 0.20). Patients > or =75 years were predominantly women, and had less marked wall thickness and more frequently showed basal outflow obstruction > or =30 mm Hg (compared with those <75 years; p < 0.01 and 0.001, respectively). CONCLUSIONS: Hypertrophic cardiomyopathy is frequently well tolerated and compatible with normal life expectancy, and may remain clinically dormant for long periods of time with symptoms and initial diagnosis deferred until late in life. These observations afford a measure of reassurance to many patients with HCM, a disease for which clinical course is often unfavorable and unpredictable.

Relation of left ventricular thickness to age and gender in hypertrophic cardiomyopathy.

Left ventricular (LV) wall thickening is the most consistent clinical marker of hypertrophic cardiomyopathy (HC), and characteristically increases substantially during adolescence. In this study, we used 2-dimensional echocardiography to develop a cross-sectional profile of LV wall thicknesses in adult patients with HC. We studied a regional community-based cohort of 239 consecutively enrolled patients (aged 18 to 91 years). On average, maximum LV wall thickness decreased relative to increasing age (p = 0.007) within 4 age groups: 22.8 +/- 5.1 mm (18 to 39 years) to 22.1 +/- 5.1 mm (40 to 59 years) to 21.1 +/- 3.7 mm (60 to 74 years) to 20.8 +/- 3.6 mm (>or=75 years). The LV thickness index (summation of wall thicknesses in all 4 segments) also decreased with age (p = 0.017): 63.0 +/- 12.2 mm to 59.8 +/- 11.9 mm to 58.3 +/- 10.4 mm to 57.9 +/- 9.8 mm. Decreasing magnitude of LV hypertrophy was independently associated with increasing age, but not with other relevant disease variables, such as symptoms and outflow obstruction. However, when separated by gender, this inverse relation between age and LV wall thickness was statistically significant only for women (p = 0.007). In conclusion, in an unselected HC cohort, cross-sectional analysis showed a modest but statistically significant inverse relation between age and LV hypertrophy that was largely gender-specific for women. This association constitutes another facet of the natural history of this complex and heterogenous disease and may reflect disproportionate occurrence of premature death in young patients with HC with marked hypertrophy or possibly gradual LV remodeling.

Evidence-based medicine: its effect on treatment recommendations as illustrated by the changing role of postmastectomy irradiation to treat breast cancer.

PURPOSE: To illustrate the effect that the quality of evidence has on clinical practice, we examined how the role of radiotherapy in treating breast cancer has changed over the years as the quality of evidence evolved from anecdotal evidence based on expert opinion to randomized clinical trials and meta-analyses. METHODS: We searched the medical literature for key randomized studies and meta-analyses that have influenced the clinical use of postmastectomy irradiation since the first randomized trials in breast cancer in the 1950s. We discuss how clinical practice changed based on the outcomes of these trials, and then discuss the quality of those trials based on the criteria currently used to assess evidence from randomized trials (CONSORT) and meta-analysis (QUORUM). RESULTS: Evidence published from the early trials and meta-analyses on the role of postmastectomy irradiation had a strong effect on clinical practice. Examination of these studies, however, continues to show significant flaws in trial design that, by today's evidence-based standards, would not meet standards of quality. CONCLUSION: The quality of evidence has a strong effect on shaping clinical practice and needs to be continually assessed. Current guidelines developed to critique both individual randomized trials and meta-analyses are helping to establish high standards for trial design and interpretation. Evidence from older trials that were not guided by well-developed guidelines need to be reviewed, particularly when results from those trials are continually updated and used to generate evidence on which to base current clinical practice.

Bacteria as Risk Markers for Periodontitis.

Specific microbial species have been closely associated with periodontitis. Through longitudinal studies, some of these microbial species have been implicated in the etiology of progressive periodontal disease. Although putative periodontal pathogens are often isolated from individuals with severe periodontitis, they also frequently inhabit the subgingival environment and are not always associated with advanced disease. In this respect, it is becoming increasingly apparent that there is no single etiology of the various periodontal diseases. Destructive periodontal diseases are the result of environmental, host, and bacterial factors. Microorganisms, however, are essential components of any model for progressive periodontitis. This paper selectively reviews bacteria as risk markers for periodontitis. Attention focuses on bacteria in conjunction with behavioral patterns (oral hygiene habits and smoking) and host response (gingival crevicular fluid substances) as risk markers for periodontitis. Prospective studies implicating specific bacteria in progressive periodontitis are addressed and a bacterial risk assessment model for progressive periodontitis is discussed with respect to the interplay between bacterial, environmental, and host markers. J Periodontol 1994; 64:498-510.