Paul N. Casale

Relation of Left Ventricular Mass and Geometry to Morbidity and Mortality in Uncomplicated Essential Hypertension

OBJECTIVE To assess the prognostic significance of left ventricular mass and geometry in initially healthy persons with essential hypertension. DESIGN An observational study of a prospectively identified cohort. SETTING University medical center. PATIENTS Two hundred and eighty patients with essential hypertension and no pre-existing cardiac disease were evaluated using echocardiography between 1976 and 1981. Two hundred and fifty-three subjects or their family members (90%) were contacted for a follow-up interview an average of 10.2 years after the initial echocardiogram was obtained; the survival status of 27 patients lost to follow-up was ascertained using National Death Index data. MEASUREMENTS AND MAIN RESULTS Left ventricular mass exceeded 125 g/m2 in 69 of 253 patients (27%). Cardiovascular events occurred in a higher proportion of patients with than without left ventricular hypertrophy (26% compared with 12%; P = 0.006). Patients with increased ventricular mass were also at higher risk for cardiovascular death (14% compared with 0.5%; P less than 0.001) and all-cause mortality (16% compared with 2%; P = 0.001). Electrocardiographic left ventricular hypertrophy did not predict risk. Patients with normal left ventricular geometry had the fewest adverse outcomes (no cardiac deaths; morbid events in 11%), and those with concentric hypertrophy had the most (death in 21%; morbid events in 31%). In a multivariate analysis, only age and left ventricular mass--but not gender, blood pressure, or serum cholesterol level--independently predicted all three outcome measures. CONCLUSIONS Echocardiographically determined left ventricular mass and geometry stratify risk in patients with essential hypertension independently of and more strongly than blood pressure or other potentially reversible risk factors and may help to stratify the need for intensive treatment.

Value of Echocardiographic Measurement of Left Ventricular Mass in Predicting Cardiovascular Morbid Events in Hypertensive Men

To assess whether echocardiographic and electrocardiographic detection of left ventricular hypertrophy could predict cardiovascular morbid events in patients with uncomplicated essential hypertension, we followed 140 men for a mean of 4.8 years. Initial echocardiographic measurements of left ventricular mass were normal (less than 125 g/m2 body surface area) in 111 patients and revealed hypertrophy in 29 patients. Morbid events occurred in more patients with hypertrophy on echocardiography (7 of 29, 4.6/100 patient-years) than with normal ventricular mass (7 of 111, 1.4/100 patient-years; p less than 0.01). Electrocardiography showed hypertrophy in too few patients to be of predictive value. Multiple logistic regression analysis showed that left ventricular mass index had the highest independent relative risk for future events and that systolic and diastolic pressures and age had slightly lower relative risks. In men with mild uncomplicated hypertension, left ventricular hypertrophy detected by echocardiography identifies patients at high risk for cardiovascular morbid events and is a significant risk factor for future morbid events independent of age, blood pressure, or resting ventricular function.

Standardization of M-mode echocardiographic left ventricular anatomic measurements

To improve standardization of echocardiographic left ventricular anatomic measurements, echographic left ventricular dimensions and mass were related to body size indexes, sex, age and blood pressure. Independent normal populations comprised 92 hospital-based subjects (64 women, 28 men) and 133 subjects from a population sample (55 women, 78 men). All measurements of chamber size, wall thickness and mass differed between men and women in both series (p less than 0.01 to p less than 0.001). Left ventricular mass was related most closely to body surface area among measurements of body size (r = 0.37, p less than 0.01 to r = 0.57, p less than 0.001) in all four groups. Indexation by body surface area eliminated sex differences in wall thicknesses and internal dimension, but a significant sex difference in left ventricular mass index persisted (89 +/- 21 g/m2 in men versus 69 + 19 g/m2 in women in the entire series, p less than 0.0001). The 97th percentile of left ventricular mass index was identical in both groups of men (136 and 132 g/m2) and women (112 and 109 g/m2). A highly significant difference in lean body mass, estimated from 24 hour urine creatine excretion, was observed between men and women (58 +/- 15 versus 40 +/- 13 kg, p less than 0.001) and no sex difference existed in left ventricular mass indexed by lean body mass (3.4 +/- 1.3 versus 3.5 +/- 1.5 g/kg). Weak correlations were observed between left ventricular mass/lean body mass and systolic or diastolic blood pressure (r = 0.25, p less than 0.05 and r = 0.28, p less than 0.01, respectively) but not age (18 to 72 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Improved sex-specific criteria of left ventricular hypertrophy for clinical and computer interpretation of electrocardiograms: validation with autopsy findings.

In a previous study of 543 patients we developed, using echocardiographic left ventricular mass as the reference standard, two new sets of criteria that improve the electrocardiographic diagnosis of left ventricular hypertrophy (LVH). One set of criteria, which is suitable for routine clinical use, detects LVH when the sum of voltage in RaVL + SV3 (Cornell voltage) exceeds 2.8 mV in men and 2.0 mV in women. The second set of criteria, suitable for use in interpretation of the computerized electrocardiogram, uses logistic regression models based on electrocardiographic and demographic variables with independent predictive value for LVH, with separate equations for patients in sinus rhythm and atrial fibrillation. To test these criteria prospectively with use of a different reference standard, antemortem electrocardiograms were compared with left ventricular muscle mass measured at autopsy in 135 patients. Sensitivity of standard Sokolow-Lyon voltage (SLV) criteria (SV1 + RV5 or RV6 greater than 3.5 mV) for LVH was only 22%, but specificity was 100%. The Cornell voltage criteria improved sensitivity to 42%, while maintaining high specificity at 96%. Higher sensitivity (62%) was achieved by use of the new regression criteria, with a specificity of 92%. Overall test accuracy was 60% for SLV criteria, 68% for the Cornell voltage criteria, and 77% for the new regression criteria (p less than .005 vs SLV). We conclude that the Cornell voltage criteria improve the sensitivity of the electrocardiogram for detection of LVH and are easily applicable in clinical practice.(ABSTRACT TRUNCATED AT 250 WORDS)

Midwall left ventricular mechanics : an independent predictor of cardiovascular risk in arterial hypertension

BACKGROUND An appreciable proportion of asymptomatic hypertensive patients have depressed left ventricular (LV) performance that is identified by midwall shortening/endsystolic stress relations but not by indexes that use endocardial shortening. It has not been established, however, whether depressed midwall ventricular performance has prognostic implications. METHODS AND RESULTS Echocardiographic endocardial and midwall LV fractional shortening/circumferential end-systolic stress relations in 294 hypertensive patients were analyzed as predictors of the occurrence of cardiovascular morbid events that occurred in 50 patients (including 14 deaths) during a 10-year mean follow-up. Patients with initially lower midwall but not endocardial shortening, either in absolute terms or as a percentage of predicted from observed end-systolic stress, were more likely to suffer morbid events than those with initially normal values (P < .004). Cardiovascular events occurred in 29 of 100 patients (29%) and death in 10 of 100 patients (10%) among those who were in both the two highest quartiles of LV mass index and the two lowest quartiles of midwall shortening, as opposed to 21 of 194 (11%) and 4 of 194 (2.1%) of the remaining patients (odds ratio, 3.4; 95% CI, 1.8 to 6.3; P < .0001; and odds ratio, 5.3; 95% CI, 1.6 to 17.3; P < .006, respectively). In logistic analysis, increasing age, high LV mass, high systolic blood pressure, and low values for an interaction term between LV mass index and midwall shortening independently predicted cardiovascular events (.04 < P < .001); increasing age, low midwall LV shortening as a percentage of predicted, and high value of the interaction term predicted the occurrence of cardiac death (.004 < P < .0002). Survival analysis controlling for age confirmed that low midwall shortening independently predicted cardiac morbidity or death, especially in the subgroup of patients with LV hypertrophy. CONCLUSIONS Depressed midwall shortening is a predictor of adverse outcome in arterial hypertension; the combination of higher LV mass and lower midwall shortening identifies individuals at markedly increased risk.

Percutaneous Left Atrial Appendage Occlusion for Patients in Atrial Fibrillation Suboptimal for Warfarin Therapy: 5-Year Results of the PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) Study

OBJECTIVES The aim of this study was to determine 5-year clinical status for patients treated with percutaneous left atrial appendage transcatheter occlusion with the PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) system. BACKGROUND Anticoagulation reduces thromboembolism among patients with nonvalvular atrial fibrillation (AF). However, warfarin is a challenging medication due to risks of inadequate anticoagulation and bleeding. Thus, PLAATO was evaluated as a treatment strategy for nonwarfarin candidate patients with AF at high risk for stroke. METHODS Sixty-four patients with permanent or paroxysmal AF participated in this observational, multicenter prospective study. Primary end points were: new major or minor stroke, cardiac or neurological death, myocardial infarction, or requirement for cardiovascular surgery related to the procedure within 1 month of the index procedure. Patients were followed for up to 5 years. RESULTS Thirty-day freedom from major adverse events rate was 98.4% (95% confidence interval: 90.89% to >99.99%). One patient, who did not receive a PLAATO implant, experienced 2 events within 30 days (cardiovascular surgery, death). Treatment success was 100% 1 month after device implantation. At 5-year follow-up, there were 7 deaths, 5 major strokes, 3 minor strokes, 1 cardiac tamponade requiring surgery, 1 probable cerebral hemorrhage/death, and 1 myocardial infarction. Only 1 event (cardiac tamponade) was adjudicated as related to the implant procedure. After up to 5 years of follow-up, the annualized stroke/transient ischemic attack (TIA) rate was 3.8%. The anticipated stroke/TIA rate (with the CHADS(2) scoring method) was 6.6%/year. CONCLUSIONS The PLAATO system is safe and effective. At 5-year follow-up the annualized stroke/TIA rate in our patients was 3.8%/year, less than predicted by the CHADS(2) scoring system.

Performance of primary and derived M-mode echocardiographic measurements for detection of left ventricular hypertrophy in necropsied subjects and in patients with systemic hypertension, mitral regurgitation and dilated cardiomyopathy☆

To determine which M-mode echocardiographic (echo) measurement best detects left ventricular (LV) hypertrophy, the sensitivity and specificity of upper normal limits of echo LV anatomic measurements (previously shown to have 97% specificity in living normal subjects) were tested in 60 necropsied patients with anatomic hypertrophy and in 28 necropsied patients with normal left ventricles. The prevalence of hypertrophy by each echo criterion was determined in 165 living patients with systemic hypertension, mitral regurgitation or dilated cardiomyopathy. The best separation between patients with normal vs increased necropsy LV mass was obtained using sex-specific echo LV mass index criteria (overall accuracy = 73 of 88 patients, 83%). Lower overall accuracies for separation of patients with and without hypertrophy were observed for echo cross-sectional area (59 of 88 patients, 67%; p less than 0.05 vs LV mass index) and indexes of LV wall thickness (39 to 51%, p less than 0.001). Among 113 living patients with moderate or severe hypertension, mitral regurgitation or dilated cardiomyopathy, LV mass index was increased in 73%, cross-sectional area index in 58% (p less than 0.02 vs LV mass index), and posterior wall thickness, septal thickness and relative wall thickness in only 11 to 32% (all p less than 0.001 vs LV mass index). Thus, an M-mode echo LV mass index of more than 134 g/m2 in men and more than 110 g/m2 in women detects concentric and eccentric LV hypertrophy accurately by comparison with necropsy and clinical reference standards; cross-sectional area is slightly less useful; and other M-mode echo criteria of LV hypertrophy perform too poorly to be clinically applicable.

Electrocardiographic detection of left ventricular hypertrophy using echocardiographic determination of left ventricular mass as the reference standard: Comparison of standard criteria, computer diagnosis and physician interpretation

Electrocardiographic findings of left ventricular hypertrophy were compared with echocardiographic left ventricular mass in 148 patients to assess performance of standard electrocardiographic criteria, the IBM Bonner program and physician interpretation. On echocardiography, 43% of the patients had left ventricular hypertrophy (left ventricular mass greater than 215 g). Sokolow-Lyon voltage-(S in V1 + R in V5 or V6) and Romhilt-Estes point score correlated modestly with left ventricular mass (r = 0.40, p less than 0.001 and r = 0.55, p less than 0.001, respectively). Sensitivity of Sokolow-Lyon voltage greater than 3.5 mV for left ventricular hypertrophy was only 22%, but specificity was 93%. Point score for probable left ventricular hypertrophy (greater than or equal to 4 points) had 48% sensitivity and 85% specificity, whereas definite hypertrophy (greater than or equal to 5 points) had 34% sensitivity and 98% specificity. Computer analysis resulted in 45% sensitivity and 83% specificity. Overall diagnostic accuracy of the IBM Bonner program (67%) was better than that of Sokolow-Lyon voltage (62%), but worse than the Romhilt-Estes point score (69% for greater than or equal to 4 points or 70% for greater than or equal to 5 points). Three cardiologists interpreted electrocardiograms independently and in a blinded fashion. Physician sensitivity was 56%, specificity 92% and accuracy 76%. Correlation with left ventricular hypertrophy was good (r = 0.70, p less than 0.001). It is concluded that: 1) computer diagnosis of left ventricular hypertrophy by the IBM Bonner program is no more accurate than diagnosis by Sokolow-Lyon or Romhilt-Estes criteria, and 2) physician recognition of left ventricular hypertrophy is more accurate.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular Care Facts: A Report From the National Cardiovascular Data Registry: 2011

OBJECTIVES The aim of this report was to characterize the patients, participating centers, and measures of quality of care and outcomes for 5 NCDR (National Cardiovascular Data Registry) programs: 1) ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry-GWTG (Get With The Guidelines) for acute coronary syndromes; 2) CathPCI Registry for coronary angiography and percutaneous coronary intervention; 3) CARE (Carotid Artery Revascularization and Endarterectomy) Registry for carotid revascularization; 4) ICD Registry for implantable cardioverter defibrillators; and the 5) PINNACLE (Practice INNovation And CLinical Excellence) Registry for outpatients with cardiovascular disease (CVD). BACKGROUND CVD is a leading cause of death and disability in the United States. The quality of care for patients with CVD is suboptimal. National registry programs, such as NCDR, permit assessments of the quality of care and outcomes for broad populations of patients with CVD. METHODS For the year 2011, we assessed for each of the 5 NCDR programs: 1) demographic and clinical characteristics of enrolled patients; 2) key characteristics of participating centers; 3) measures of processes of care; and 4) patient outcomes. For selected variables, we assessed trends over time. RESULTS In 2011 ACTION Registry-GWTG enrolled 119,967 patients in 567 hospitals; CathPCI enrolled 632,557 patients in 1,337 hospitals; CARE enrolled 4,934 patients in 130 hospitals; ICD enrolled 139,991 patients in 1,435 hospitals; and PINNACLE enrolled 249,198 patients (1,436,328 individual encounters) in 74 practices (1,222 individual providers). Data on performance metrics and outcomes, in some cases risk-adjusted with validated NCDR models, are presented. CONCLUSIONS The NCDR provides a unique opportunity to understand the characteristics of large populations of patients with CVD, the centers that provide their care, quality of care provided, and important patient outcomes.

Geometric determinants of electrocardiographic left ventricular hypertrophy.

Experimental studies have suggested that electrocardiographic recognition of left ventricular hypertrophy depends on geometric relationships involving wall thickness and chamber size. To determine the clinical significance of these observations, we studied the effects of echocardiographic LV mass (LVM), posterior wall thickness (PWT), interventricular septal thickness (IVST) and internal dimension (LVID) on ECG voltage in 360 patients. Standard voltage and nonvoltage manifestations ofLVH correlated modestly with LVM (r = 0.33–0.44, p < 0.001). Sokolow-Lyon precordial voltage (SLV) (SV, + RVs or V6) correlated moderately with LVM (r = 0.41, p < 0.001), but correlated less well with IVST (r = 0.26), PWT (r = 0.24) or LVID (r = 0.22). Stepwise regression revealed that there was no relation, independent of LVM, between SLV and IVST (r = - 0.03), PWT (r = 0.03) or LVID (r = 0.01). The 90 patients with increased LVM (> 215 g) but without LVH by SLV (false negatives) were compared with the 48 identified by SLV (true positives). False negatives differed from true positives in LVM (298 ± 72 vs 339 ± 98 g, p < 0.01), age (55 ± 18 vs 44 ± 19 years, p < 0.001), weight (70 ± 16 vs 63 ± 14 kg, p < 0.02), and distance from skin to the interventricular septum (42 ± 10 vs 38 ± 8 mm, p < 0.02). Thus, for a given LVM, ECG voltage criteria of LVH are independent of LV chamber dilatation or other geometric variables, but depend on age, weight and LV depth in the chest, suggesting that stratification of subjects by clinical variables has promise for improved electrocardiographic recognition of LVH.