The Non Mortality of Hypertrophic Cardiomyopathy in an ...

JOURNAL OF INSURANCE MEDICINE Copyright ? 1996 By Journal of Insurance Medicine

Vol. 28, No. 1 1996

The Non Mortality of Hypertrophic

Cardiomyopathy in an Unselected, Community Diagnosed and Treated Population

John R. Iacovino, MD Vice President-Medical Director New York Life Insurance Company

ABSTRACT

Hypertrophic Cardiomyopathy (HC) is portrayed in past literature as having an ominous prognosis. However, most studies emanated from medical centers and suffered from potential referral bias.

A population based, community diagnosed and treated survival study is analyzed by the life table method. Despite potential causes for both underestimation of the observed mortality as well as for overestimation of expected mortality, the study appears to reveal a more favorable prognosis for HC in this population.

A study of individuals with a cardiac impairment whose observed survival exceeds expected survival is unusual. When previous literature indicates the impairment has a two to six percent annual mortality, the results become sensational. A ten-year follow-up of community diagnosed and treated patients with hypertrophic cardiomyopathy (HC) is reviewed with a life table analysis.1

The value of an article for a mortality abstract depends upon many factors. Two of the most important are 1) number of observed deaths and 2) existing mortality sources. Thirty-seven entrants experiencing eight deaths over a ten year period is very lean. However, existing mortality abstracts on an unselected, community based study of HC are nil. By the evaluation grades proposed by Singer and Kita ~ this article would rate between an A (highest value) and B (intermediate value).

Study subjects were identified through the

Rochester Epidemiology Project. This provides a valu-

able database for large scale, population-based inves-

tigations of the natural histories of diseases. This

resource afforded nearly complete ascertainment of

clinically diagnosed cases, of HC in the population and

provided a reliable basis for follow-up. The study

period was 1976 through 1990.

Patients were diagnosed to have HC (obstructive,

nonobstructive or apical) on the basis of clinical and

echocardiographic findings. Echocardiographic diag-

nosis required the presence of asymmetrical septal

hypertrophy (septal-to-free-wall ratio of equal to or

greater than 1.3) and a .nondilated left ventricle with

normal or hyperdynamic function or concentric hyper-

trophy with features of outflow tract obstruction.

Thirty-seven Olmsted County, Minnesota resi-

dents were diagnosed during life with HC. Eight died

during the ten year period of observation; two of car-

diac and six of noncardiac causes. No withdrawals

were noted. Mean age was 59 years; 57% were female.

The most common presenting symptoms were:

? Palpitations

45%

? Chest pain

43%

? Dyspnea

16%

? Syncope

11%

Laboratory and physical examination revealed:

? Systolic murmur

89%

? Left ventricular hypertrophy on ECG 38%

? Cardiomegaly on chest x-ray

24%

On echocardiography, the most common pattern

was asymmetrical septal hypertrophy in 46%.

Seventy-five percent had an average left ventricular

outflow gradient of 39 mmHg. Mean left ventricular

septal diastolic thickness was 17.5mm and mean left

ventricular free wall thickness was 12mm.

Ambulatory 24 hour electrocardiographic moni-

toring was done in 54%. All were in sinus rhythm

except two who had wandering atrial pacemaker. One-

51

VOLUME 28 NUMBER 1 1996

JOURNAL OF INSURANCE MEDICINE

third had complex ventricular ectopy (ventricular premature complexes >700/hour in pairs or bigeminy).

Median follow up was 7.6 years. Among patients who presented with class I symptoms, 43% progressed to class II, 11I or IV. No patient had a myectomy. Fourteen percent had at least one syncopal episode. Of the two cardiac deaths, one was sudden. Two other enrollees suffered cardiac arrest, survived, and had automatic, implantable cardiac defibrillators inserted. Their duration of follow-up was not noted.

The article reviewed the natural history of HC in an unselected, community setting. The annual risk of cardiac death was 0.7%. This strongly contrasts with the two to six percent annual mortality risk previously reported. The authors noted 50% of previously published studies on HC came from two centers, thus referral bias was an important element likely reflecting more advanced disease. The mean ages of participants from two of these studies were 39 and 43 years. This contrasts with the mean age of 59 in this study reflecting the age distribution of unselected, community diagnosed patients. The younger ages likely represent those with progressive, advanced disease referred to medical centers. The authors hypothesize that HC in the elderly may be a disease distinctly different from that which exists in the young.

The authors believe very few, if any, cases of HC were missed in Oimsted County residents. However, the compounding factor of under diagnosis cannot be dismissed. Two young men who experienced sudden death were reported at autopsy to have HC. Thus, this excellent result could represent a more stable subgroup previously selected by sudden death and medical care.

Data Calculations:

The article illustrated survival plots with expected and observed survival percents at two, four, six, eight and ten years. The figure (originally 2.5 x 5 cm) was enlarged approximately six times to facilitate measurement of survival percents at each time interval. The enlargement process potentially creates distortion and inaccuracies in measurement of both expected and observed survival percents. Although the illustrated expected survival plot was linear after enlargement, the measurement and calculation of interval expected survival percents was not linear. These expected survival results were not graduated or tested for smoothness since both expected and observed measurements were potentially equally distorted at each time interval.

The authors derived expected mortality from age and sex matched United States white population tables. I do not believe this is an appropriate expected mortality table; the reason will be discussed later in this analysis.

Survival percents, expected and observed, were extrapolated from caliper measurements in millimeters from the closest baseline percent. One millimeter equaled 0.625% which was rounded to 0.63%. Further rounding of survival percents to the nearest 0.1% was appropriate due to the potential inaccuracies of measurement described. Definitions of abbreviations used in the life table text and analysis are shown in table 1. Single decrement mortality tables (tables 2 and 3) were created from the expected and observed survival percents. Interval rates were rounded to three decimal places. Observed and expected deaths were rounded to the nearest whole number.

Comparative mortality (table 4) was calculated from expected and observed mortality tables. The EDR was calculated from (1000) q-q'. The mortality ratio was calculated from q divided by q'.

Discussion:

Each two year observed interval as well as the entire ten year follow-up period had a better survival than expected. All excess death ratVesVare negati?ve and all mortality ratios are less thanv1o00 Yo. Thisvis a rather surprising result for an impairment that carries an ominous prognosis in the medical literature. An unimpaired population should not have a better survival than expected. It is unreasonable to believe HC confers a survival benefit.

Several reasons for the unexpected outcome are possible. As previously noted, enlargement of survival plots can produce distortion and inaccuracies in measurement. However, direct inspection of the published survival curve shows observed survival to be better than or nearly equal to expected survival in all intervals. The most likely explanation for this illogical result is the author's expected mortality table, the United States white population. My suspicion is Olmsted County, Minnesota is not typical of the United States white population. Olmsted County is located in Southeastern Minnesota and has a population of about 106,500. Rochester with the Mayo Clinic is the County Seat. Olmsted County may not represent the United States white population table from a socioeconomic/mortality standpoint. Overall, I suspect Olmsted County's mortality is more similar to an

52

JOURNAL OF INSURANCE MEDICINE

VOLUME 28 NUMBER 1 1996

Table 1: Oefinitions of Abbreviations Used in the Text and Mortality Tables

Cumulative Survival Rate p - Interval Survival Rate q - Interval Mortality Rate

Number of Living Entrants d - Number of Deaths

V

qFDI~- EGxecoemsestrDiceaAtvhe,rRagateeApnenruTahloMuosratnadlitpyeRraYteear

vv,

(Calculated from geometric average annual mortality rate (1000), q-q

MR - Mortality Ratio (Calculated from geometric average annual mortality rate

V V,

(100) (q/q)

insurance industry aggregate or ultimate mortality table than to a United States white population table. If my assumption is correct, expected survival would be higher, expected mortality lower. Necessarily, the expected geometric average annual mortality rate would diminish thus increasing the difference between observed and expected rates. The net effect could be positive EDRs and mortality ratios greater than 100%; the overall mortality of HC would be increased. Nevertheless, the mortality of HC in this study appears much better than previously reported.

Whether the observed mortality of HC is under or overestimated by this study is unknown. Since only two individuals out of the eight deaths suffered a cardiac death, the true mortality could be overestimated. Underestimation is strongly supported by several factors. Two enrollees suffered cardiac arrest and were surviving with implantable cardiac defibrillators. Additionally, two individuals not included in analysis were discovered at autopsy to have HC. Finally, a mean follow up of 7.6 years is short and provides just a snapshot of the spectrum of potential mortality. Forty-three percent of patients who presented with Class I symptoms had progressed to more symptomatic Classes II, III and IV. A 59 year old cohort matched for sex has a 22 year life expectancy by 1992 United States white population tables. Comparative mortality reveals a dramatic increase in the EDR (although still negative) over the final two, two year intervals. Whether this indicates future trending of the EDR toward positive is suggestive but hypothetical. Hopefully the authors will update the survival

study at five year intervals to accurately ascertain the long term mortality trend of this community based population with HC.

Despite the short duration and methodologic questions, this study is highly useful as it depicts an unselected, community population. HC does not appear to be the ominous impairment portrayed in most referral center based studies. The results of those studies are currently reflected in companies medical underwriting impairment manuals. How much more liberal we can be in our underwriting of HC.depends upon the physiologic characteristics as well as the duration of stability or rapidity of progression of the individual case, plus the wisdom (or foolishness) of the Medical Director and underwriting policies of their Company.

53

VOLUME 28 NUMBER 1 1996

References

1 Cannan CR, Reeder GS, Bailey KR et al. The Natural History of Hypertrophic Cardiomyopathy, A Population-Base Study, 1976 through 1990. Circulation 1995; 92: 2488-2495.

2 Singer RB, Kita MW. Guidelines for Evaluation of Follow-up Articles and Preparation of Mortality Abstracts. J Insurance Med 1991; 23, #1: 21-30.

JOURNAL OF INSURANCE MEDICINE

Years

P'

p'

q'

?

I

d

q,

p,

p,

q,

0-2

93.9

.939

.061

1000

61

.561

.939

93.9

.031

3-4

88.8

.946

.054

939

51

.054

.046

88.8

.028

5-6

83.2

.937

.063

888

56

.063

.937

83~

7-8

75.8

.911

.089

832

74

.089

.911

75.8

.048

0-10

70.t

.925

.075

758

57

.075

.925

70.1

.038

0-10

70.1

.701

.299

1000

299

.299

.701

70.1

.03S

?

Years

P

p

q

I

d

q

P

P

q

0-2

93.9

.939

3)61

37

2

.054

.946

94.6

.027

3-4

91.3

.972

.028

35

1

.029

.971

91.9

.014

5-6

91.3

1.0

0

34

0

0

1.0

91.9

0

7-8

82.5

.904

.096

34

3

.088

.912

83.8

.045

9-10

75.8

.919

.081

31

2

.065

.935

78.4

.033

0.10

75.8

.758

.242

37

8

.216

.754

78.4

.024

0-2

. -4

87%

3-4

-14

50%

,56

-32

0%

7-8

-1

98%

9-10

-5

87%

0-10

-11

69%

54

 ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download