BANGALORE, KARNATAKA.
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. / Name of the candidate and address
(in block letters) / Dr.SHILPA PATEL
NO 211, 9TH MAIN , HRBR LAYOUT,
KALYAN NAGAR 1ST BLOCK,
BANGALORE -560005
2. / Name of the Institution / KEMPEGOWDA INSTITUTE OF
MEDICAL SCIENCES,
BANGALORE.
3. / Course of study and subject / M.D. GENERAL MEDICINE
4. / Date of admission to the course / 31st MAY 2012
5. / Title of the topic / A CLINICAL STUDY ON CARDIOVASCULAR MANIFESTATIONS SECONDARY TO CIRRHOSIS OF LIVER
6.
/ BRIEF RESUME OF THE INTENDED WORK:
6.1INTRODUCTION
Cirrhosis is a very common ailment in India mostly caused by alcoholism & viral hepatitis.The clinical picture of patients with cirrhosis is dominated by the classicalcomplications such as ascites, bleeding from esophageal varices, portal hypertensionand encephalopathy. In addition, a considerable number of patients show signs ofperipheral vasodilatation with palmar erythema and reddish skin, raised and boundingpulse, and a low systemic blood pressure indicating a hyperdynamic circulation.Thehyperdynamic syndrome comprises an increased heart rate, cardiac output, andplasma volume, and a reduced systemic vascular resistance and arterial bloodpressure. Increased cardiac output in cirrhosis was described more than 50 years agoand a hyperdynamic, hyporeactive circulation is today a well-characterized element inthe clinical appearance of these patients.In addition, patients with cirrhosis developcomplications from a variety of organ damage including the heart, lungs, and kidneys, andother organ systems. Besides the hepatorenal syndrome, this has led to the recognitionof new clinical entities, such as cirrhotic cardiomyopathy and the hepatopulmonarysyndrome. Cirrhotic cardiomyopathy was initially thought to be of little clinicalrelevance. However, with the frequent use of invasive procedures like surgicalportocaval shunts, transjugular intrahepatic portosystemic shunt and livertransplantation, the adverse consequences of cardiac dysfunction became evident.These procedures put additional stress on the dysfunctional heart, precipitating overtcardiac failure. Unexpected deaths due to heart failure following these proceduresbecame a cause of concern in centres where these procedures were regularlyperformed.
6.2NEED FOR THE STUDY
Cirrhosis is associated with numerous cardiac abnormalities like increased cardiac output, left ventricular diastolic dysfunction, increased wall thickness of cardiac chambers, and pulmonary arterial hypertension. These concomitant cardiac abnormalities in patients with cirrhosis have been termed as ‘CIRRHOTIC CARDIOMYOPATHY’. Many complications can occur as a result of cirrhosis, out of which ascites, portal hypertension and varices are well-known. Many new complications are being recognized which include hepatopulmonary syndromes. The effects of cirrhosis on cardiovascular and circulatory system are not well studied
The use of new investigative modalities has shown several lines of evidence of impaired cardiac contractility and performance in patients with cirrhosis and has led to the introduction of the new clinical entity, CIRRHOTIC CARDIOMYOPATHY1.Cirrhotic Cardiomyopathy may be a major cause of morbidity and mortality inpatients with cirrhosis and liver transplant patients. With the advent of increased liver transplantation in India,this entity may have its impact on the transplantation success. The aim of the present study is to evaluate the cardiac abnormalities in patients with cirrhosis using ECG & 2 D Echocardiography to detect the occurrence of LVdysfunction,pulmonary hypertension,pericardial effusion and to assess thecontribution of cardiac dysfunction on mortality ,if any.
There is paucity of data from the Indian subcontinent on cirrhoticcardiomyopathy. Apart from a study by Jacob Alexander et al, there is scanty information on the status of cardiac abnormalities in Indian patients with cirrhosis.
6.3REVIEW OF LITERATURE
Until the late 1980s, the patient with liver cirrhosis was considered somehow “protected” against cardiovascular involvement due to the favorable pattern of themain ischemic risk factors (i.e. hypotension, hypolipidemia, low platelet count,impaired coagulation). Clear experimental and clinical evidence states that livercirrhosis is characterized by a sustained peripheral vasodilatation due to a wide number of vasoactive substances. The lowered systemic vascular resistance results in areduction of effective circulating plasma volume and blood pressure, and in anenhancement of heart rate, cardiac output and sympathetic tone (“hyperdynamic”circulation),with an eventual sustained reduction of cardiac after-load. Such acondition may be associated with an inconstant and often subclinical constellation ofcardiovascular abnormalities, such as resting tachycardia and baseline increasedcardiac output , reduced myocardial contractility with a blunted systo-diastolicresponse to inotropic and chronotropic stimuli , down-regulation of ß adrenergicreceptor function , histological changes , increase of brain natriuretic peptide (BNP)and serum troponin leading to impaired electric “recovery” ability of ventricularmyocardium .Taking into consideration the wide variability of these different aspects,a clinical entity has been recently recognized , known as “cirrhotic cardiomyopathy”(CC),term first introduced by Lee et al.1
In 1953 a study by Kowalski and Abelmann et al determined thatpatients with alcoholic cirrhosis have increased cardiac output and decreased arterialpressure and total peripheral resistance, i.e., hyper dynamic circulation. The basalcardiac output is increased, contractile function should, be normal as well.2
Regan et al studied ten alcoholics with no clinical evidence of cardiac disease,along with eight healthy controls, and intravenously infused both groups withangiotensin. Angiotensin is an eight-amino acid oligopeptide which is produced in thebody as part of the renin-angiotensin aldosterone system. Among other roles, it actson receptors in vascular tissue causing systemic arteriolar vasoconstriction, leading toincreased vascular resistance and thereby elevating cardiac after load. Afterangiotensin infusion, it was observed that although the left ventricular end diastolicpressure of the alcoholic group increased significantly more than the control group,the corresponding rise in stroke output and work was significantly less than thecontrols.This suggested a significantly attenuated Ventricular contractile response todiastolic filling. At that time, it was attributed to the chronic effects of alcoholtoxicity on the myocardium. 3
A similar result was noted shortly afterwards by Gouldet al, who examined the cardiac response to exercise of ten male subjects withevidence of chronic liver disease.At rest, increase in stroke index and cardiac outputof all participants were observed. With exercise, however, stroke index declineddespite elevations in left ventricular end diastolic pressure,(LVEDP) which representsa highly abnormal cardiac response.4
In 2003K.Mimidis et al. proved that QTc interval is prolonged in Child-Phug B and C cirrhotic patients independently of the etiology of cirrhosis. The reason for the same was not ascertained by the study. 5
Christos A et al studiedmyocardial dysfunction in patients with liver cirrhosis and serious hepatic failure remains unnoticed, since these patients exhibit a variety of more serious complications related to hepatic failure and portal hypertension. Morbidity and mortality rates increased in patients exhibiting cardiac symptoms. 6
A significant proportion of patients with cirrhosis affected by ascites, volume overload, and signs of hyperdynamic circulation have normal resting echocardiographic parameters but abnormal cardiac responses during exertion, stress, TIPS, or liver transplantation, consistent with the existence of a cirrhotic cardiomyopathy. Strict diagnostic criteria for cirrhotic cardiomyopathy are lacking, and this syndrome is often not recognized. Molecular basis for pathogenesis of cirrhotic cardiomyopathy and its early diagnosis for better outcome of patient was recognized by Enrico M. Zardi et al.in 2010.7
In 2011Ioana Mozos et al. studied the severity of liver disease, alcoholic etiology, and serum uric acid levels in patients, and it was found that all patients with liver cirrhosis had prolonged QTc interval. 8
7. / 6.4AIMS AND OBJECTIVES:
To determine the occurrence of cirrhotic cardiomyopathy among patients with cirrhosis of liver irrespective of etiology.
To evaluate QTc variation in cirrhotic patients with or without cirrhotic cardiomyopathy.
With special emphasis on correlation between the QTc variation and severity of cirrhosis.
______
MATERIALS AND METHODS:
7.1 SOURCE OF DATA:
All Inpatients in medical ward of KIMS hospital admitted during the period from 1st November 2012 to 30thApril 2014.
Type of Study : Comparitive study
Study Design: Purposeful sampling
Sample size:
60 (30 cases & 30 controls)
INCLUSION CRITERIA
- Age group >18yrs.
- Patients with clinical features and investigation suggestive of cirrhosis of liver.
Patients with suspected liver malignancy.
Patients with ischemic heart disease, valvular heart disease, conduction defects, cardiac failure and atrial fibrillation.
Patients already on medications which alter QTc like quinidine, Phenothiazine, TCA .
Known Hypertensive or Diabetic.
7.2 METHODS OF COLLECTION OF DATA:
All the patients admitted to KIMS hospital during the period of November2012 to April 2014,who are fitting into the inclusion criteria will be taken into the study.
All Study subjects will be selected from patients admitted in Kempegowda institute of medical sciences , Bangalore from November 2012 to April 2014 and full filling the inclusion and exclusion will be included in this study.
30 Cases will be selected on the basis of clinical presentation and investigation findings.
30 controls matched for age and sex willing to give informed consent will be included in the study.
Detailed history, clinical examination and necessary investigation will be done for both cases and controls.
Statistical method
Statistical data and variables obtained from the patients will be analyzed using student t test and Chi-square test.
7.3 Does the study require any investigations or interventions to be conducted on patients or other humans or animals?If so, please describe briefly.
YES (As and when required)
Hematology,Biochemistry-
Complete hemogram
serum electrolytes, RBS
Liver function tests
ECG, 2D ECHO
7.4 Has ethical clearance been obtained from ethical committee of your institution in case of 7.3?
YES, Clearance has been obtained from the ethical committee of KEMPEGOWDA INSTITUTE OF MEDICAL SCIENCES,BANGALORE.
7.5 DURATION OF STUDY: 18 months(November 2012 to April 2014).
8. / LIST OFREFERENCES
- Samuel S Lee & Soon Koo Baik et al. cirrhotic cardiomyopathy. Orphanet encyclopedia, January 2005.
- Kowalski HJ & Abelmann WH. The cardiac output at rest in Laennec’s cirrhosis.J Clin Invest 1953; 32(10): 1025-1033.
- Regan TJ, Levinson GE, Oldewurtel HA et al. Ventricular function in noncardiacswith alcoholic fatty liver: role of ethanol in the production of cardiomyopathy. JClin Invest 1969; 48(2): 397-407.
- Gould L, Shariff M, Zahir M & Di Lieto M. Cardiac hemodynamics in alcoholicpatients with chronic liver disease and a presystolic gallop. J Clin Invest 1969;48(5): 860-868
- K Mimidis,V Papadopoulos,K Thomopoulos et al. Prolongation of the QTc interval in patients with cirrhosis. Annals of Gastroenterology 2003;16(12): 155-158
- Christos A Fourlas et al. Cirrhotic Cardiomyopathy. Hellenic Journal Cardiology 2004;45:114-120
- Enrico M Zardi, Antonio Abbate et al. Cirrhotic Cardiomyopathy. Journal of AmericanCollege of Cardiology 2010; 56: 539-549.
- Ioana Mozos, Camelia Costea et al. Factors associated with a prolonged QT interval inliver cirrhosis patients. Journal of Electrocardiology 2011; 44: 105-108
9. / Signature of the candidate / DR. SHILPA PATEL
10. / Remarks of the guide / NEED TO IDENTIFY UNDERLYING CARDIOVASCULAR DISEASE WHICH CAN CONTRIBUTE TO SUDDEN DETERIORATION AND MORTALITY OF PATIENTS WITH CIRRHOSIS OF LIVER BUT WITHOUT THE USUAL COMPLICATIONS OF CIRRHOSIS CAUSING DEATH.
11. / 11.1 Name and Designation
Of the Guide / DR. K.P.BALRAJ
PROFESSOR
DEPT OF INTERNAL MEDICINE
KIMS, BANGALORE.
11.2 Signature
1.3 Head of the Department / DR. M.V.POORNACHANDRA
PROFESSOR AND HEAD OF THE DEPARTMENT,
DEPARTMENT OF INTERNAL MEDICINE
KIMS, BANGALORE
11.4 Signature
12. / 12.1 Remarks of the Principal
12.2 Signature
1